Terapie a podpůrné vlivy

Jodid draselný + vitamín B17 (kyanidy)

• Proč a jak funguje "Nevíš-li co dáti, dej kalium iodati"

• Práce ukazuje učinnost KI a k. hypothiokyanové na jehnětem infikovaných RSViry
• Měří koncentrace účinných látek na buněčnáých liních s RS viry
• A následně podrobně popisuje podání dospělým dobrovolníkům s prokázáním účinných koncentrací na sliznici
• Popsané je i dávkování
• Tahle práce mne motivovala k požití 65 mg a následně 135 mg jodidu draselného v podobě radiační tablety v době kovidové
• A zbavila mne začínající virozy a chronického pokašlávání
• Fungovalo při covid19, bude fungovat i na RS virozy aj.
• Roztoky na bazi jodu byly i jednou z nejúčinnějších terapií Španělské chřipky
• jod je nejužívanější desinfekcí v medicíně vůbec...

Acetate

• Circulating acetate comes from three distinct sources:
• Endogenous acetogenesis from acetyl-CoA hydrolysis,
• Exogenous acetate from the diet (e.g., vinegar, ethanol, fermented foods, etc.),
• Acetogenesis from gut bacteria

• Resistance to infection increased when the microbiota produced more short-chain fatty acids, especially acetate

In vitro

• Cells were treated with this acetate also produced promising results.

• High-fiber diet protects mice from RSV infection
• Dependent on intestinal microbiota and production of acetate
• Oral administration of acetate
• Mediated interferon-beta (IFN-beta) response
•  by increasing expression of interferon-stimulated genes in the lung
• Associated with reduction of viral load
• Pulmonary inflammation in RSV-infected mice
• 1 IFN signaling via the IFN-1 receptor (IFNAR) was essential for acetate antiviral activity in pulmonary epithelial cell lines and for the acetate protective effect in RSV-infected mice.

• Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response

• Short-chain fatty acid acetate triggers antiviral response mediated by RIG-I in cells from infants with respiratory syncytial virus bronchiolitis

Aglaia (A. ignea, A. duppereana, A. cucculata, A. euphoroides and A. tsangii)

• Exhibited selective anti-RSV activity
• IgnT1 (dammarenolic acid),
• DupT1 (aglaiol)
• CucT1 (niloticin)
• Both ignT1 and dupT1 inhibit RSV replication at a post-entry stage
• IgnT1 being significantly more potent than dupT1.
• Inhibitors possibly target the viral replicative enzyme, the RNA polymerase.
• IgnT1 demonstrated favorable cellular safety
• Plant derived diterpenoid compound (aphidicolin)
• Concentration used about twice as cytotoxic as ignT1
• While demonstrating virtually no anti-RSV activity.
• Ribavarin exhibits much more toxicity resulting from its effect on cellular RNA and DNA polymerases
• (Lafeuillade et al. 2001; Prince 2001; Seetharama and Narayana 2005)
• Methylation of ignT1
• Resulted in a complete loss of anti-RSV as well as cytotoxicity
• Remarkable loss of activity could be related to an interaction of the polar carboxylic group of dammarenolic acid with a potential target molecule of the virus
• Anti-RSV compounds from Aglaia species present useful sources of lead compounds against RSV
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

Anemarrhena asphodeloides

• Rhizomes of Anemarrhena asphodeloides Bunge (Liliaceae)
• Traditional medicine for anti-diabetic, anti-phlogistic, anti-pyretic, asthma, cough, bronchitis, allergy, sedative, diuretic, and anodyne properties in Korea, China, and Japan (Duke et al., 2002).
• Include xanthones (Pardo-Andreu et al., 2006),
• Norlignans (Iida et al., 2000; Park et al., 2003; Lim et al., 2009),
• Steroidal saponins (Nakashima et al., 1993; Sy et al., 2008; Ren et al., 2006; Wang et al., 2010),
• Anti-diabetic (Nakashima et al., 1993),
• Anti-cancer (Sy et al., 2008),
• Anti-oxidant (Pardo-Andreu et al., 2006),
• Anti-fungal (Iida et al., 2000; Park et al., 2003),
• Anti-depressant (Ren et al., 2006),
• Anti-inflammatory (Lim et al., 2009)
• Neuroprotective effects (Wang et al., 2010).
• Nyasol and its derivatives isolated from the ethyl acetate fraction of A. asphodeloides rhizomes had potent RSV inhibitory potential
• (IC50= 0.39 to 0.89 µM) (Bae et al., 2007)
• Three known phenolic compounds
• (-)-(R)-nyasol (=4,4’-(1Z,3R)-Penta-1,4-diene-1,3 diyldiphenol; 1),
• Its derivative (-)-(R)-4’-O-methylnyasol (2),
• Broussonin A (3)
• Isolated from the rhizomes of Anemarrhena asphodeloides
• Identified as the active principles capable of efficient respiratory syncytial virus (RSV) inhibition
• Novel inhibitors of plant origin against the RSV-A2 strain propagated in HEp-2 cells
• Two steroidal saponins
• Two xanthone derivatives from the butanol extract of the rhizomes of A. asphodeloides
• Timosaponin A-III (1) (Kawasaki et al., 1963),
• Anemarsaponin B (2) (Dong et al., 1991),
• Mangiferin (3) (Qin et al., 2008),
• Neomangiferin (4) (Qin et al., 2008)
• Timosaponin A-III exhibited potential anti-viral activity against the RSV-A2
• In HEp-2 cells, with an IC50 of 1.00 µM
• More potent than the positive control, ribavirin (IC50 = 1.15 µM)
• Anemarsaponin B (2) were inactive (IC50 > 5 µM)
• Spirostane skeleton (1) is more active than the furostanol structure (2) in the steroidal saponins
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

Antileukotrieny

• Preventivně nebo léčebně, mělo spíše příznivý účinek, jednoznačné důkazy však opět chybějí.
• www.ipvz.cz/seznam-souboru/7327-kapitoly-z-detske-pneumologie.pdf

RSV infection significantly decreased airway antioxidant system

• SOD,
• Catalase,
• Glutathione S-transferase,
• Glutathione peroxidase
• In murine lungs
• In the airways of children with severe bronchiolitis
• Markers of oxidative damage correlated with severity of clinical illness in RSV-infected infants
• Nrf2 expression was also significantly reduced
• In the lungs of viral-infected mice.
• RSV infection induces significant down-regulation of the airway antioxidant system in vivo
• Resulting in lung oxidative damage
• Modulation of oxidative stress may pave the way toward important advances in the therapeutic approach of RSV-induced acute lung disease.
• www.atsjournals.org/doi/full/10.1164/rccm.201010-1755OC

Apigenin (flavonoid aglycone) and acacetin glycosides

• Showed weak to moderate activity against human RSV Long strain
• www.ncbi.nlm.nih.gov/pmc/articles/PMC7129285/

Arbidol

• Half of the concentration of hydrochloric acid toxicity (TD50) 85.39 L,
• When the drug concentration of 25 L, anti-viral drugs biosynthesis Group, a direct role in drug group.
• Anti-drug adsorption 4 h, 8 h adsorption antiviral drugs inhibit the virus could reach 81.61% respectively.
• 79.57%. 78.60%.4 the drug group were 40.39% and 50% effective concentration (ED50) 11.52. 8.74,25.36 L and 10.40.
• Arbidol hydrochloric acid can inhibit the in vitro effect of the CPE RSV,
• Virus inhibition rate increased with increasing concentration of the drug, through various channels, Arbidol hydrochloride play the role of anti-RSV.
• www.arbidol.org/rsv.html#rsv1

Astragalus polysaccharide

• Respiratory syncytial virus induced lung infection in young mice

Male 3-week-old BALB/c mice + Astragalus polysaccharide (APS)

• Medium and high groups were given 100, 200 and 300 mg/(kg.d) APS by gavage once a day for 5 days;
• Ribavirin group were given 46 mg/(kg.d) ribavirin by gavage once a day for 5 days.
• Mice in control group and RSV group were given equal volume of normal saline by gavage
• Results
• APS medium- and high-dose groups and ribavirin group could reverse the above changes
• APS could inhibit RSV replication, regulate immune response, reduce inflammation and oxidative reaction induced by RSV
• Effect may be related to the inhibition of TLR4/MAPK/NF-?B pathway activation.

• 10.11855/j.issn.0577-7402.2022.04.0340
• www.plamj.org/index.php/plamj/article/view/2633

Erythrina abbysinica bark

• Stem bark of E. abbysinica
• Identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles
• Importance in topical treatment of these infections
• E. abyssinica extract for treatment of respiratory infections.
• www.researchgate.net/publication/359265672_Anti-respiratory_syncytial_virus_and_anti-herpes_simplex_virus_activity_of_six_Tanzanian_medicinal_plants_with_extended_studies_of_Erythrina_abyssinica_stem_bark

A single, low dose of a cGMP recombinant BCG vaccine

• Elicits protective T cell immunity against the human respiratory syncytial virus infection and prevents lung pathology in mice
• HRSV causes year-to-year outbreaks of disease, which also affects the elderly and immunocompromised adults.
• Recombinant Bacillus Calmette-Guerin (BCG) vaccine expressing the nucleoprotein (N) of hRSV formulated under current good manufacture practices (cGMP rBCG-N-hRSV)
• Confers protective immunity to the virus in mice
• Single dose of the GMP rBCG-N-hRSV vaccine retains its capacity to protect mice against a challenge with a disease-causing infection of 1×107 plaque-forming units (PFUs) of the hRSV A2 clinical strain 13018-8.
• Vaccinated mice displayed reduced weight loss and less infiltration of neutrophils within the airways
• Reduced viral loads in bronchoalveolar lavages
• Re-stimulation of splenic T cells at 28days post-immunization activated a repertoire of T cells secreting IFN-? and IL-17, which further suggest that the rBCG-N-hRSV vaccine induced a mixed, CD8+ and CD4+ T cell response capable of both restraining viral spread and preventing damage of the lungs.
• All these features support the notion that rBCG-N-hRSV is a promising candidate vaccine to be used in humans to prevent the disease caused by hRSV in the susceptible population.
• pubmed.ncbi.nlm.nih.gov/28065474/

Adina piluUfera, Narcissus tazetta and Wikstroemia indica

• Against Respiratory Syncytial Virus
• A purified compound from Wikstroemia indica, designated as daphnoretin
• Lectin purified from Narcissus tazetta var. chinensis, designated as NTL
• Ethanol extract of Adina pilulifera
• Possess potent antiviral activity and low cytotoxicity
• Ethanol extract of pilulifera was further fractionated and the ethyl acetate fraction was found as the most potent anti-RSV fraction.
• The three candidates were shownto possess anti-RSV activity and have different modes of action.
• core.ac.uk/download/pdf/48547682.pdf

Caesalpinia minax Hance

• A member of the Caesalpinia genus
• Prickly shrub growing in the tropics and subtropics
• Seeds of this plant, which is called ‘ku-shi-lian’
• Chinese folk medicine for the treatment of common cold, fever and dysentery (Jiangsu New Medical College, 1977). Jiang et al. (2001) working with the

Chloroform fraction of the ethanol (95%) extract of the seeds

• In vitro anti-RSV activity
• Isolation of a novel rearranged vouacapane diterpenoid spirocaesalmin
• Spirocaesalmin
• Significant activity against respiratory syncytial virus
• IC50 = 19.5 ± 1.5 ug mL, TC50 = 126.9 ± 2.0 ug ml and SI= 6.5) in cell culture
• Corresponding values for the positive control (ribavirin) are 3.6 ± 0.2 ug ml, 62.5 ± 1.9 ug ml and 17.4, respectively. Thus isolation of spirocaesalmin
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

Carvacol - CAVE :-( !!!

