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The oral antiviral ensitrelvir is a highly effective treatment for COVID-19, showing potent in-vivo antiviral activity comparable to ritonavir-boosted nirmatrelvir (Paxlovid), say MORU, Mahidol and University of Oxford researchers in a major international study published in The Lancet Infectious Diseases.

Individual patient estimated virus clearance half-lives grouped by treatment group. Courtesy of The Lancet Infectious Diseases.
Individual patient estimated virus clearance half-lives grouped by treatment group. Courtesy of The Lancet Infectious Diseases.

The MORU-led phase 2 PLATCOV trial enrolled 604 adults with early symptomatic COVID-19 in Thailand and Laos. Researchers report in The Lancet Infectious Disease  that ensitrelvir accelerated SARS-CoV-2 viral clearance by 82% compared with no treatment, only slightly slower than Paxlovid. Both drugs were well tolerated, with far fewer patients reporting dysgeusia (bitter or metallic taste) with ensitrelvir.

The findings confirm that ensitrelvir, which requires only once-daily dosing and no ritonavir boosting, is an effective and well-tolerated alternative oral antiviral for COVID-19.

“Ensitrelvir offers an alternative promising, affordable, and simpler option for treating COVID-19. Although the disease is now much less severe, many could still benefit from treatment. Unfortunately there are few options, and those currently available have significant drawbacks,” said lead researcher University of Oxford Prof Sir Nicholas White, co-Head of the Medical Therapeutics Unit (MTU), MORU, in Bangkok.

The study was funded by the Wellcome Trust COVID-19 Therapeutics Accelerator and coordinated by MORU’s Medical Therapeutics Unit (MTU). Jointly overseen by Prof Sasithon Pukrittayakamee and Prof Sir Nick White, MTU conducts the world’s largest chemoprevention and pharmacometric (PK-PD) studies of COVID-19 (COPCOV, PLATCOV) and influenza (AD ASTRA). These innovative PK-PD studies provide a methodology for the rapid assessment, evaluation and monitoring of antiviral interventions in respiratory infection epidemics and pandemics. This was a conspicuous and costly gap during the COVID-19 pandemic.

- Text: Will Schilling. Image: The Lancet Infectious Diseases.

 

Antiviral efficacy of oral ensitrelvir versus oral ritonavir-boosted nirmatrelvir in COVID-19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial. Schilling WHK, Jittamala P, Wongnak P, Watson JA, Boyd S, Luvira V, Siripoon T, Ngamprasertchai T, Batty EM, Beer E, Singh S, Asawasriworanan T, Seers T, Phommasone K, Evans TJ, Kruabkontho V, Ngernseng T, Tubprasert J, Abdad MY, Madmanee W, Kouhathong J, Suwannasin K, Pagornrat W, Piteekan T, Hanboonkunupakarn B, Poovorawan K, Potaporn M, Srisubat A, Loharjun B, Chotivanich K, Imwong M, Pukrittayakamee S, Dondorp AM, Day NPJ, Piyaphanee W, Phumratanaprapin W, White NJ; PLATCOV Collaborative Group. Lancet Infect Dis. 2025 Oct 10:S1473-3099(25)00482-7. doi: 10.1016/S1473-3099(25)00482-7. Epub ahead of print. PMID: 41082886.