Effectiveness of Antiviral Therapy in Highly-Transmissible Variants of SARS-CoV-2: A Modeling and Simulation Study.

Schöning, Verena; Kern, Charlotte; Chaccour, Carlos; Hammann, Felix (2022). Effectiveness of Antiviral Therapy in Highly-Transmissible Variants of SARS-CoV-2: A Modeling and Simulation Study. Frontiers in Pharmacology, 13, p. 816429. Frontiers 10.3389/fphar.2022.816429

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As of October 2021, neither established agents (e.g., hydroxychloroquine) nor experimental drugs have lived up to their initial promise as antiviral treatment against SARS-CoV-2 infection. While vaccines are being globally deployed, variants of concern (VOCs) are emerging with the potential for vaccine escape. VOCs are characterized by a higher within-host transmissibility, and this may alter their susceptibility to antiviral treatment. Here we describe a model to understand the effect of changes in within-host reproduction number R0, as proxy for transmissibility, of VOCs on the effectiveness of antiviral therapy with molnupiravir through modeling and simulation. Molnupiravir (EIDD-2801 or MK 4482) is an orally bioavailable antiviral drug inhibiting viral replication through lethal mutagenesis, ultimately leading to viral extinction. We simulated 800 mg molnupiravir treatment every 12 h for 5 days, with treatment initiated at different time points before and after infection. Modeled viral mutations range from 1.25 to 2-fold greater transmissibility than wild type, 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. Total viral load was reduced by up to 70% in highly transmissible variants compared to 30% in wild type if treatment was started in the first 1-3 days post 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 SARS-CoV-2 variants. Furthermore, clinical trials with borderline efficacious results should consider identifying VOCs and examine their impact in post-hoc analysis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine

Graduate School:

Graduate School for Health Sciences (GHS)

UniBE Contributor:

Schöning, Verena; Kern, Charlotte and Hammann, Felix

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1663-9812

Publisher:

Frontiers

Language:

English

Submitter:

Pubmed Import

Date Deposited:

01 Mar 2022 09:51

Last Modified:

06 Mar 2022 01:54

Publisher DOI:

10.3389/fphar.2022.816429

PubMed ID:

35222030

Uncontrolled Keywords:

COVID–19 SARS–CoV-2 variants mathematical disease modeling molnupiravir paxlovid pharmacometrics variants of concern (VOCs) viral kinetic modelling

BORIS DOI:

10.48350/166218

URI:

https://boris.unibe.ch/id/eprint/166218

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