Balb/c mice were infected by intranasal inoculation of RSV-A2

• Treatment started daily 24 h after infection
• Sacrificed on day five after infection
• Results showed that using carvacrol enhanced immune cell influx, cytokine/chemokine production, and virus titer, and aggravated lung pathology.
• Our result showed that carvacrol administration increased viral titer compared to the RSV-PBS group.
• Carvacrol significantly induced IFN-gamma production
• And did not induce IL-10 production.
• Carvacrol non-significantly increased lymphocytes and monocytes count
• But did not affect the neutrophil count.
• Carvacrol at the concentration of 80 (mg/kg)
• Did not show immunomodulatory activity to alleviate the RSV infection outcome
• Many herbal remedies in use contain carvacrol.
• ijm.tums.ac.ir/index.php/ijm/article/view/2939

RSV infekce protokol terapie dle FL CCC Aliance

Nasal spray: 2-3 times a day

1% povidone-iodine

• Potent inhibitors of SARS-CoV-2 and influenza virus
• Dramatically alter the course of infections with these viruses

Iota-Carrageenan

• Potent inhibitors of SARS-CoV-2 and influenza virus
• Dramatically alter the course of infections with these viruses

Nasal irrigations with saline

• May also be of some benefit

Neutral electrolyzed water

• May also be of some benefit

Mnou dodaná česká specialita - Actimaris a Ozoil a stříbro

Mouthwash: 2-3 times daily

Antiseptic-antimicrobial mouthwashes

• Shown to inhibit replication of multiple respiratory viruses, including influenza and RSV.
• We recommend products containing
• Chlorhexidine

• Povidone-iodine,
• Cetylpyridinium chloride
• Scope™, Act™, Crest™,
• Combination of eucalyptus, menthol, and thymol (e.g., Listerine™)

• Nebo opět u nás: Jox spray ( pozor, trochu pálí)

Elderberry

• 4 times daily, according to manufacturer’s dosing guidelines

Vitamin C

• 500-1000 mg, 4 times daily
• Vitamin C has important anti-inflammatory, antioxidant, and immune-enhancing properties, including increased synthesis of type I interferons
• Effects of Vitamin C on the course of upper respiratory tract infections have long been recognized

Nitazoxanide (NTZ)

• 500 mg, 2 times daily
• Oral antiparasitic drug, has activity against many protozoa and helminths
• Antiviral, anti-inflammatory, and immune-modulatory effects
• Broad spectrum antiviral activity that includes influenza virus, RSV, and SARS-CoV-2.

Ivermectin

• 0.4 mg/kg for 5 days
• In-vitro (test tube) studies suggest that ivermectin has broad antiviral activity against RNA viruses including influenza.
• However, there is no (published) clinical data on the use of ivermectin in the treatment of influenza.
• Therefore, we recommend ivermectin as part of a multi-drug regimen when nitazoxanide is not available.
• Ivermectin is best taken with a meal.
• This drug should be avoided in pregnancy and in patients taking calcineurin inhibitors (cyclosporine and Prograf).

Zinc

• 50-90 mg daily
• Essential for innate and adaptive immunity, with zinc deficiency being a major risk factor for influenza.
• Due to competitive binding with the same gut transporter, prolonged high-dose zinc (> 50mg day) should be avoided, as this is associated with copper deficiency.

N-acetylcysteine (NAC)

• 600-1200 mg orally, 2 times daily
• NAC, the precursor of reduced glutathione, penetrates cells where it is deacetylated to yield L-cysteine, thereby promoting glutathione (GSH) synthesis.

Sunlight and photobiomodulation (PBM): 30 minutes daily

• PBM is also known as low-level light therapy, red light therapy, and near-infrared light therapy.
• Acting as a mitochondrial stimulant and increasing ATP production.

Melatonin

• 5-10 mg nightly
• Potent antioxidant with important anti-inflammatory effects.

Symptomatic treatments

• Acetaminophen, antihistamines, and a decongestant
• covid19criticalcare.com/treatment-protocols/flu-rsv-treatment/

Cimicifuga foetida L. - PLOŠTIČNÍK SMRDUTÝ - Shengma (šeng-ma)

• Inhibited human respiratory syncytial virus in HEp-2 and A549 cell lines
• Sheng-Ma-Ge-Gen-Tang (SMGGT; Shoma-kakkon-to) has been proven to be effective at inhibiting HRSV-induced plaque formation
• Cimicifuga foetida is the major constituent of SMGGT
• Effectively inhibited the cytopathic effects of HRSV by a plaque reduction assay in both human upper (HEp2) and lower (A549) respiratory tract cell lines.
• Foetida dose-dependently inhibited HRSV-induced plaque formation (p < 0.0001)
• Before and after viral inoculation,
• Especially in A549 cells (p < 0.0001).
• C. foetida dose-dependently inhibited viral attachment (p < 0.0001) and could increase heparins effect on viral attachment.
• Time-dependently and dose-dependently (p < 0.0001) inhibited HRSV internalization.
• C. foetida could stimulate epithelial cells to secrete IFN-beta
• To counteract viral infection
• Did not stimulate TNF-alpha secretion
• Could be useful in managing HRSV infection
• pubmed.ncbi.nlm.nih.gov/22298455/

• Antiviral effect of cimicifugin from Cimicifuga foetida against human respiratory syncytial virus.

• Wang KC, Chang JS, Lin LT, Chiang LC, Lin CC. Am J Chin Med. 2012;40(5):1033-45. doi: 10.1142/S0192415X12500760. PMID: 22928833

Cinnamomum cassia Blume

• Water extract of Cinnamomum cassia Blume
• Inhibited human respiratory syncytial virus
• By preventing viral attachment, internalization, and syncytium formation
• pubmed.ncbi.nlm.nih.gov/23518419/

Cinnamomi Cortex

• Through interaction with G glycoprotein
• assets.researchsquare.com/files/rs-262616/v1/f7a67d5d-284b-4ddb-a445-6441988ed293.pdf?c=1646848111

Clove extract

• Results Out of several plants examined only clove extract showed anti-RSV activity.
• Inhibiting RSV infection of HEp-2 cells with
• IC50 value of 102 ug/ml and reducing
• At 2000 µg/ml, the viral yield by ~10000 times
• Activity was highly selective for RSV
• Directly targeted the free RSV particles infectivity during early step of viral infections.
• Conclusions Clove extract showed a potent anti-RSV activity that appeared to be virucidal.
• Further extension of these studies is warranted
• gupea.ub.gu.se/handle/2077/64155

Coconut oil

Lauric acid

• Accounts for much of the reported antiviral activity of coconut oil

Capric acid (C10) and monocaprin

• Have also shown promising activity against other viruses, such as HIV-1 (Kristmundsdóttir et al., 1999).
• Capric acid accounts for about 7% of coconut oil.
• Hilarsson and co-workers (2007) against respiratory syncytial virus (RSV)
• Most active compound tested was monocaprin (C10)
• Which also showed activity against influenza A virus and significant virucidal activities even at a concentration as low as 0.06-0.12%.
• 2012.ateneo.edu/ls/sose/sose/news/research/potential-coconut-oil-and-its-derivatives-effective-and-safe-antiviral

• Hilmarsson H, Traustason BS, Kristmundsdóttir T, Thormar H. Virucidal activities of medium- and long-chain fatty alcohols and lipids against respiratory syncytial virus and parainfluenza virus type 2: comparison at different pH levels. Archives of Virology 2007: 152(12):2225-36.

Dietary bovine colostrum

• Exerts the effects to inhibit hRSV
• Ameliorate the symptom by hRSV infection,
• Enhances the CD8 T cell response during the hRSV infection.
• www.researchgate.net/publication/281303291_The_effect_of_dietary_bovine_colostrum_on_respiratory_syncytial_virus_infection_and_immune_responses_following_the_infection_in_the_mouse
• journals.sagepub.com/doi/full/10.1177/0890334420988239

Coptidis Rhizoma extract

• Inhibits replication of respiratory syncytial virus in vitro and in vivo
• By inducing antiviral state
• Coptidis Rhizoma is derived from the dried rhizome of Ranunculaceous plants
• And is a commonly used traditional Chinese medicine

Against RSV in human respiratory tract cell line (HEp2) and BALB/c mice

• Effective dose of CRE significantly reduces the replication of RSV in HEp2 cells
• And reduces the RSV-induced cell death
• Through the induction of type I interferon-related signaling
• Antiviral state in HEp2 cells

Oral administration of CRE in BALB/c mice against RSV

• Prophylactic effects

• Presence of several compounds in the aqueous fraction and among them
• Palmatine was related to the antiviral properties and immunemodulation effect
• Could be a potential source as promising natural antivirals that can confer protection to RSV.
• pubmed.ncbi.nlm.nih.gov/28551874/

Cordiceps

• patents.google.com/patent/CN104274497B/en

Cryptoporus volvatus

• CM-H-L-5
• 5alpha,8alpha-epidioxy-22E-ergosta-6,22-dien-3ß-ol
• Were isolated from the Cryptoporus volvatus

antiviral experiment in vitro

• Had anti-PRRSV activity (proti prasecimu RS viru)

water extract of Cryptoporus volvatus fruiting bodies in vivo and in vitro

• Effective antiviral effect on PRRSV infection.
• Inhibited the entry of PRRSV and the synthesis of PRRSV RNA, a
• Could inhibit the replication of the virus in vivo.
• The survival rate of pigs was improved
• www.mdpi.com/1420-3049/27/14/4457

Curcumin ([1E,6E]-1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione)

• Spice turmeric
• Demonstrated the effects of preinfection curcumin treatment on preventing RSV replication in human nasal epithelial cells with little cytotoxicity
• There was minimal effect on lung epithelial cells
• curcumin would work best as a preventative therapy to lessen disease acquisition and severity
• www.dovepress.com/respiratory-syncytial-virus-current-and-emerging-treatment-options-peer-reviewed-fulltext-article-CEOR

Cyclopiazonic acid

• An inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus
• Cyclopiazonic acid (CPA), an intracellular calcium ATPase inhibitor
• As a RSV inhibitor (EC50 values 4.13 uM) by screening of natural product library
• CPA inhibited the replication of RSV strains belonging to both A and B subgroups and human parainfluenza virus type 3, but not Enterovirus 71.
• calcium ATPase inhibitors (Thapsigargin and BHQ) and calcium ionophores (A23187 and ionomycin), but not calcium channel blockers (nifedipine, nimodipine, and tetrandrine)
• Also had similar effect
• Increase in intracellular calcium concentration is detrimental to RSV replication
• New strategy for anti-RSV therapy via increasing intracellular calcium concentration
• Takže by mohl fungovat vitamín K ???
• pubmed.ncbi.nlm.nih.gov/27210812/

