Antiviral Accelerates Resolution of Mild COVID-19 Symptoms


Early administration of simnotrelvir plus ritonavir shortened the time to sustained resolution of COVID-19 symptoms.

Photo credit: ACS Pharmacol. Transl. Sci. 2023, 6, 9, 1306-1309

Photo credit: ACS Pharmacol. Transl. Sci. 2023, 6, 9, 1306-1309

An antiviral approved in China accelerated the resolution of symptoms among patients with mild-to-moderate COVID-19 by approximately 1.5 days for patients treated within 3 days after symptom onset. Early administration of simnotrelvir plus ritonavir (Xiannuoxin) was found to be officious without evident safety concerns, according to a new study published in the New England Journal of Medicine.

Developed by Simcere Pharmaceutical and conditionally approved by China by the National Medical Products Administration, simnotrelvir plus ritonavir is a pharmaceutical therapy used for the treatment of COVID-19. Simnotrelvir plus ritonavir is a combination therapy of simnotrelvir, an inhibitor of SARS-CoV-2 3CLpro, and ritonavir, a CYP3A inhibitor.1

In the study, a total of 1208 patients were included across 35 sites in China, with 603 designated to receive simnotrelvir plus ritonavir and 605 assigned to receive a placebo. The duration was 180.1 hours, 95% confidence interval (CI), 162.1 to 201.6 for the simnotrelvir group, and 216.0 hours, 95% CI, 203.4 to 228.1 for the placebo group. They had a median difference of −35.8 hours (95% CI, −60.1 to −12.4) and a probability value of 0.006 according to the Peto–Prentice test.

In the phase, 2/3 trials targeting mild-to-moderate COVID-19, the combination of simnotrelvir and ritonavir led to a reduction in the time to sustained symptom resolution and demonstrated greater benefits in alleviating respiratory symptoms compared to the placebo. Additionally, there was an observed additional decline in viral load with simnotrelvir plus ritonavir until day 9, with the most significant antiviral effect observed on day 5.

By day 5, the reduction in viral load from baseline was more pronounced in the therapy group compared to the placebo group, with a mean difference (±SE) of −1.51±0.14 log10 copies per milliliter and a 95% CI of −1.79 to −1.24. The occurrence of adverse events during treatment was elevated in the simnotrelvir group in comparison to the placebo group (29.0% vs. 21.6%). It's noteworthy that the majority of reported adverse events were of mild or moderate severity.

3 Key Takeaways

  1. A new alternative, simnotrelvir plus ritonavir, is tested for the treatment of mild-to-moderate COVID-19, aiming to expedite the resolution of symptoms in patients with SARS-CoV-2 infections.
  2. Early administration of simnotrelvir plus ritonavir resulted in a significantly shorter time to sustained resolution of COVID-19 symptoms among adult patients.
  3. The phase 2/3 trial demonstrated that the combination of simnotrelvir and ritonavir not only reduced the time to sustained symptom resolution by approximately 1.5 days but also exhibited greater benefits in alleviating respiratory symptoms compared to the placebo.

There were some limitations in the trial investigators reported. “First, we recruited vaccinated people, approximately half of whom had risk factors for severe COVID-19. The trial population is similar to the general population in terms of immunity against SARS-CoV-2 and risk-factor status. Second, although the double-blind design of the trial decreases the placebo effect in symptom evaluation, the placebo contained only excipients; therefore, unblinding may have occurred in some patients, given the unique taste of ritonavir,” investigators wrote. “Third, the recruited population was relatively young. The efficacy and safety among older patients still warrant investigations in future research. Finally, both nasopharyngeal and oropharyngeal swabs were used in this trial. However, the sampling method was consistent in nearly all patients (excluding four) across the trial visits.2

The duration for the resolution of systemic symptoms and fever was comparable between the two groups. Analyzing the daily score for each of the 11 COVID-19 symptoms and signs revealed that the resolution of cough, stuffy or runny nose, and sore or dry throat played a pivotal role in alleviating COVID-19 symptoms. Moreover, on the first day of treatment, the simnotrelvir group exhibited a significantly greater reduction in fever, headache, chill, stuffy nose, shortness of breath, muscle aches, and body aches compared to the placebo group.

All in all, when simnotrelvir plus ritonavir was administered early to adult patients with COVID-19, it was successful in reducing the time it took for the symptoms of the disease to resolve. The treatment showed effectiveness and there were no apparent safety issues associated with the early administration of this combination treatment.


  1. Zhu K. Deuremidevir and simnotrelvir-ritonavir for the treatment of COVID-19. ACS Pharmacology & Translational Science. 2023;6(9):1306-1309.
  2. Cao B, Wang Y, Lu H, et al. Oral simnotrelvir for adult patients with mild-to-moderate COVID-19. N Engl J Med. 2024;390(3):230-241. doi:10.1056/NEJMoa2301425
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