publication . Preprint . 2020

Predicted success of prophylactic antiviral therapy to block or delay SARS-CoV-2 infection depends on the drug's mechanism of action

Peter Czuppon; Florence Débarre; Antonio Gonçalves; Olivier Tenaillon; Alan S. Perelson; Jeremie Guedj; François Blanquart;
Open Access English
  • Published: 12 Nov 2020
  • Publisher: HAL CCSD
  • Country: France
Abstract
Abstract Repurposed drugs that are immediately available and have a good safety profile constitute a first line of defense against new viral infections. Despite a limited antiviral activity against SARS-CoV-2, several drugs serve as candidates for application, not only in infected individuals but also as prophylaxis to prevent infection establishment. Here we use a stochastic model to describe the early phase of a viral infection. We find that the critical efficacy needed to block viral establishment is typically above 80%. This value can be improved by combination therapy. Below the critical efficacy, establishment can still sometimes be prevented; for that purpose, drugs blocking viral entry into target cells (or equivalently enhancing viral clearance) are more effective than drugs reducing viral production or enhancing infected cell death. When a viral infection cannot be prevented because of high exposure or low drug efficacy, antivirals can still delay the time to reach detectable viral loads from 4 days when untreated to up to 30 days. This delay flattens the within-host viral dynamic curve, and possibly reduces transmission and symptom severity. These results suggest that antiviral prophylaxis, even with reduced efficacy, could be efficiently used to prevent or alleviate infection in people at high risk. It could thus be an important component of the strategy to combat the SARS-CoV-2 pandemic in the months or years to come.
Persistent Identifiers
Subjects
Medical Subject Headings: viruses
free text keywords: [SDV]Life Sciences [q-bio], Viral load, Transmission (medicine), Mechanism (biology), Combination therapy, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Efficacy, Antiviral therapy, Immunology, Medicine, business.industry, business, Viral entry
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  • COVID-19
Funded by
EC| PolyPath
Project
PolyPath
Insights from within-host dynamics on the coexistence of antibiotic resistant and sensitive pathogens
  • Funder: European Commission (EC)
  • Project Code: 844369
  • Funding stream: H2020 | MSCA-IF-EF-ST
,
ANR| TheraCoV
Project
TheraCoV
Viral dynamics at the individual and population levels: impact for antiviral treatment optimization
  • Funder: French National Research Agency (ANR) (ANR)
  • Project Code: ANR-20-COVI-0018
,
ANR| TheoGeneDrive
Project
TheoGeneDrive
Theoretical Exploration of the Feasibility, Challenges and Risks of Synthetic Gene Drives
  • Funder: French National Research Agency (ANR) (ANR)
  • Project Code: ANR-19-CE45-0009
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