Dendrimer SB105-A10

• Respiratory syncytial virus (RSV) interacts with cell surface heparan sulfate proteoglycans (HSPGs) to initiate infection.
• The interaction of RSV with HSPGs thus presents an attractive target
• Dendrimer SB105-A10 was the most potent inhibitor of RSV infectivity
• 50% inhibitory concentrations (IC(50)s) of 0.35 µM and 0.25 µM measured in Hep-2 and A549 cells, respectively.
• Bind to both cell types via HSPGs
• Competing with RSV for binding to cell surface HSPGs
• Prevented RSV infection when added before the viral inoculum
• Antiviral activity was also exhibited when SB105-A10 was added postinfection
• Reduce the cell-to-cell spread of the virus
• Human-derived tracheal/bronchial epithelial cells cultured to form a pseudostratified, highly differentiated model of the epithelial tissue of the human respiratory tract
• SB105-A10 strongly reduced RSV infectivity in this model and exhibited no signs of cytotoxicity or proinflammatory effects
• SB105-A10 an attractive candidate for further development as a RSV inhibitor to be administered by aerosol delivery.
• pubmed.ncbi.nlm.nih.gov/22850525/

Detralex 2-2-2 + Venoruton + Aescin + Vitamín C

• I když jsem zatím nedohledala přímo toto, že by na RSV bylo, tak mi to opět dává hluboký smysl
• Poškožená tkáň vlivem zánětu a přisedající neutrofily jako problém
• Vede k následnému prosaku až dušení se hleny
• Tomu všemu tyto staré známé netoxické léky, které mohou jíst i těhotné
• ZABRÁNÍ

• 2 až 3 tablety Detralexu v kombinaci s polévkovou lžící Sinupretu v nouzi s čajovou lžičkou Stoptussinu
• Si dávám při atace dráždivého kašle už roky a vždy mne to zachrání do pár minut a dalších x hodin pak mohu mluvit bez dráždivého kašle
• Nemluvě o tom, že mohu i volně dýchat...
• Když jde do tuhého, dávky se opakují a přihodí se další podobné látky "proti otoku"
• Ps.: žíly nemáme jenom v nohách, ale uplně všude - i v plicích

• Další vylepšení starého postupu: Pycnogenol
• Mimo jiné pycngenol prokázal efekt u astmatu, které se často s RS viry spojuje

Dysoxylum gaudichaudianum

• Dysoxylum gaudichaudianum Miq. (Meliaceae)
• Papua New Guinea
• Leaves and bark are used as a medicine (Weiner, 1984)
• Adding boiling water to the chopped leaves is considered to be a cure for most aches and pains (Parham, 1943)
• Anti-RSV agents from Dysoxylum gaudichaudianum were described by Chen et al., 2007.
• Both aqueous (water or 1:1 water-2-propanol) and organic (1:1 methylene chloride-2-propanol) extracts of D. gaudichaudianum bark
• Showed inhibitory activity against the RSV strain A2
• In CPE inhibition and plaque reduction assays

Respiratory syncytial viral CPE inhibition and plaque reduction assays

• 4 new compounds, belonging to the tetranortriterpenoid family
• Dysoxylins A-D,
• Potent anti-viral activity against RSV
• In both the cytopathic effect (CPE) inhibition and plaque reduction assays (1 to 4 ug/ml)

EDP-938

• Works by preventing the virus from making copies of itself in the body
• Can be given as a liquid or a pill.

The study enrolled healthy adults between the ages of 18 and 55

• Who had very low levels of antibodies against the RSV virus
• Experimentally infected with the Memphis 37 strain of the virus
• Placed in a quarantine unit for 12 days, until they tested negativ
• 115 people in the first part of the study and 63 people in the second.
• Took nasal swabs until they detected a brewing infection, then started one of two doses of the medication or a placebo.
• People on the drug were more likely to experience headaches, dizziness and diarrhea compared to those who were taking a placebo.
• At all doses, viral levels were significantly lower in people taking the drug
• Compared to those who got a placebo.
• Those on the drug had fewer symptoms too.
• They made about 70% less mucus than people in the placebo group.
• Because babies have such small airways, they’re the group at highest risk from an RSV infection.
• There’s some evidence that children who get RSV infections may be more likely to develop asthma later in life.
• https://edition.cnn.com/2022/02/17/health/rsv-potential-new-drug/index.html

Echinacea

• Ethanol extract of herb and roots of E. purpurea
• Inhibit the viral induction of various cytokines in a line of human bronchial epithelial cells (BEAS-2B), and in two other human cell lines.
• Rhinoviruses 1A and 14, influenza virus, respiratory syncytial virus, adenovirus types 3 and 11, and herpes simplex virus type 1
• Induced substantial secretion of IL-6 and IL-8 (CXCL8), in addition to several other chemokines, depending on the virus
• In every case however Echinacea inhibited this induction
• Echinacea preparation also showed potent virucidal activity against viruses with membranes,
• Indicating the multi-functional potential of the herb
• pubmed.ncbi.nlm.nih.gov/19409931/

Echinacea purpurea

• Become one of the most popular commercial herbal preparations in North America and Europe
• Numerous reports of immune modulatory properties
• Varied anti-viral properties among different Echinacea species and component parts (Hudson et al., 2005; Vimalanathan et al., 2005)

Echinaforce®

• Ethanol extract of herb and roots of E. purpurea
• Known concentrations of marker compounds
• To inhibit the viral induction of various cytokines in a line of human bronchial epithelial cells (BEAS-2B), and in two other human cell lines
• Echinaforce® to inhibit respiratory syncytial virus (RSV)-induced IL-6 and IL-8 (CXCL8) secretion
• In addition to several other chemokines
• Echinacea inhibited this induction
• Showed substantial virucidal activity against RSV (MIC 2.5µg/ml)
• Indicating the multifunctional potential of the herb
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

Ephedrae Herba

• Through interaction with G glycoprotein
• Phedrae Herba (EH), Cinnamomi Cortex (CC), Armeniacae Semen (AS), and Glycyrrhize Radix (GR)
• Major active compounds are ephedrine, methylephedrine, hippuric acid, and glycyrrhetinic acid
• assets.researchsquare.com/files/rs-262616/v1/f7a67d5d-284b-4ddb-a445-6441988ed293.pdf?c=1646848111

FIP-fve

• An immunomodulatory protein
• Was isolated from Flammulina velutipes

In vivo experiments oral administration of FIP-fve

• Significantly reduce the viral titers of RSV and the level of mRNA in the lungs of mice
• Reduce the secretion of IL-6
• FIP-fve may inhibit RSV replication and RSV-induced inflammation by reducing NF-kappaB translocation
• www.mdpi.com/1420-3049/27/14/4457

• Alleviation of respiratory syncytial virus replication and inflammation
• By fungal immunomodulatory protein FIP-fve from Flammulina velutipes
• Fungal immunomodulatory protein (FIP-fve)
• Isolated and purified from the edible golden needle mushroom (Flammulina velutipes) (Ko et al., 1995).
• 114 amino acid residues
• Stimulate the production of IFN-gamma in PBMCs (Wang et al., 2004).
• Th1 cells produce IFN-gamma
• Essential for the eradication of intracellular pathogens (Teixeira et al., 2005)
• Glial cells are derived from neural progenitor cells with neurotropic JHM strain of mouse hepatitis virus infection
• Treatment of infected cells with IFN-gamma inhibits viral replication in a dose-dependent manner (Whitman et al., 2009)
• Strategies aimed at balancing neonatal Th1 and Th2 responses can facilitate the treatment of allergies (Dubois et al., 2010).
• Study were to assess the ability of FIP-fve to disrupt RSV infection or the following inflammatory responses
• We have shown that FIP-fve suppresses AHR and IL-6 secretion in BALF of RSV-infected BALB/c mice.
• Demonstrated that FIP-fve inhibits plaque formation and IL-6 expression induced by RSV infection.
• FIP-fve down regulates the nuclear translocation of NF-kappa B
• FIP-fve inhibits RSV replication and RSV-induced inflammation via reduction in NF-kappa B translocation.

• www.sciencedirect.com/science/article/abs/pii/S0166354214002435

Fang-Gan mixture stimulation of Interferon gamma

In vitro T plaque formation test

• Antiviral and interferon-inducing effect of Fang-Gan mixture (FGM)
• Direct respiratory syncytia virus (RSV) inactivation effect

Mice

• Protection effect after mice infected by RSV
• FGM could also decrease mice death rate (P less than 0.01) in the experimentation of using parainfluenza virus to attack them
• After 8, 16, 24, 32 hours of injecting FGM into mice abdominal cavity, the authors used CPE method to determine interferon titer of L929 cells
• Highest interferon titer was 98.23 mu/m at the 24th hour
• The interferon induced by FGM was in keeping with the nature of Type I interferon.
• FGM might have strong antiviral effect which is achieved by inducing interferon.
• pubmed.ncbi.nlm.nih.gov/2169355/

Yiqi Fanggan Mixture includes: astragalus flavone, deep-fried atractylodes macrocephala koidz, fortune eupatorium herb, cyrtomium fortunei, white cardamom, windproof, dyers woad root, licorice, jobstears seed

• Intragastric administration once a day for 2 weeks

Flos lonicerae

• CJ 4-16-4 is a promising potent inhibitor of RSV
• Inhibits of RSV in Hep-2 cells maintained in tissue culture at a very low concentration (~0.07 uM)
• With cell toxicity over 400 uM (SI > 5880)
• Cotton rat model of RSV infection
• Drug was able to reduce viral titers
• By ~1 log at dose 12.5 and 25 mg/kg/day
• By >2 log at 100 mg/kg/day
• Antiviral activity was specific as influenza A and B and herpes simplex 1 and 2 viruses were not inhibited (Ojwang et al., 2005).
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

Flammulina velutipes and Ganoderma tsugae

• patents.google.com/patent/TW201306854A/en

Ge-Gen-Tang

• Has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines
• pubmed.ncbi.nlm.nih.gov/22120014/

Fresh ginger (Zingiber officinale)

• Has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines.
• europepmc.org/article/med/23123794
• pubmed.ncbi.nlm.nih.gov/23123794/

Fresh ginger Rhizome

• Better effect when given before viral infection
• Snižuje viral attachment a viral internalization
• HEp-2 cells:
• IC50 was 212.7 µg/mL (2 h before);
• A549 cells:
• IC50 was 26 µg/mL (2 h before)
• IC50 was 82.8 µg/mL (1 h before)
• Secrete IFN-that contributed to the inhibition of viral replication
• www.hindawi.com/journals/ecam/2016/6082729/tab1/

Ginger

• Fresh ginger had the potential to inhibit the attachment and internalisation of the human respiratory syncytial virus (RSV) to both human lung cells and liver cells
• In a dose-dependent manner.
• Treatment with ginger stimulated the mucosal cells to increase sections on
• Interferon-beta (INF-beta) secretions
• Has antiviral effects and thus possibly contributed to the inhibition of the viral infection
• www.ncbi.nlm.nih.gov/pmc/articles/PMC7551890/

Ginseng (naturally dried) Root

• Anti-inflammatory functions:
• Diminishing pulmonary inflammatory response [30]
• Inducing host immune responses toward Th1 type immunity
• IgG2a isotype antibodies +
• IFN-gamma +
• IL-4 -
• CD4 T cell infiltration -
• Cell numbers of CD4+ T (CD3+ CD8-) cells -
• Ratio of CD8+/CD4+ T cells +
• www.hindawi.com/journals/ecam/2016/6082729/tab1/

Panax Korean red ginseng (fermented red) Root

• Improved survival of human lung epithelial cells against RSV infection;
• Inhibited RSV-induced cellular oxidative damage
• Enhanced IFN-gamma production following RSV viral infection
• Blocked induction of RSV-induced proinflammatory gene expression in the human alveolar epithelial cell line
• www.hindawi.com/journals/ecam/2016/6082729/tab1/

• Panax ginseng (Asian red ginseng) steamed root and P. quinquefolius (American ginseng) root

100 Korean adults were randomized - influenza season

• Asian red ginseng extract was provided at a dose of 1 g t.i.d.,
• S standardized to contain 7 mg/g of the sum of ginsenosides Rg1 and Rb1
• Incidence of VRI was significantly lower in the Asian red ginseng group compared to placebo (reduced by about 45%)
• Severity and duration of illness was not significantly different between the groups in those who developed VRI.
• Asian red ginseng was as safe as placebo in this study.

