A phase 2–3, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of simnotrelvir plus ritonavir in treating mild-to-moderate Covid-19 in adults. The study enrolled 1208 patients in China, with 603 assigned to simnotrelvir and 605 to placebo. The primary endpoint was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Simnotrelvir significantly reduced this time compared to placebo (180.1 hours vs. 216.0 hours; P=0.006). The simnotrelvir group also showed greater viral load reduction by day 5 (-1.51 log10 copies/mL vs. -1.24 log10 copies/mL). Adverse events were more common in the simnotrelvir group (29.0% vs. 21.6%), but most were mild or moderate. The drug showed no evident safety concerns. Simnotrelvir was effective in shortening symptom resolution time and reducing viral load, with the most significant antiviral effect observed on day 5. The study highlights the potential of simnotrelvir as a treatment option for mild-to-moderate Covid-19. The trial was funded by Jiangsu Simcere Pharmaceutical and registered at ClinicalTrials.gov (NCT05506176).A phase 2–3, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of simnotrelvir plus ritonavir in treating mild-to-moderate Covid-19 in adults. The study enrolled 1208 patients in China, with 603 assigned to simnotrelvir and 605 to placebo. The primary endpoint was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Simnotrelvir significantly reduced this time compared to placebo (180.1 hours vs. 216.0 hours; P=0.006). The simnotrelvir group also showed greater viral load reduction by day 5 (-1.51 log10 copies/mL vs. -1.24 log10 copies/mL). Adverse events were more common in the simnotrelvir group (29.0% vs. 21.6%), but most were mild or moderate. The drug showed no evident safety concerns. Simnotrelvir was effective in shortening symptom resolution time and reducing viral load, with the most significant antiviral effect observed on day 5. The study highlights the potential of simnotrelvir as a treatment option for mild-to-moderate Covid-19. The trial was funded by Jiangsu Simcere Pharmaceutical and registered at ClinicalTrials.gov (NCT05506176).