LAUSR

There is an urgent need for an effective, oral, direct-acting therapeutic to block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent progression to severe coronavirus disease 2019 (COVID-19). In a phase 2a double-blind, placebo-controlled, randomized, multicenter clinical trial, we evaluated the safety, tolerability, and antiviral efficacy of the nucleoside analog molnupiravir in 202 unvaccinated participants with confirmed SARS-CoV-2 infection and symptom duration <7 days. Participants were randomized 1:1 to receive molnupiravir (200 mg) or placebo and then 3:1 to receive molnupiravir (400 or 800 mg) or placebo, orally twice daily for 5 days. Antiviral activity was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 RNA in nasopharyngeal swabs. Infectious virus was assessed by inoculation of cultured Vero cells with samples from nasopharyngeal swabs and was detected by RT-PCR. Time to viral RNA clearance (primary endpoint) was decreased in the 800-mg molnupiravir group (median 14 days) compared to the placebo group (median 15 days) (log rank P value = 0.013). Of participants receiving 800 mg of molnupiravir, 92.5% achieved viral RNA clearance compared with 80.3% of placebo recipients by study end (4 weeks). Infectious virus (secondary endpoint) was detected in swabs from 1.9% of the 800-mg molnupiravir group compared with 16.7% of the placebo group at day 3 of treatment (P = 0.016). At day 5 of treatment, infectious virus was not isolated from any participants receiving 400 or 800 mg of molnupiravir compared with 11.1% of placebo recipients (P = 0.034 and 0.027, respectively). Molnupiravir was well tolerated across all doses. Description Molnupiravir (800-mg dose) accelerated SARS-CoV-2 RNA clearance in patients with COVID-19 compared to placebo. An oral drug to fight SARS-CoV-2 Despite the availability of safe and effective vaccines, SARS-CoV-2 continues to spread globally, contributing to high morbidity and mortality. Current treatments are logistically challenging to provide on a global scale, increasing the need for safe and effective oral therapies. In a randomized, controlled, double-blind, multidose study of the drug molnupiravir in adult outpatients with COVID-19, an 800-mg dose reduced viral RNA more rapidly than placebo and eliminated infectious virus in nasopharyngeal swabs (Fischer et al.). Molnupiravir was safe and well tolerated. The rapid elimination of infectious virus has important implications for the prevention of SARS-CoV-2 transmission.