A different extract of Asian ginseng at a dose of 100 mg daily

• To placebo in a double-blind trial in 227 Italian adults
• Influenza immunization after four weeks of supplementation
• Additional treatment period of eight weeks
• Incidence of total VRI was significantly less in the vaccine + ginseng group compared to vaccine + placebo. Influenza antibody titers and natural killer cell activity were significantly higher with Asian ginseng supplementation compared to placebo.
• There were minimal, mild adverse effects.

American ginseng extract standardized to contain

• 80% polysaccharides
• 10% protein from roots of the plant
• Several double-blind clinical trials.

One randomized 279 Canadian adults to either 400 mg of the American ginseng extract

• Or placebo for four months as the influenza season commenced
• Significantly fewer participants in the American ginseng group developed VRI at all than in the placebo group, as well as significantly fewer having more than one VRI.
• Severity and duration of VRI symptoms were significantly lower in the American ginseng group versus placebo.

Group of 198 elderly American adults

• Living in nursing homes and assisted-living facilities, the same American
• Ginseng extract at a dose of 200 mg b.i.d. was compared to placebo
• For 12 weeks.
• Laboratory-confirmed cases of influenza and RSV infection
• Were significantly reduced in the American ginseng group compared to placebo
• no differences in adverse effects.

Same American ginseng extract at the same dose

• In a very similar trial design was confirmed in a study of 43 elderly American adults
• Living in the community who received the influenza vaccination.
• Incidence and duration of VRI was cut in half in the American ginseng group compared to placebo in this trial, a very significant difference in both cases.
• Based on all these studies, Asian and American ginseng look very promising for reducing incidence of VRI during the winter months.

A liquid standardized extract of American ginseng was compared to placebo in a randomized trial of 46 Canadian children (age 3–12 years) with acute VRI

• Dose was weight-based and complicated:
• One group were given 26 mg/kg on day 1, 17 mg/kg on day 2, and 9 mg/kg on day 3 of their VRI
• A second group were given half this dose
• Third group were given placebo
• All doses were divided into three portions throughout the day.
• There was no difference between any of the groups in terms of severity or duration of VRI symptoms
• Was also no difference in adverse effects
• Also suggests that American ginseng is unlikely to be that useful in resolving VRI, and other herbs as discussed above should be favored for this purpose.
• www.liebertpub.com/doi/10.1089/act.2017.29150.eya

Ginseng

• Multiple mechanisms through which ginseng might provide protective efficacy against RSV. RGE inhibited RSV-induced cell death, RSV replication, and the production of pro-inflammatory cytokines in vitro. In addition, RGE treatment in mice upon RSV infection resulted in diminishing mouse body weight loss, lowering lung viral loads, and enhancing antiviral IFN-? production as well as increasing CD8+ T cells and CD11c+ dendritic cells.
• www.ncbi.nlm.nih.gov/pmc/articles/PMC4344572/

Cardiac glycosides

• Inhibitors of the membrane-bound Na+/K+-ATPase
• Identified to have anti-RSV activity
• Diminished RSV infection in human epithelial type 2 cells and in primary human airway epithelial cells grown at an air-liquid interface.
• K+/Na+-sensitive steps in the RSV life cycle

Digoxi

• Was also able to inhibit infection of primary nasal epithelial cells
• With community isolates of RSV
• May be dependent on changes in the intracellular Na+ and K+ composition

Ionophoric antibiotics salinomycin, valinomycin, and monensin

• Inhibited RSV in human epithelial type 2 cells and primary nasal epithelial cells
• pubmed.ncbi.nlm.nih.gov/30095982/

Glycyrrhizae Rhizome Radix

• More effective when given before viral inoculation
• Inhibition of viral attachment and penetration
• In HEp-2 cells:
• IC50 was 78.0 µg/mL (2 h before)
• IC50 was 99.7 µg/mL (1 h before);
• In A549 cells:
• IC50 was 18.8 µg/mL (2 h before)
• IC50 was 33.8 µg/mL (1 h before)
• Stimulate mucosal cells to secrete IFN-beta to counteract viral infection
• www.hindawi.com/journals/ecam/2016/6082729/tab1/

In vitro in Hela cell culture

• Safe and effective anti-RSV new medicine from Radix Glycyrrhizae

was observed by means of the inhibition of cytopathic effect.

• Radix Glycyrrhizae was found to be a inhibitor of RSV in a concentration-dependent manner.
• The median toxic concentration (TC50) of Radix Glycyrrhizae was 3.43 g/L,
• The median effective concentration (EC50) of Radix glycyrrhizae against replication of the Long strain of RSV in Hela cells were 0.2535 g/L
• Selectivity index (TI = TC50/EC50) is 13.53.
• Radix Glycyrrhizae inhibited the effect of RSV in Hela cells when it was added at 0 h, 2 h, 4 h, 6 h, 8 h after virus infection.
• Radix Glycyrrhizae was found to be a inhibitor of RSV, there are many ways in the mechanisms.
• pubmed.ncbi.nlm.nih.gov/15524297/

Čaj z lékořice zalitý vodou 60°C + rozpustit tableta zinku - pak se popíjí

• Bylo popsáno jako efektivní na mnoho jiných viróz

• Anti-respiratory syncytial virus effect of active compound of Glycyrrhiza GD4 in vitro
• pubmed.ncbi.nlm.nih.gov/17059011/

• Water extract of licorice
• Had anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines
• pubmed.ncbi.nlm.nih.gov/23643542/

Heliox

• Směs 21 % O2 a 79 % He, která má nižší viskozitu než vzduch
• Může být prospěšná, ale pro jednoznačný závěr zatím chybějí dostatečné důkazy
• www.ipvz.cz/seznam-souboru/7327-kapitoly-z-detske-pneumologie.pdf

Histone deacetylase inhibitors

• Suppress RSV infection and alleviate virus-induced airway inflammation

Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA)

• RSV infection in airway epithelial cells (AECs) significantly decreased histone acetylation levels by altering HDAC2 expression
• Treatment of RSV-infected AECs with HDACis significantly restricted RSV replication
• By upregulating the interferon-alpha signaling pathways
• Inhibited RSV-induced pro-inflammatory cytokine release  (IL)-6 and IL-8 and oxidative stress
• MDA, NO
• Inhib. activation of NF-kappaB, COX-2, MAPK and Stat3

In vivo study using a mouse model of RSV infection

• HDACis alleviated airway inflammation and reduced in vivo RSV replication
• www.spandidos-publications.com/10.3892/ijmm.2016.2691

Honey

• Antiviral agent against respiratory syncytial virus
• Honey could be used topically
• Pre-treatment of the cells had no effect on the consequent development of cytopathic effect
• Inhibition and neutralisation experiments showed a significant inhibitory effect on the progression of infection
• Suggesting a direct effect on the virus rather than on the cells
• The activity observed did vary
• Some types of honey causing greater inhibition of RSV than others
• There being very little virus detected in honey-treated cells compared with untreated cells infected with RSV
• sugar was not responsible for the inhibition of RSV
• Methylglyoxal may play a part in the greater potency of Manuka honeys against RSV
• researchcommons.waikato.ac.nz/handle/10289/5291

Houttuynia cordata Thunb

• Anti-Respiratory Syncytial Virus Mechanism
• A total of 12 potentially active compounds and 47 potential interaction targets were screened.
• PPI Network and data from GEO showed that IL-6, STAT3, TNF, AKT1, PTGS2, SRC, and MAPK3 may play a core role in the antivirus process.
• KEGG enrichment pathway analysis predicted that H. cordata Thunb exerted its anti-RSV effect by regulating TNF, Rap1, HIF-1, PI3KAkt, MAPK, and VEGF signaling pathways.
• pubmed.ncbi.nlm.nih.gov/32957876/

Hydroclathrus clathratus and Lobophora variegata

• Products from marine organisms
• The water-soluble extracts of seaweeds anti-viral activity against a wide spectrum of viruses
• Crude water extracts of six species of seaweeds
• Hydroclathrus clathratus,
• Lobophora variegata (Lamouroux) Womersley ex Oliveira,
• Showed potent anti-RSV activities with EC50 values of 25 ug/ml and 100µg/ml respectively.
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

L. deflexicalyx

• 3,5-dicaffeoylquinic acid (CJ 4-16-4)
• Potential therapy for RSV infection
• CJ 4-16-4 has a promising antiviral activity against RSV with minimal toxicity.
• www.sciencedirect.com/science/article/abs/pii/S0166354205001956?via%3Dihub

Immunoglobulin with high anti-RSV neutralizing antibody levels (RSVIG)

• For prophylaxis and therapy of RSV infection in cotton rats undergoing prolonged immunosuppression with cyclophosphamide.
• These animals experience persistent infection, a model which is similar to the disease seen in post-BMT humans.
• Both prophylaxis and therapy reduced pulmonary viral replication over 500-fold to nearly undetectable levels.
• In animals receiving continual immunosuppression, the use of multiple therapeutic doses of RSVIG was able to prevent rebound viral replication, though virus was not completely eliminated.
• www.nature.com/articles/1701813

Imunoglobulins

• Current therapies (e.g. inhaled bronchodilators, epinephrine, nebulised hypertonic saline, and corticosteroids)
• Are ineffective or have limited effect.
• Respiratory syncytial virus immunoglobulin
• Sometimes used prophylactically to prevent hospital admission from RSV-related illness
• May be considered for the treatment of established severe RSV infection or for treatment
• Is not licenced for this purpose

Searched the Cochrane Central Register of Controlled Trials (CENTRAL)

