Highly-transmissible Variants of SARS-CoV-2 May Be More Susceptible to Drug Therapy Than Wild Type Strains
Schöning et al.,
Highly-transmissible Variants of SARS-CoV-2 May Be More Susceptible to Drug Therapy Than Wild Type Strains,
Research Square, doi:10.21203/rs.3.rs-379291/v1 (Preprint)
In Silico study of ivermectin treatment predicting greater efficacy for variants with higher R0.
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.
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.
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Schöning, Sars2variants (2021)
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Highly-transmissible variants of SARS-CoV-2 may be more
susceptible to drug therapy than wild type strains
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Authors: Verena Schöning 1 , Charlotte Kern1,2 , Carlos Chaccour 3,4,5 , Felix Hammann1*
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Clinical Pharmacology and Toxicology, Department of General Internal Medicine,
Inselspital, Bern University Hospital, University of Bern, Switzerland
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Graduate School for Health Sciences, University of Bern, Switzerland
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ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
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Clínica Universidad de Navarra, Pamplona, Spain
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Ifakara Health Institute, Ifakara, United Republic of Tanzania
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Corresponding author:
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Felix Hammann
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Department of General Internal Medicine
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University Hospital Bern
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Freiburgstr. 18
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3031 Switzerland
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Tel.: +41 31 632 5464
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Felix.Hammann@insel.ch
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Keywords: COVID-19, mutations, variant of concern, antiviral, repurposing
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Counts: Abstract: 200 w, body: 1340 w, ref: 17, figs: 2, tables: 0
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Schöning, Sars2variants (2021)
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Abstract
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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).
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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).
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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.
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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.
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Schöning, Sars2variants (2021)
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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