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First-generation oral antivirals against SARS-CoV-2
Parham Sendi1, Raymund R Razonable2, Sandra B Nelson3
1Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
Summary
First-generation oral antivirals for COVID-19 offer treatment options but require careful use. Molnupiravir and nirmatrelvir/ritonavir have shown efficacy, yet present challenges like drug interactions and toxicity concerns.
Area of Science:
- Pharmacology
- Infectious Diseases
- Drug Development
Background:
- Oral antiviral agents for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization for treating mild-to-moderate COVID-19 in high-risk, non-hospitalized patients.
- Molnupiravir and nirmatrelvir/ritonavir are authorized, with clinical trials indicating risk reduction for hospitalization or death.
Purpose of the Study:
- To provide a clinical practice overview of first-generation oral antiviral agents targeting SARS-CoV-2.
- To highlight key considerations for the clinical use of these novel therapeutics.
Main Methods:
- Literature review including searches of PubMed, Google Scholar, bioRxiv, medRxiv, and regulatory/pharmaceutical websites.
- Data compilation and analysis of clinical trial results and drug authorizations up to February 16, 2022.
Main Results:
- Molnupiravir demonstrated a 30% relative risk reduction in hospitalization/death; nirmatrelvir/ritonavir showed an 89% reduction.
- Clinical use necessitates early administration, careful review of drug-drug interactions (nirmatrelvir/ritonavir), and consideration of embryo-fetal toxicity (molnupiravir).
- Knowledge gaps exist regarding efficacy in vaccinated, hospitalized, or immunosuppressed populations with persistent SARS-CoV-2.
Conclusions:
- First-generation oral antivirals represent therapeutic progress against SARS-CoV-2 but introduce new clinical challenges.
- Further development of novel oral antiviral drugs is essential to address ongoing therapeutic needs.
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