• Randomised controlled trials comparing immunoglobulins with placebo in hospitalised infants and children aged up to three years with laboratory-diagnosed RSV lower respiratory tract infection.
• Seven trials involving 486 infants and children aged up to three years
• Anti-RSV immunoglobulin and the monoclonal antibody preparations palivizumab and motavizumab
• Assessed the primary outcomes of mortality, length of hospital stay, and adverse events
• Found no evidence of a difference between immunoglobulins and placebo for mortality
• (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.14 to 5.27; 3 trials; 196 children; 4 deaths; 2 deaths amongst 98 children receiving immunoglobulins, and 2 deaths amongst 98 children receiving placebo.
• Very low-certainty evidence), and length of hospitalisation
• (mean difference -0.70, 95% CI -1.83 to 0.42; 5 trials; 324 children; low-certainty evidence).
• Adverse events of any severity or seriousness (reported in five trials) or serious adverse events (four trials)
• (RR for any severity 1.18, 95% CI 0.78 to 1.78; 340 children; low-certainty evidence, and for serious adverse events 1.08, 95% CI 0.65 to 1.79; 238 children; low-certainty evidence).
• no evidence of a significant difference between immunoglobulins and placebo
• research.bond.edu.au/en/publications/immunoglobulin-treatment-for-hospitalised-infants-and-young-child

Indometacine

• Cyclooxygenases (COXs) are rate-limiting enzymes that initiate the conversion of arachidonic acid to prostanoids.
• COX-2 is the inducible isoform that is up-regulated by proinflammatory agents, initiating many prostanoid-mediated pathological aspects of inflammation.
• The roles of cyclooxygenases and their products, PGs, have not been evaluated during respiratory syncytial virus (RSV) infection.
• In this study we demonstrate that COX-2 is induced by RSV infection of human lung alveolar epithelial cells with the concomitant production of PGs.
• COX-2 induction was dependent on the dose of virus and the time postinfection.
• PG production was inhibited preferentially by NS-398, a COX-2-specific inhibitor, and indomethacin, a pan-COX inhibitor, but not by SC-560, a COX-1-specific inhibitor.

In vivo

• COX-2 mRNA expression and protein production were strongly induced in the lungs and cells derived from bronchioalveolar lavage of cotton rats infected with RSV.
• The pattern of COX-2 expression in vivo in lungs is cyclical, with a final peak on day 5 that correlates with maximal histopathology.
• Treatment of cotton rats with indomethacin significantly mitigated lung histopathology produced by RSV.
• The studies described in this study provide the first evidence that COX-2 is a potential therapeutic target in RSV-induced disease.
• pubmed.ncbi.nlm.nih.gov/15778400/

CAVE: Early indomethacin administration increases oxygen and surfactant requirement.

• academic.oup.com/tropej/article/43/1/42/1718939

Radix Isatidis

• Revealed a multiple-target synergy effect against respiratory syncytial virus
• Through RIG-I and MDA5 signaling pathways
• Radix Isatidis extracts alone or in combination
• Relieved virus-induced mouse lung lesions
• Compared with individual drugs, the lung lesions were alleviated more significantly after treatment with the three fractions in combination
• pubmed.ncbi.nlm.nih.gov/31051218/

Jiawei-Yupingfeng-Tang

• Inhibits respiratory syncitila viral infections in vitro and in vivo

Jinxin oral liquid

• Inhibits human respiratory syncytial virus-induced excessive inflammation associated with blockade of the NLRP3/ASC/Caspase-1 pathway
• Jinxinoral liquid (JOL) is an additive and subtractive formula of Ma Xing Shi Gan Tang (MXSGT).
• MXSGT is a traditional Chinese medicine compound preparation that has been used to treat severe respiratory diseases
• JOL is formed by adding several herbs to MXSGT, including:

• Morus alba L, Lepidium apetalum Willd, Peucedanum praeruptorum Dunn, Scutellariae baicalensis Georgi, and Polygonum cuspidatum Sieb.

• www.sciencedirect.com/science/article/abs/pii/S0753332218310655?via%3Dihub

Lactoferrin

• Heparan sulfate, is a common target for various viruses.
• Several studies have shown that lactoferrin binds to structures containing heparan sulfate, which can prevent viruses from recognizing and entering the cell

LiHeTan contains 13 ingredients

• Liu-He-Tang inhibited plaque formation by human respiratory syncytial virus infection in cell lines of the human respiratory tract
• Extracts of
• Zingiber officinale,
• Chaenomeles sinensis
• Magnolia officinalis
• Possess anti-viral activity against influenza virus,...
• www.sciencedirect.com/science/article/abs/pii/S0378874111005198?via%3Dihub

Ligustrum lucidum (Oleaceae)

• Secoiridoid glucoside compounds, lucidumoside C, oleoside dimethylester, neonuezhenide, oleuropein, ligustroside and lucidumoside A, isolated from the fruits of Ligustrum lucidum

Oleuropein

• Being the most potent (IC50 23.4µg/ml) as well as possessing an overall large and best therapeutic window (TC50 562.5µg/ml/IC50 23.4µg/ml)
• Comparable to that of ribavirin
• Associated immune effects could enhance its anti-RSV benefit in the biological compartment.
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

Lithraea molleoides, Polygonum punctatum and Myrcianthes cisplatensis

• Trees of the genus Lithraea Hook. et Arn. (Anacardiaceae)

Lithraea molleoides (Vell.) - Engler called ‘a ´rbol malo’ (evil tree), common name chichita’, or ‘molle de Co ´rdoba’,

• Produces discomfort, drowsiness, lack of strength, rash and swelling in exposed parts of the body to anyone approaching to the tree.
• Fruits have a volatile oil
• Disturbing irritation of the eyes and the skin (Storni, 1994)
• Fruits are used to make an alcoholic drink
• Infusion of the leaves and fruits - diuretic and stomachic (Cabrera, 1938)
• Tincture and the decoction are a good remedy for cough, bronchitis and phlegm.
• Arthritis (Martius, 1843).
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

Liu-He-Tang

• Inhibited plaque formation by human respiratory syncytial virus infection in cell lines of the human respiratory tract.

• Ethnopharmacol. 2011 Oct 11;137(3):1149-55. doi: 10.1016/j.jep.2011.07.043. Epub 2011 Jul 22. PMID: 21810459

Luteolin

In vitro and in vivo

• Inhibited RSV replication
• Decreased viral titer and RSV-F mRNA expression both
• Enhanced phosphorylation of STAT1,
• Resulting in the increased production of ISGs.
• Further study showed that SOCS1 was downregulated by luteolin and SOCS1 is a direct target of microRNA-155 (miR-155).
• Inhibition of miR-155 rescued luteolin-mediated SOCS1 downregulation, whereas upregulation of miR-155 enhanced the inhibitory effect of luteolin.
• Luteolin inhibits RSV replication by regulating the miR-155/SOCS1/STAT1 signaling pathway.

• pubmed.ncbi.nlm.nih.gov/33239033/ PMID: 33239033 PMCID: PMC7688008 DOI: 10.1186/s12985-020-01451-6
• Luteolin lze koupit v kapslích. Je v cibuli a jablku aj.

Modified dingchuan decoction (MDD)

• Salviae miltiorrhizae radix, Scutellariae radix, Farfarae flos, and Ephedrae herba
• Improve cough, asthma, pneumonia, and bronchiolitis in east China
• In a murine model
• MDD was shown to decrease lung histopathology, viral loads, and inflammatory mediators with low toxicity when given for 3 days.
• In vitro analysis
• Higher selectivity index against RSV than ribavirin in cell lines
• MDD preparations have not been tested outside of murine models in a controlled setting
• www.dovepress.com/respiratory-syncytial-virus-current-and-emerging-treatment-options-peer-reviewed-fulltext-article-CEOR

Mungo sprouts

• Novel antiviral activity of mung bean sprouts against respiratory syncytial virus and herpes simplex virus -1

In vitro study virally infected Vero and MRC-5 cell lines

Myrcianthes cisplatensis (Camb.) Berg. (Myrtaceae) ‘lapachillo’, ‘guayabo colorado’ or ‘palo pelado’

• Infusion of the leaves and the wood decoction
• Astringent, tonic, stimulant, febrifuge and diuretic, and especially useful to wash and heal ulcers (Gonza ´lez Torres, 1992).
• Remedy for lung and bronchial affections (Font Quer, 1988)
• Clear bark and the strong odor of its leaves
• Anti-RSV activities of L. molleoides, P. punctatum and M. cisplatensis extracts
• Reported by Kott et al., 1998
• ED50 values ranging from 78 to 120ug/ml
• Especially against RSV
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

N-acetylcystein

• Protects Airway Epithelial Cells during Respiratory Syncytial Virus Infection
• Against Mucin Synthesis, Oxidative Stress, and Inflammatory Response and Inhibits HSPA6 Expression
• BEAS-2B is an immortalized but nontumorigenic epithelial cell line derived from human bronchial epithelial cells infected by RSV
• NAC protected BEAS-2B cell survival against RSV infection
• RSV-F expression was decreased after NAC administration
• Antiviral activity of NAC has been proved in previous studies.
• Anti-inflammatory property of NAC was confirmed in our study
• TNF-alpha, IL-6, IL-1beta, and IL-18 mRNA expression - NAC group lower
• Reduced/oxidized glutathione (GSH/GSSG) is an indicator of cellular health
• NAC has been demonstrated to reverse the reduction in the GSH/GSSG ratio in the setting of oxidative stress
• Inhibitory effects of NAC on EGFR activation and mucin synthesis in RSV-infected BEAS-2B cells
• Inhibition on mucin hypersecretion caused by RSV infection
• NAC reduce airway inflammation and responsiveness, goblet cell hyperplasia, and lung fibrosis by increasing levels of ROS, nuclear factor erythroid 2-related factor 2, and MUC5AC protein
• NAC treatment reduced mRNA and protein expressions of HSPA6
• Strictly stress-inducible member of Hsp70 family
• www.hindawi.com/journals/acp/2022/4846336/

• N-Acetyl-l-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with Respiratory Syncytial Virus (RSV)
• hal.archives-ouvertes.fr/hal-00721646

Nebulized N-Acetyl Cysteine for Bronchiolitis in Inpatient Hospital Use: A Randomized Controlled Trial, Study Phase 4

• N-Acetyl Cysteine (NAC) is an antioxidant, anti-mucus compound that increases intracellular glutathione at the cellular level.
• Cleaves disulfide bonds by converting them to two sulfhydryl groups.
• Results in the breakup of mucoproteins in lung mucus,
• Reducing their chain lengths and thinning the mucus.
• Nebulized NAC is not studied well in acute bronchiolitis and is uncommonly used for the same.
• Purpose of this study is to evaluate the effectiveness of nebulized mucolytic therapy in treatment of children with viral bronchiolitis.
• www.medifind.com/articles/clinical-trial/5016148

• One cell study evaluated respiratory syncytial virus
• Treatment with N-acetyl-L-cysteine blocks the reproduction of the virus while restoring the normal structure and function of the cells lining the airways

Mata M, Sarrion I, Armengot M, et al. Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human bronchial epithelial cells: effectiveness of N-acetylcysteine. PLoS One. 2012;7(10):e48037.

