First-generation oral antivirals against SARS-CoV-2

Parham Sendi, Raymund R. Razonable, Sandra B. Nelson, Alex Soriano, Rajesh Tim Gandhi

Research output: Contribution to journalReview articlepeer-review


Background: Oral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization for the treatment of mild-to-moderate COVID-19 in non-hospitalized patients who are at high risk for clinical progression. Objectives: To provide a clinical practice overview of first-generation oral antiviral agents against SARS-CoV-2. Sources: References for this review were identified through searches of PubMed, Google Scholar, bioRxiv, medRxiv, regulatory drug agencies, and pharmaceutical companies' websites up to 16 February 2022. Content: Molnupiravir and nirmatrelvir and ritonavir have been authorized for use in nonhospitalized individuals with mild-to-moderate COVID-19 who are at high risk for progression. In clinical trials, molnupiravir reduced the frequency of hospitalization or death by 3% (relative risk reduction 30%), and nirmatrelvir and ritonavir by 6% (relative risk reduction 89%). Their use in clinical practice requires early administration, review of drug-drug interactions (nirmatrelvir and ritonavir), considerations of embryo-fetal toxicity (molnupiravir), and compliance with ingestion of a high number of pills. Knowledge gaps include the efficacy of these agents in vaccinated, hospitalized, or immunosuppressed individuals with prolonged SARS-CoV-2 persistence. Implications: First-generation oral antivirals represent progress in therapeutics against SARS-CoV-2, but also pose new challenges in clinical practice. Further advances in the development of new drugs are required.

Original languageEnglish (US)
Pages (from-to)1230-1235
Number of pages6
JournalClinical Microbiology and Infection
Issue number9
StatePublished - Sep 2022


  • COVID-19
  • Coronavirus
  • Molnupiravir
  • Nirmatrelvir
  • SARS-CoV-2

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases


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