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In the first ever direct comparison between the two leading COVID antivirals molnupiravir and nirmatrelvir (Paxlovid®), researchers report in this week’s Lancet Infectious Diseases that while both drugs worked, nirmatrelvir (Paxlovid®) was more effective, clearing the virus from the throat more rapidly than molnupiravir.

Researchers doing a COVID test

28 Sept 2023, Bangkok – After recruiting 209 patients in the Faculty of Tropical Medicine, Mahidol University, Thailand, the researchers found that although the estimated mean rate of SARS-CoV-2 viral clearance with molnupiravir was 37% faster than no study drug, viral clearance was 84% faster with ritonavir-boosted nirmatrelvir.

“Nirmatrelvir (Paxlovid®) is clearly the most active antiviral drug tested to date in the PLATCOV platform trial, but it has some disadvantages: its companion ritonavir is associated with drug interactions and, like others, we documented rebounds of COVID after stopping the five-day course,” said study co-Principal Investigator (PI) Prof Sir Nick White, based at the Mahidol Oxford Tropical Medicine Research Unit (MORU), in Bangkok.

Noting that there have been no direct comparisons before between these and other antiviral COVID medicines – despite the billions of dollars spent on them – the Mahidol-based University of Oxford affiliated researchers developed a simple method of quickly assessing the antiviral activity of COVID drugs in people with mild infections based on frequent measurements of the amount of virus at the back of the mouth.

In 2021, they started PLATCOV – a series of studies to compare all the antiviral drugs that were being used to treat COVID-19 infections.

“It is surprising that with so much attention and concern over COVID-19, and so much money spent, that direct head to head comparisons between medicines have not been conducted to inform public healthcare spending and guidelines,” said Dr William Schilling, first author, study co-PI and a University of Oxford DPhil student based at MORU in Bangkok.

This testing method sets the stage for future rapid comparisons of antiviral drugs for COVID.

“The PLATCOV platform is a simple, well tolerated method of comparing antiviral drugs in patients with mild infections. It provides critical information on antiviral activity. COVID-19 is still common – and large clinical trials are expensive and take time. We cannot be sure that COVID will not become serious again, so we need methods of comparing medicines rapidly to inform treatment guidelines,” said Dr Podjanee Jittamala, joint first author of the paper and Research Physician in MORU’s Clinical Therapeutic Unit (CTU).


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The Mahidol Oxford Tropical Medicine Research Unit (MORU),, @MORUBKK, is a research collaboration between Mahidol University (Thailand), the University of Oxford and Wellcome (UK). 

PLATCOV is an ongoing, open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform trial running in Thailand, Brazil, Pakistan, and Laos PDR. Sponsored by the University of Oxford, funded by the Wellcome Trust ACT-Accelerator, and led by co-PIs Prof Sir Nick White and Dr Will Schilling, of MORU, PLATCOV is a collaboration between the Faculty of Tropical Medicine, Mahidol University, and the MORU Tropical Health Network (MORU).


Antiviral efficacy of molnupiravir versus ritonavir-boosted nirmatrelvir in patients with early symptomatic COVID-19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial. Schilling WHK, Jittamala P et al., on behalf of the PLATCOV Collaborative Group. Lancet ID. Published online 28 Sept 2023