• www.lifeextension.com/magazine/2020/ss/protect-your-respiratory-system

Mata M, Morcillo E, Gimeno C, et al. N-acetyl-L-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with respiratory syncytial virus (RSV). Biochem Pharmacol. 2011;82(5):548–555

NaCl

• Příznivý efekt inhalace hypertonického 3–7% roztoku Nacl, bez nežádoucích účinků
• www.ipvz.cz/seznam-souboru/7327-kapitoly-z-detske-pneumologie.pdf

Narcissus tazetta

• Bulbs of the Chinese daffodil, Narcissus tazetta var. chinensis
• NTL was obtained, its purity was analysed
• Suggested to be a mannose-binding homodimer with two identical subunits
• NTL could effectively inhibit RSV-induced plaque formation (IC50= 2.30 ug/ml).
• Its cytotoxicity against HEp-2 cells was low (CC50= 325.4 ug/ml)
• Had a high SI value of 141.36.
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

Nemocnice

Possibly effective

Nebulized ipratropium bromide (Atrovent)

• With or without nebulized albuterol (Proventil)*
• Anticholinergic bronchodilator
• no proven efficacy for RSV bronchiolitis
• 321 infants in six research studies
• no significant difference in length of hospital stay between ipratropium bromide and placebo
• no significant difference between the combination of nebulized ipratropium bromide and a beta2-agonist compared with a beta2-agonist alone
• Combined ipratropium bromide and beta2-agonist therapy
• Did show significantly improved clinical scores at 24 hours compared with placebo
• Parents preferred ipratropium bromide over placebo for relief of their children's symptoms at home

Beta2-agonist bronchodilators

• Do not reduce hospital admission rates or meaningfully improve oxygen saturation levels among patients with RSV infections
• Even though short-term clinical scores, in some cases, may improve with treatment
• AHRQ report suggests that larger clinical trials are needed to make sound conclusions.

Oral or inhaled corticosteroids † / Parenteral dexamethasone †

• Remains controversial
• Type of steroid does not seem to make a difference
• no difference in benefit from oral prednisolone or intravenous dexamethasone or budesonide
• Some safety concerns about adverse reactions to budesonide via metered-dose inhaler
• Meta-analysis of corticosteroids for bronchiolitis
• Small, statistically significant improvements in clinical symptoms
• Length of stay, and duration of symptoms
• Subset analysis for first-time wheezing
• Did not reach statistical significance
• Methodologic concerns about clinical trials reporting benefits from corticosteroids administered during the acute phase of viral bronchiolitis
• Omitting any history of atopy or employing retrospective designs
• Allergies or asthma may be confounding conditions accounting for the beneficial actions of corticosteroids among study participants misclassified as having RSV

Nebulized epinephrine ‡

• AHRQ evidence
• Randomized trial published after the AHRQ report was released had sufficient statistical power to demonstrate that nebulized epinephrine therapy does not significantly reduce the length of the hospital stay or the time until infants with bronchiolitis are ready for discharge
• Therapy should be discontinued if there is no significant improvement in clinical assessment within 30 minutes after the first treatment
• www.aafp.org/pubs/afp/issues/2004/0115/p325.html

Possibly effective for most severe cases

Helium-oxygen combination

• One study of short-term helium-oxygen (heliox) combination therapy for acute bronchiolitis, modified asthma scores among 18 infants improved after 20 minutes of therapy.
• This improvement could be the result of reduced airway resistance and decreased breathing work
• Infants with the most severe disease at baseline
• Demonstrated the greatest decrease in severity score
• 30 heliox given via face mask
• Improved clinical scores, reduced tachycardia and tachypnea, and shortened length of stay in the intensive care unit
• Study31 of heliox given to intubated children with bronchiolitis
• Showed there were no benefits in measures of ventilation or oxygenation.

Surfactant

• To improve oxygenation and shorten the duration of ventilatory support and length of stay in the intensive care unit
• Small randomized study demonstrated benefits from administering surfactant in RSV-positive ventilated infants
• Showing a more rapid improvement in oxygenation and ventilation indexes over the first 60 hours of ventilation, which indicates small airway patency and better lung compliance.
• Infants in the placebo group became progressively worse during the first 30 hours after enrollment.
• www.aafp.org/pubs/afp/issues/2004/0115/p325.html

Probably ineffective

Aerosolized ribavirin (Virazole)

• Nucleotide analogue with in vitro activity against influenza A and B, measles, and RSV
• Reduced time on ventilator, shortened length of hospital stay, and improved clinical scores
• Methodologic concerns about some RCTs that studied the use of ribavirin in acute RSV bronchiolitis.
• One study of infants on mechanical ventilation for severe RSV infection, the placebo group received nebulized water, an agent known to cause bronchospasm
• Reported advantage of ribavirin actually may have been caused by adverse effects from the placebo
• Lack of significant differences between the treatment and control groups in a later study
• Meta-analysis concluded there is no evidence to support the use of ribavirin in the treatment of RSV bronchiolitis
• AAP generally does not recommend ribavirin treatment for RSV infections
• AHRQ classifies ribavirin as “probably ineffective.”

Antibiotics (unless patient has a clear focus of bacterial infection)

Nebulized furosemide

RSV-IG (RespiGam)

Inhaled interferon alfa-2a (Roferon-A)

rhDNase

antihistamines, oral decongestants, and nasal vasoconstrictors

• Lack efficacy
• www.aafp.org/pubs/afp/issues/2004/0115/p325.html

Nirsevimab - Beyfortus

• Britain's AstraZeneca and France's Sanofi said on Friday their newly-approved drug nirsevimab
• To prevent severe illness caused by the respiratory syncytial virus (RSV) in infants.
• www.euronews.com/next/2022/11/04/eu-approves-antibody-treatment-to-prevent-rsv-virus-in-babies-as-bronchiolitis-cases-soar

Nirsevimab

• Recombinant human immunoglobulin G1 kappa monoclonal antibody,
• Candidate due to the antibody’s neutralizing activity
• By binding to the highly conserved epitope on the RSV fusion protein.
• Lowered the incidence of respiratory syncytial virus (RSV)-associated lower respiratory tract infection compared to the placebo group.
• www.2minutemedicine.com/prophylactic-nirsevimab-treatment-reduces-rsv-risk-in-infants/

Oregano oil and carvacrol

• Antiviral activity against herpes simplex virus type-1 (HSV-1); rotavirus, a common cause of diarrhea in infants and children; and respiratory syncytial virus (RSV), which causes respiratory infections
• www.healthline.com/nutrition/antiviral-herbs

Paeonia lactiflora pallas

• Anti-viral activity of water extract against human respiratory syncytial virus in human respiratory tract cell lines.

• 2013;41(3):585-99. doi: 10.1142/S0192415X13500419. PMID: 23711143

Intravenous palivizumab and ribavirin combination

• For respiratory syncytial virus disease in high-risk pediatric patients
• Treatment of RSV-infected high-risk children with intravenous palivizumab alone or in combination with ribavirin was well tolerated and associated with decreased mortality compared with previous reports.
• pubmed.ncbi.nlm.nih.gov/18043443/

Palivizumab (Synagis)

• Lidská monoklonální protilátka (IgG1?) proti specifickému epitopu
• Strukturálnímu povrchovému glykoproteinu F (fúzní protein) RSV.
• Neutralizuje virus a inhibuje penetraci virového obalu do plazmatické membrány hostitelské buňky prostřednictvím proteinu F.
• Z lidských (95 %) a z myších (5 %) sekvencí protilátek
• Silný neutralizující a fúzi inhibující účinek proti A i B subtypu RSV.
• Doporučené dávkování palivizumabu je 15 mg/kg tělesné hmotnosti
• Jednou měsíčně v období předpokládaného rizika RSV v komunitě (v ČR listopad – březen)
• Optimální je zahájit aplikaci před začátkem RSV sezóny
• (v ČR poslední týden v říjnu a první týden v listopadu)
• Další dávky jsou podávány v měsíčních intervalech během sezóny
• (konec aplikace poslední týden v únoru nebo první týden v březnu).
• www.pediatriepropraxi.cz/pdfs/ped/2015/04/09.pdf

Palivizumab

• Monoclonal antibody
• Safety and kinetics for treatment of RSV in previously healthy children
• But the study could not detect clinical outcome differences due to small sample size
• Retrospective review found decreased mortality when IV palivizumab (mean dose: 14.9 mg/kg) was used with (80%) or without ribavirin (primarily aerosolized) in 31 children
• Who were immunocompromised (n = 18), premature (n = 5), had congenital heart issues (n = 4), or had other issues (n = 4)
• Twenty-nine patients survived with treatment and no adverse effects were reported.

A phase 1 study found IV palivizumab (15 mg/kg/dose)

• Prevented lower respiratory tract disease in 3 hematopoietic stem cell transplant patients with an RSV upper respiratory tract infection.
• 83% survival rate in 12 transplant patients with RSV interstitial pneumonia for a 28 day study period.
• No adverse effects were reported in this study as well.

• www.ncbi.nlm.nih.gov/pmc/articles/PMC3461981/

Papaverine

• Vasodilator, shows inhibitory action against various strains of influenza virus as well as the paramyxoviruses PIV5, HPIV3, and RSV
• Papaverine as an effective inhibitor of both influenza viruses as well as paramyxoviruses.
• pubmed.ncbi.nlm.nih.gov/31896588/

Pelargonium sidoides - EPs 7630

• Reported to be linked to the production of interferons,9 although a recent study12 highlighted a direct antiviral effect on several viruses (influenza, parainfluenza, respiratory syncytial viruses, rhino viruses, coxsackie, and coronaviruses)

• Numerous clinical trials have widely shown the efficacy of the P. sidoides preparation EPs 7630 in reducing the symptoms resulting from infection of the airways
• From common cold to AB, in the adult population
• The early administration of EPs 7630 has been shown not only to reduce the severity of symptoms
• But also to prepone the start of symptom improvement,
• With a reduction of illness duration
• An earlier resumption of usual activities in the patients affected.

