publication . Article . 2021

Success of prophylactic antiviral therapy for SARS-CoV-2: predicted critical efficacies and impact of different drug-specific mechanisms of action

Peter Czuppon; Florence Débarre; Antonio Gonçalves; Olivier Tenaillon; Alan S. Perelson; Jeremie Guedj; François Blanquart;
Open Access English
  • Published: 01 Mar 2021
  • Publisher: HAL CCSD
  • Country: France
Abstract
Repurposed drugs that are safe and immediately available constitute a first line of defense against new viral infections. Despite limited antiviral activity against SARS-CoV-2, several drugs are being tested as medication or as prophylaxis to prevent infection. Using a stochastic model of early phase infection, we evaluate the success of prophylactic treatment with different drug types to prevent viral infection. We find that there exists a critical efficacy that a treatment must reach in order to block viral establishment. Treatment by a combination of drugs reduces the critical efficacy, most effectively by the combination of a drug blocking viral entry into cells and a drug increasing viral clearance. Below the critical efficacy, the risk of infection can nonetheless be reduced. Drugs blocking viral entry into cells or enhancing viral clearance reduce the risk of infection more than drugs that reduce viral production in infected cells. The larger the initial inoculum of infectious virus, the less likely is prevention of an infection. In our model, we find that as long as the viral inoculum is smaller than 10 infectious virus particles, viral infection can be prevented almost certainly with drugs of 90% efficacy (or more). Even when a viral infection cannot be prevented, antivirals delay the time to detectable viral loads. The largest delay of viral infection is achieved by drugs reducing viral production in infected cells. A delay of virus infection flattens the within-host viral dynamic curve, possibly reducing transmission and symptom severity. Thus, antiviral prophylaxis, even with reduced efficacy, could be efficiently used to prevent or alleviate infection in people at high risk.
Author summary Antiviral therapy taken prophylactically can prevent a viral infection. Administering antiviral drugs in prophylaxis to health care workers or other people at risk could be especially important in the SARS-CoV-2 pandemic. Monoclonal antibodies against the SARS-CoV-2 spike protein and small molecule antiviral drugs could be used for pre- or post-exposure prophylaxis. We predict that combination therapy with two drugs with different modes of action and enough efficacy have the potential to fully prevent SARS-CoV-2 infection. We provide a prediction for the critical combination of drug efficacies above which viral establishment is suppressed entirely. Prophylactic antiviral therapy could be feasible, efficient, and alleviate the burden on healthcare systems.
Persistent Identifiers
Fields of Science and Technology classification (FOS)
03 medical and health sciences, 0301 basic medicine, 0302 clinical medicine, 030212 general & internal medicine, 030304 developmental biology
Sustainable Development Goals (SDG)
3. Good health
Subjects
Medical Subject Headings: viruses
free text keywords: [SDV]Life Sciences [q-bio], [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Research Article, Biology and Life Sciences, Immunology, Vaccination and Immunization, Antiviral Therapy, Medicine and Health Sciences, Public and Occupational Health, Preventive Medicine, Microbiology, Virology, Viral Transmission and Infection, Viral Load, Organisms, Viruses, RNA viruses, Coronaviruses, SARS coronavirus, SARS CoV 2, Medical microbiology, Microbial pathogens, Viral pathogens, Pathology and laboratory medicine, Pathogens, Pharmacology, Drugs, Antimicrobials, Antivirals, Microbial Control, Viral Structure, Virions, Prophylaxis, Pharmaceutics, Drug Therapy, Computational Theory and Mathematics, Cellular and Molecular Neuroscience, Genetics, Molecular Biology, Ecology, Modeling and Simulation, Ecology, Evolution, Behavior and Systematics, Biology (General), QH301-705.5, Viral load, Viral entry, Transmission (medicine), Virus, Medicine, business.industry, business, Virology, Drug repositioning, Risk of infection, Drug, media_common.quotation_subject, media_common, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Communities
Communities with gateway
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Other Communities
  • 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
Validated by funder
,
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
,
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
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