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Highly-transmissible Variants of SARS-CoV-2 May Be More Susceptible to Drug Therapy Than Wild Type Strains

Schöning et al., Research Square, doi:10.21203/rs.3.rs-379291/v1
Apr 2021  
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In Silico study of ivermectin treatment predicting greater efficacy for variants with higher R0.
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Yang, West Nile Yang, Yellow Fever Mastrangelo, Varghese, Japanese encephalitis Mastrangelo, Chikungunya Varghese, Semliki Forest virus Varghese, Human papillomavirus Li, Epstein-Barr Li, BK Polyomavirus Bennett, and Sindbis virus Varghese.
Ivermectin is an inhibitor of importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), a SARS-CoV-2 3CLpro inhibitor Mody, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model of severe infection/inflammation that shares key pathological features of severe COVID-19 DiNicolantonio, Zhang, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage Zhao, may minimize SARS-CoV-2 induced cardiac damage Liu, Liu (B), has immunomodulatory Munson and anti-inflammatory DiNicolantonio (B), Yan properties, and has an extensive and very positive safety profile Descotes.
Schöning et al., 15 Apr 2021, preprint, 4 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
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Highly-transmissible Variants of SARS-CoV-2 May Be More Susceptible to Drug Therapy Than Wild Type Strains
Verena Schöning, Charlotte Kern, Carlos Chaccour, Felix Hammann
doi:10.21203/rs.3.rs-379291/v1
As of March 2021, no antiviral drug regimen has proved effective against SARS-CoV-2 infection. With the pandemic showing no signs of slowing down, and vaccine campaigns only starting to be rolled out, we appear to have few options other than non-pharmacological measures. Emerging Variants of Concern (VOCs), e.g. B1.1.7, B.1.351, and B.1.1.248, however, are characterized by higher transmissibility (R0). Here we model and simulate the effect of altered R0 on viral load profiles, and its impact on antiviral therapy. As a hypothetical case study, we simulated treatment with ivermectin 600µg/kg for 3 days initiated at different time points around the infection. Simulated mutations range from 1.25 to 2-fold greater infectivity, but also include putative co-adapted variants with lower transmissibility (0.75-fold). Antiviral efficacy was correlated with R0, making highly transmissible VOCs more sensitive to antiviral therapy. Viral exposure was reduced by 42% compared to 22% in wild type if treatment was started on inoculation. Less transmissible variants appear less susceptible. Our findings suggest there may be a role for pre-or post-exposure prophylactic antiviral treatment in areas with presence of highly transmissible variants. Furthermore, clinical trials with borderline efficacious results should consider identifying VOCs and examine their impact in post-hoc analysis.
Author contributions VS: formal analysis, investigation, methodology, software, visualisation, writing -review & editing; CK: methodology, software, writing -review & editing; CC: validation, funding acquisition, writing -review & editing; FH: conceptualisation, formal analysis, funding acquisition, methodology, software, supervision, validation, visualisation, writing -original draft, writing -review & editing. All authors contributed to the final version. Additional Information Competing interests The author(s) declare no competing interests. above the serological positivity threshold (b). Black: wild type, blue: less transmissible, orange to red: highly transmissible. Supplementary Files This is a list of supplementary les associated with this preprint. Click to download. 20210330Sars2variantssupplements.pdf
References
Baric, Emergence of a Highly Fit SARS-CoV-2 Variant, N Engl J Med, doi:10.1056/NEJMcibr2032888
Canini, Perelson, Viral kinetic modeling: state of the art, Journal of pharmacokinetics and pharmacodynamics, doi:10.1007/s10928-014-9363-3
Chaccour, Hammann, Ramon-Garcia, Rabinovich, Ivermectin and COVID-19: Keeping Rigor in Times of Urgency, Am J Trop Med Hyg, doi:10.4269/ajtmh.20-0271
Chaccour, The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebocontrolled, randomized clinical trial, EClinicalMedicine, doi:10.1016/j.eclinm.2020.100720
Cohen, South Africa suspends use of AstraZeneca's COVID-19 vaccine after it fails to clearly stop virus variant, Science
Duthaler, Population pharmacokinetics of oral ivermectin in venous plasma and dried blood spots in healthy volunteers, Br J Clin Pharmacol, doi:10.1111/bcp.13840
Fajnzylber, SARS-CoV-2 viral load is associated with increased disease severity and mortality, Nat Commun, doi:10.1038/s41467-020-19057-5
Faria, Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings
Goncalves, Timing of Antiviral Treatment Initiation is Critical to Reduce SARS-CoV-2 Viral Load, CPT Pharmacometrics Syst Pharmacol, doi:10.1002/psp4.12543
He, Temporal dynamics in viral shedding and transmissibility of COVID-19, Nat Med, doi:10.1038/s41591-020-0869-5
Kern, Schoening, Chaccour, Hammann, Modeling of SARS-CoV-2 treatment effects for informed drug repurposing, Front Pharmacol
Kim, Modelling SARS-CoV-2 Dynamics: Implications for Therapy, medRxiv, doi:10.1101/2020.03.23.20040493
Rambaut, Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations
Schmith, Zhou, Lohmer, The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19, Clin Pharmacol Ther, doi:10.1002/cpt.1889
Siemieniuk, Drug treatments for covid-19: living systematic review and network meta-analysis, Bmj, doi:10.1136/bmj.m2980
Tegally, Emergence and rapid spread of a new severe acute respiratory syndromerelated coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa, medrXiv, doi:10.1101/2020.12.21.20248640
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Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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