• Trials conducted on pediatric patients that were presented in this review have essentially confirmed the results already observed in the adult population
• With regard to efficacy and safety of use.
• These data allow us to make some considerations that are particularly applicable to the pediatric age: pathologies affecting the airways are the reason for frequent requests for medical assessment and substantial drug prescription; the use of antibiotics for this type of pathology is extremely common, especially when there is a persistent high temperature, even if the etiology is typically viral.
• The early use of EPs 7630 at the onset of signs of respiratory infection
• Reduces or resolves symptoms more rapidly,
• Reduces the risk of bacterial superinfection,
• Allows more rapid functional recovery,
• Reduces the use of other drugs such as
• paracetamol,19 or, most importantly, antibiotics,
• EPs 7630 is well tolerated and can be used in children from the age of 1 year.
• Furthermore, its use could provide preventive action against clinical worsening or complications, while reducing the need for NSAIDs and antibiotics.
• www.ncbi.nlm.nih.gov/pmc/articles/PMC5849386/

• Pelargonium sidoides extract EPs® 7630
• Immunomodulatory and cytoprotective effects
• Inhibition of interaction between bacteria and host cells
• Increase of cilliary beat frequency on respiratory cells
• Antiviral effects may contribute to the beneficial effects exerted by EPs® 7630 in acute bronchitis patients.
• pubmed.ncbi.nlm.nih.gov/21036571/#&gid=article-figures&pid=fig-1-uid-0

Polygonum punctatum Elliot (Polygonaceae)

• Considered poisonous to man and ocasionally fatal to livestock
• Acrid juice can cause both internal and external inflammation
• Astringent, diaphoretic, diuretic and rubefacient properties
• A cold extract can be applied to skin problems, scabies, and hemorrhoids and as a gargle for toothache and problems in the larynx.
• Juice, pure or thinned with water
• Is effective in drawing pus out of sores (Lust, 1974).
• Infusion of the whole plant called ‘erva do bicho’ or ‘caa-tai’, ‘ajicillo’, is used in traditional medicine by the Toba indians of Argentina
• Disinfectant and vulnerary in lavages of pimples, wounds and rash and as an antihemorrhoidal
• (Marti ´nez Crovetto, 1964, 1965, 1981).
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

Prevence přenosu

• Omezení jejich styku s jinými dětmi, především v době sezónního výskytu RSV
• Mytí rukou
• Případně nošení rukavic
• Jsou úhelným kamenem prevence
• RSV se přenáší hlavně kontaminovanými rukama a předměty
• Nošení čistého pracovního oděvu
• Používání obličejových roušek, případně i ochranných brýlí
• V sezóně RSV vyšetřování všech nově přijímaných dětí expresním testem, který detekuje RSV.
• Na povrchu předmětů zůstává RSV infekční nejméně 6 hodin
• Prakticky až 24 hodin na membráně stetoskopu
• Asi 30 minut na kapesníku
• Dbát i na desinfekci stetoskopů !!!
• Vstupní bránou infekce RSV jsou hlavně oční spojivky a sliznice nosu
• Zdravotní personál je v době epidemie RSV-viróz významným přenašečem viru mezi pacienty
• Zvláště když se mimoděk dotýká povrchu svých sliznic, nejen spojivek
• www.khsova.cz/docs/01_odborna_cinnost/files/sms024.pdf

Probiotics Lactobacillus rhamnosus GG, Escherichia coli Nissle 1917 and VSL#3

• Was orally administered to neonatal mice on a daily basis either for 1 week in advance or for 3 days starting from the day of RSV infection.
• Administration of the probiotics protected against RSV-induced lung pathology
• By suppressing RSV infection
• Exerting an antiviral response via alveolar macrophage (AM)-derived IFN-beta
• Administration of the probiotics
• Reversed gut dysbiosis
• Significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria in RSV-infected mice
• Consequently led to elevated serum SCFA levels
• Restored lung microbiota in RSV-infected mice
• Increased production of IFN-beta in AMs
• Was attributed to the
• Increased acetate in circulation
• The levels of Corynebacterium and Lactobacillus in lungs.
• In conclusion, we reveal that probiotics protect against RSV infection in neonatal mice
• Through a microbiota-AM axis
• Probiotics may be a promising candidate to prevent and treat RSV infection, and deserve more research
• www.semanticscholar.org/paper/Probiotics-protect-against-RSV-infection-by-the-Ji-Sun/ae457159f5922723c152c8c50cda58aca53425d5

Ramalina farinaceae

• Some lichens and lichen-derived substances possess anti-viral activities
• (Cohen et al., 1996; Pengsuparp et al., 1995; Neamati et al., 1997)
• Ramalina farinacea, a lichen found to Nigeria, other isolated places
• Anti-retro-viral (including lentiviruses)
• Anti-adenoviral principles (Esimone et al., 2005).
• Antimicrobial (Esimone and Adikwu, 1999; 2002; Esimone et al., 1999; 2006)
• Against the respiratory syncytial virus
• Ethylacetate fraction (ET4) of the plant was effective against RSV (IC50= 3.65µg/ml).
• ET4 targets an entry rather than a post-entry step by inhibiting the RSV fusion protein (Esimone et al.,2009).
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

Ramalina farinaceae

• Some lichens and lichen-derived substances possess anti-viral activities
• (Cohen et al., 1996; Pengsuparp et al., 1995; Neamati et al., 1997)
• Ramalina farinacea, a lichen found to Nigeria, other isolated places
• Anti-retro-viral (including lentiviruses)
• Anti-adenoviral principles (Esimone et al., 2005).
• Antimicrobial (Esimone and Adikwu, 1999; 2002; Esimone et al., 1999; 2006)
• Against the respiratory syncytial virus
• Ethylacetate fraction (ET4) of the plant was effective against RSV (IC50= 3.65µg/ml).
• ET4 targets an entry rather than a post-entry step by inhibiting the RSV fusion protein (Esimone et al.,2009).
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

Resveratrol

• Inhibits respiratory syncytial virus-induced IL-6 production, decreases viral replication, and downregulates TRIF expression in airway epithelial cells
• pubmed.ncbi.nlm.nih.gov/22391746/

• Resveratrol can both affect RSV replication
• Modulate the viral-induced inflammatory response.

Human tracheal epithelial cell line cultures, with human RSV A2-strain

• resveratrol significantly lowered RSV titers at 24-, 48- and 72-hour incubation
• Blocked syncytial formation
• Inhibitory activity was associated with decreased IL-6 production
• Dampening effect on the expression of TIR-domain-containing adapter inducing IFN-b (TRIF) and TANK binding kinase 1 (TBK1) protein
• IL-6 is an essential cytokine that transmits defense signals following a pathogen invasion, but its excessive and sustained production is associated with disease severity
• Uncontrolled response to RSV can be mediated by excessive activation of TLR3, which may contribute to disease worsening

In immunocompromised BALB/c mice infected with human RSV A2-strain

• TLR3 activation stimulated an excessive IFN-g induction that, in this animal model, is associated with severe airway hyperresponsiveness
• In these mice, resveratrol treatment modulated TLR3 expression and significantly reduced the RSV lung titers, the number of infiltrating lymphocytes in bronchoalveolar lavage fluid (BALF), and the recruitment of leukocytes into lung tissues
• Following RSV infection, resveratrol attenuated airway hyperresponsiveness to methacholine, significantly
• Decreasing BALF IFN-g levels
• Promoting the expression of autoinhibitory muscarinic M2 receptors
• M2 muscarinic receptors can inhibit the release of acetylcholine, a neurotransmitter that promotes airway contraction
• resveratrol-induced suppression of persistent airway inflammation and airway hyperresponsiveness was detectable 60 days after RSV infection and was associated with decreased levels of BALF nerve growth factor (NGF)
• Being a neurotrophic factor and inhibiting infected cell apoptosis,
• NGF acts in RSV infection as a promoter of acetylcholine release and as a signaling molecule inducing neuropeptide production and neurogenic inflammation
• noosit.com/wp-content/uploads/2021/08/Resveratrol-and-COVID-19_FRONT-IMMUN.pdf

Inhalační antivirotikum ribavirin (syntetický nukleosid)

• Indikován u imunokompromitovaných dětí při terapii závažných virových pneumonií.
• řadu závažných kontraindikací a nežádoucích účinků.
• www.pediatriepropraxi.cz/pdfs/ped/2015/04/09.pdf

Ribavirin

• Antihepaciviral, nucleoside (Anti-HCV)
• Inhibits replication of RNA and DNA viruses
• Inhibits RNA polymerase activity
• Inhibits the initiation and elongation of RNA fragments which prevents viral protein synthesis.
• www.unmc.edu/intmed/divisions/id/asp/protected-antimicrobials/oral.html

Hospitalizace zdětí při RS viru

Symptomatická ter.

• Supplemental oxygen
• Guided by respiratory rates,
• Work of breathing,
• Oxygen saturation,
• Arterial blood gas values
• Mechanical ventilation
• Fluid replacement
• Bronchodilator therapy with beta agonists
• Unable to tolerate milk or feedings well and frequently vomit or spit up
• Brief course of intravenous (IV) fluids is generally administered in this setting
• Resumption of normal feeding as the child recovers (typically over 2-3 days).

Bronchodilator therapy

• Subset of patients with RSV-related lower respiratory tract infection (LRTI) appear to benefit from
• Alpha agonists (eg, vaporized epinephrine)
• Have also been used during acute bronchiolitis episodes

Ribavirin, a broad-spectrum antiviral agent in vitro

• For the aerosolized treatment of children with severe RSV disease
• Recommended dose is 6 g of drug in 300 mL of distilled water
• Via a small-particle aerosol generator (SPAG unit) over 12-20 hours per day for 3-7 days
• Depending on clinical response
• Equivalent efficacy can be achieved by
• Higher concentration of the drug (6 g/100 mL distilled water)
• Over 3 discrete 2-hour periods per day.
• High acquisition cost and its lack of demonstrated benefit in decreasing hospitalization or mortality
• Primarily reserved for patients with significant underlying risk factors and severe acute RSV disease (eg, transplant recipients).

Immunoglobulins with high anti-RSV antibody titers

• Have proved beneficial when given monthly for prophylaxis in select groups of high-risk infants
• High cost of administering these products (cca $5,000-6,000 per child per year)

RSV immune globulin intravenous (RSV-IGIV)

• Pooled polyclonal human immunoglobulin product
• Prepared from donors with high titers of RSV antibodies
• Administered to high-risk infants with prematurity or chronic lung disease
• Significant decrease in RSV-related hospitalization
• Treated infants have had less severe hospital courses if admitted with RSV disease
• Fewer other respiratory infection hospitalizations,
• Fewer cases of otitis media than placebo recipients.
• RSV-IGIV requires intravenous (IV) administration at a dose of 750 mg/kg monthly
• During RSV season (typically, November through May or April in temperate climates)
• 1998, RSV-IGIV is no longer being manufactured.

Humanized monoclonal anti-RSV antibody palivizumab

• At a dosage of 15 mg/kg/month intramuscularly (IM) per month
• 55% reduction in RSV hospitalization in premature infants born at less than 35 weeks’ gestation
• Who were younger than 6 months chronological age
• In infants who had bronchopulmonary dysplasia and were younger than 24 months chronological age.
• Study in infants younger than 2 years who had hemodynamically significant congenital heart disease
• Also demonstrated safety and efficacy of palivizumab prophylaxis in this high-risk population
• Postmarketing studies continued to demonstrate efficacy
• November 2005, a stable liquid preparation of the drug became available, replacing the lyophilized form used previously
• Dosing and concentration of the liquid preparation have not changed.
• emedicine.medscape.com/article/971488-treatment#d9

Rosmarinus officinalis extract

• Exerted a strong inhibitory effect against hRSV infection

Carnosic acid

• Bioactive constituent responsible for anti-hRSV activity
• Exhibit potent antioxidant and anti-cancer activities
• R. officinalis, carnosic acid displayed the most potent anti-hRSV activity and was effective against both A- and B-type viruses.
• Carnosic acid
• Safe for human consumption
• Has anti-viral activity against hRSV
• Efficiently blocking the replication of this virus
• Carnosic acid inhibited both A- and B- type hRSV
• Did not affect the replication of influenza A virus
• Antiviral activity is hRSV-specific

• Diterpene carnosic acid found to be effective against RNA enveloped respiratory syncytial virus (RSV) with acceptable toxicity
• www.ncbi.nlm.nih.gov/pmc/articles/PMC7129285/

