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All Studies   Meta Analysis    Recent:   

Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies

Swargiary, A., Research Square, doi:10.21203/rs.3.rs-73308/v1
Sep 2020  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now with p < 0.00000000001 from 104 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19ivm.org
In Silico study showing high binding affinity of ivermectin with SARS-CoV-2 RNA-dependent RNA polymerase, suggesting ivermectin as an inhibitor of RdRp.
68 preclinical studies support the efficacy of ivermectin for COVID-19:
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N766, Dengue32,67,68, HIV-168, Simian virus 4069, Zika32,70,71, West Nile71, Yellow Fever72,73, Japanese encephalitis72, Chikungunya73, Semliki Forest virus73, Human papillomavirus52, Epstein-Barr52, BK Polyomavirus74, and Sindbis virus73.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins66,68,69,75, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing33, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination36,76, shows dose-dependent inhibition of wildtype and omicron variants31, exhibits dose-dependent inhibition of lung injury56,61, may inhibit SARS-CoV-2 via IMPase inhibition32, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation5, inhibits SARS-CoV-2 3CLpro49, may inhibit SARS-CoV-2 RdRp activity24, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages55, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation77, may inhibit SARS-CoV-2 by disrupting CD147 interaction78-81, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1954,82, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage4, may minimize SARS-CoV-2 induced cardiac damage35,43, increases Bifidobacteria which play a key role in the immune system83, has immunomodulatory46 and anti-inflammatory65,84 properties, and has an extensive and very positive safety profile85.
Swargiary et al., 9 Sep 2020, preprint, 1 author.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies
Ananta Swargiary
doi:10.21203/rs.3.rs-73308/v1
Purpose: COVID-19, caused by SARS-CoV2 virus is a contagious disease affecting millions of lives throughout the globe. Currently, there are no clinically approved drugs for SARS-CoV2 although some drugs are undergoing clinical trials. The present study investigates the binding property of ivermectin on four important drug targets, spike protein, RNA-dependent RNA polymerase, 3-chymotrypsin-and papainlike proteases of SARS-CoV2. Methods: The 3D structure of ivermectin along with known antiviral drug lopinavir, simeprevir and four nucleotides ATP, GTP, CTP, and UTP were
Ethics approval: NA Consent to participate: NA Consent for publication: Author gives the consent to publish the manuscript
References
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Benvenuto, Giovanetti, Ciccozzi, Spoto, Angeletti et al., The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res, doi:10.1002/jmv.25688
Canga, Prieto, Liebana, Martinez, Vega et al., The Pharmacokinetics and Interactions of Ivermectin in Humans -A Mini-review, AAPS J, doi:10.1208/s12248-007-9000-9
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Patrì, Fabbrocini, Hydroxychloroquine and ivermectin: A synergistic combination for COVID-19 chemoprophylaxis and treatment?, J Am Acad Dermatol, doi:10.1016/j.jaad.2020.04.017
Sharun, Dhama, Patel, Pathak, Tiwari et al., Ivermectin, a new candidate therapeutic against SARS-CoV-2/COVID-19, Ann Clin Microbiol Antimicrob, doi:10.1186/s12941-020-00368-w
Touret, Gilles, Barral, Nougairede, Helden et al., In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication, Sci Rep, doi:10.1038/s41598-020-70143-6
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