Abstract: Highly-transmissible Variants of SARS-CoV-2 May Be More Susceptible to Drug Therapy Than Wild Type Strains Verena Schöning University of Bern Charlotte Kern University of Bern Carlos Chaccour ISGlobal, Hospital Clínic - Universitat de Barcelona Felix Hammann (  Felix.Hammann@insel.ch ) University of Bern Research Article Keywords: COVID-19, mutations, variant of concern, antiviral, repurposing DOI: https://doi.org/10.21203/rs.3.rs-379291/v1 License:   This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Schöning, Sars2variants (2021) 2 Highly-transmissible variants of SARS-CoV-2 may be more susceptible to drug therapy than wild type strains 3 Authors: Verena Schöning 1 , Charlotte Kern1,2 , Carlos Chaccour 3,4,5 , Felix Hammann1* 4 5 6 7 8 9 1 1 Clinical Pharmacology and Toxicology, Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland 2 Graduate School for Health Sciences, University of Bern, Switzerland 3 ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain 4 Clínica Universidad de Navarra, Pamplona, Spain 5 Ifakara Health Institute, Ifakara, United Republic of Tanzania 10 11 Corresponding author: 12 Felix Hammann 13 Department of General Internal Medicine 14 University Hospital Bern 15 Freiburgstr. 18 16 3031 Switzerland 17 Tel.: +41 31 632 5464 18 Felix.Hammann@insel.ch 19 20 Keywords: COVID-19, mutations, variant of concern, antiviral, repurposing 21 Counts: Abstract: 200 w, body: 1340 w, ref: 17, figs: 2, tables: 0 22 1 Schöning, Sars2variants (2021) 23 Abstract 24 25 26 27 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). 28 29 30 31 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). 32 33 34 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. 35 36 37 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. 38 2 Schöning, Sars2variants (2021)