• R. officinalis, carnosic acid displayed the most potent anti-hRSV activity and was effective against both A- and B-type viruses.
• Carnosic acid efficiently suppressed the replication of hRSV
• In a concentration-dependent manner
• Effectively suppressed viral gene expression
• Without inducing type-I interferon production or affecting cell viability
• May directly affect viral factors.
• Addition of carnosic acid 8 hours after infection
• Still effectively blocked the expression of hRSV genes
• Suggesting that carnosic acid directly inhibited the replication of hRSV.
• www.ncbi.nlm.nih.gov/pmc/articles/PMC3852111/

Rutin, schaftoside, and apigenin-6,8-di-C-beta-D-galactoside

• Showed promising top hits docking profile against human respiratory syncytial virus
• Absorption, distribution, metabolism, excretion properties (QikProp) of top hits resulted within an ideal range of kinetic descriptors
• pubmed.ncbi.nlm.nih.gov/29491633/

Sargassum fusiforme and Its Components

• On Replication of Respiratory Syncytial Virus In Vitro and In Vivo
• Medicine and food, is regarded as a marine vegetable and health supplement
• S. fusiforme extract (SFE) has antiviral effects against respiratory syncytial virus (RSV)
• In vitro and in vivo mouse model.
• HEp2 cells with a non-cytotoxic concentration of SFE
• Significantly reduced RSV replication, RSV-induced cell death, RSV gene transcription, RSV protein synthesis, and syncytium formation.
• Oral inoculation of SFE significantly
• Improved RSV clearance from the lungs of BALB/c mice.
• phenolic compounds eicosane, docosane, and tetracosane
• Identified as active components of SFE.
• Treatment with a non-cytotoxic concentration of these three components elicited similar antiviral effects against RSV infection as SFE in vitro.
• Results suggest that SFE and its potential components are a promising natural antiviral agent candidate against RSV infection.
• www.mdpi.com/1999-4915/13/4/548

Schefflera heptaphylla (L.) Frodin

• Principal ingredient of an herbal tea formulation
• Extract of the long leafstalk of the compound leaf of S. heptaphylla exhibited the most potent antiviral activity against respiratory syncytial virus (RSV)
• Active pure triterpenoids
• 3alpha-hydroxylup-20(29)-ene-23,28-dioic acid
• 3-epi-betulinic acid 3-O-sulfate
• pubmed.ncbi.nlm.nih.gov/17357972/

Seaweed Sulfated Polysaccharides

• Against Respiratory Viral Infections
• Natural marine sulfated polysaccharides possessing promising antiviral activity against respiratory viruses
• Could be a safe alternative to synthetic broad-spectrum antiviral drugs.
• pubmed.ncbi.nlm.nih.gov/34065660/

Sinupret(®)

• Herbal medicinal product made from
• Gentian root, Primula flower, Elder flower, Sorrel herb, and Verbena herb
• Antiviral activity of Sinupret(®) oral drops (hereinafter referred to as "oral drops") and Sinupret(®) dry extract (hereinafter referred to as "dry extract")

in vitro against a broad panel of both enveloped and non-enveloped human pathogenic RNA and DNA viruses

• Concentration-dependent antiviral activity (EC(50) between 13.8 and 124.8 ug/ml) of Sinupret(®) was observed against
• RNA as well as DNA viruses
• Independent of a viral envelope
• Remarkable antiviral activity was shown against
• Adeno 5, HRV 14 and RSV
• Dry extract was significantly superior to oral drops
• Results demonstrate that Sinupret(®) shows a broad spectrum of antiviral activity in vitro against viruses commonly known to cause respiratory infections
• pubmed.ncbi.nlm.nih.gov/22112724/

Tanreqing Injection + ganciclovir

• Treatment of respiratory syncytial virus pneumonia in children
• Search
• pubmed.ncbi.nlm.nih.gov/32957408/

TCM herbs

• 41 showed anti-RSV activities
• 25 herbs showing the strongest potency (IC50= 6.3 to 52.1ug/ml)
• Largest selective index (SI= 4.0 to 32.1):

Andrographis paniculata,

Artemisia capillaries,

Bupleurum chinense,

Callicarpa nudiflora,

Dendranthema morifolium,

Forsythia suspensa,

Ipomoea cairica,

Gardenia jasminoides,

Isatis indigotica,

Lonicera japonica,

Paeonia suffruticosa,

Patrinia _illosa,

Perilla frutescens,

Phragmites communis,

Platycodon grandiflorum,

Polygonum cuspidatum,

Polygonum multiflorum,

Prunella vulgaris,

Pueraria lobata,

Sarcandra glabra,

Schizonepeta tenuifolia,

Scutellaria baicalensis,

Selaginella sinensis,

Sophora flaescens

Tinospora capillipes

• All of these traditional Chinese medicines extracts were considered active

Sophora flaescens Ait. w and Scutellaria baicalensis Georgi

• Aqueous extracts from
• Purification of 2 of the herbs Sophora flavescens and Scutellaria baicalensis
• Led to the isolation of potent anti-viral compounds
• Sophora flaescens and of Scutellaria baicalensis were further investigated

• anagyrine, oxymatrine, sophoranol, wogonin, and oroxylin A

• As the most potent anti-viral compounds against RSV
• IC50 values ranged from 7.4 to 14.5 ug/ml.
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf

Theofyllin

• Může snížit výskyt obstrukční apnoe, proto při potížích s dýcháním se doporučuje jej zkusit
• www.khsova.cz/docs/01_odborna_cinnost/files/sms024.pdf

Triazole-1

• As an RSV replication inhibitor
• Inhibited the replication of both RSV A and B subtypes with IC 50 values of approximately 1 µM but
• Was not effective against other viruses
• Inhibit RSV replication when added at up to 8 hrs after viral entry
• Suggesting it inhibits RSV after the viral entry.
• Triazole-1 demonstrated specific and dose-dependent RSV transcription inhibitory effects.
• www.researchgate.net/publication/350509873_Discovery_of_a_Novel_Respiratory_Syncytial_Virus_Replication_Inhibitor

Respiratory syncytial virus (RSV) vaccine - ADE reaction !!

• RSV is a virus that commonly causes pneumonia in children
• A vaccine was made by growing RSV,
• Purifying it, and inactivating it with the chemical formaldehyde.
• In clinical trials, children who were given the vaccine
• Were more likely to develop or die from pneumonia after infection with RSV !!!!
• Vaccine trials stopped
• Vaccine was never submitted for approval or released to the public.
• www.chop.edu/centers-programs/vaccine-education-center/vaccine-safety/antibody-dependent-enhancement-and-vaccines

Cathelicidins / 1,25(OH) metabolite of vitamin D + butyrate

• Immunomodulatory cationic host defense peptides
• Key component of innate immunity
• Expressed in neutrophils and epithelial cells, and airway epithelial cell expression
• Induced in vitro by RSV infection
• Significantly upregulated by the 1,25(OH) metabolite of vitamin D

Human cathelicidin LL-37

• Significant dose-related reduction in infectivity
• Direct effect on the viral particles
• Reduced susceptibility of the bronchial epithelial cells to infection
• RSV-infected human epithelial cells to LL-37
• Resulted in significant reduction in cell apoptosis compared to untreated cells
• Postexposure treatment with LL-37
• Showed that spread of the virus in human epithelial cells can be limited and thereby protect the intact epithelium
• Antiviral activity of LL-37 is retained by a truncated peptide fragment, which opens the possibility of development of shorter peptide analogs
• Enhancing LL-37 expression with drugs such as

Butyrate

Vitamin D

4-Phenylbutyrate

• Shown to upregulate h-CAP-18/LL-37 expression in human airway epithelial cells in vitro,
• Especially when acute short-term upregulation is required

A meta-analysis literature on vitamin D receptor polymorphisms

• Association between the Fokl vitamin D receptor polymorphism and RSV severity
• Studies of cord blood vitamin D levels
• Birth 25-hydroxy vitamin D concentrations pod 50 nmol/L increase the risk of RSV in the first year of life by sixfold

Vitamin D intervention studies

• Pediatric randomized trial in Mongolia
• Ability of vitamin D to reduce acute respiratory events
• Specific reduction in RSV incidence has not been delineated to date
• www.dovepress.com/respiratory-syncytial-virus-current-and-emerging-treatment-options-peer-reviewed-fulltext-article-CEOR

Watsonianone A from Rhodomyrtus tomentosa Fruit

• Attenuates Respiratory-Syncytial-Virus-Induced Inflammation In Vitro
• Inhibitory effect on RSV-induced NO production
• Half-maximal inhibitory concentration of 37.2 ± 1.6 uM
• Watsonianone A
• Markedly reduced both mRNA and protein levels of
• Tumor necrosis factor alpha,
• Interleukin 6,
• Monocyte chemoattractant protein 1 in RSV-infected RAW264.7 cells
• www.researchgate.net/publication/316444868_Watsonianone_A_from_Rhodomyrtus_tomentosa_Fruit_Attenuates_Respiratory-Syncytial-Virus-Induced_Inflammation_In_Vitro

4'-methoxydaphnodorin E from Wikstroemia indica

• Against respiratory syncytial virus (RSV)
• In vitro anti-RSV activity with cytopathic effect (CPE) reduction assay
• Potent effect with 50% inhibitory concentration (IC50) value of 2.8 uM
• Selective index (SI) value of 5.4.
• www.tandfonline.com/doi/abs/10.1080/10286020.2011.653963?journalCode=ganp20

Xiao-Qing-Long-Tang (XQLT, TJ-19, Sho-seiryu-to, so-cheong-ryong-tang)

• Hot water extract of XQLT dose-dependently inhibited HRSV-induced plaque formation in both HEp-2 and A549 cells (P<0.0001)
• Particularly when given before viral inoculation (p<0.0001).
• XQLT inhibited viral attachment (p<0.0001) and internalization (p<0.0001).
• 300µg/ml XQLT could decrease both the number and the size of HRSV-induced syncytium without clear effect on the production of viral F protein.
• XQLT could stimulate epithelial cells to secrete IFN-ß before and after viral inoculation to counteract viral infection (p<0.0001).
• XQLT is effective against HRSV infection on airway epithelia by preventing viral attachment, internalization, syncytial formation, and by stimulating interferon secretion.
• www.sciencedirect.com/science/article/abs/pii/S0378874113002006?via%3Dihub

Xiao-Qing-Long-Tang (Sho-seiryu-to)

• Inhibited cytopathic effect of human respiratory syncytial virus in cell lines of human respiratory tract.

• Chang JS, Yeh CF, Wang KC, Shieh DE, Yen MH, Chiang LC. J Ethnopharmacol. 2013 May 20;147(2):481-7. doi: 10.1016/j.jep.2013.03.044. Epub 2013 Mar 27. PMID: 23542148

Youngia japonica

• Anti-RSV activity of the ethanol extract
• Biannual medicinal herb, Youngia japonica (commonly known as Oriental hawk’s beard)
• Two potent anti-RSV compounds
• 3,4-dicaffeoylquinic acid
• 3,5-dicaffeoylquinic acid
• From the ethanol extract of Youngia japonica
• Exhibited prominent anti-RSV with an IC50 of 0.5ug/ml
• no sign of cytotoxicity up to 100ug/ml concentration.
• cdn.intechopen.com/pdfs/24398/InTech-Anti_respiratory_syncytial_virus_agents_from_phytomedicine.pdf