When administered at a human effect size-equivalent dose, the oral drug molnupiravir efficiently blocked the transmission of SARS-CoV-2 transmission in ferrets, a new study shows.

The study also finds that two oral drugs, molnupiravir and paxlovid (nirmatrelvir/ritonavir), provide equivalent therapeutic benefit in preventing severe COVID-19 in animal models.

The study published in the journal Nature Communications compared the efficacy of the two licensed drugs, and the effects on SARS-CoV-2 transmission in dwarf hamster and ferret animal models. The researchers established correlations for animal and human dose levels, which can be complex.

Both drugs have received emergency use authorization, but therapeutic options against SARS-CoV-2 are underutilized. Effective treatments against SARS-CoV-2 are critical because extensive viral spread continues, despite the development of vaccines and antivirals.

Also, the rise of new SARS-CoV-2 variants of concern that can escape preexisting immunity have reduced the possibility of rapidly ending the pandemic through large-scale vaccination campaigns.

“This study affirms previous clinical analyses that early treatment of older adult patients at elevated risk of progression to severe COVID-19 with either paxlovid or molnupiravir will provide significant therapeutic benefit,” says Richard Plemper, professor and director of the Center for Translational Antiviral Research at Georgia State University’s Institute for Biomedical Sciences.

“We demonstrate in two animal model species, one rodent and one non-rodent, that infectious particle titers, but not viral RNA copy numbers, should be assessed to determine efficacy of a viral mutagen such as molnupiravir.

“Using reduction of viral RNA copies as biomarker available across all animal models and human patients, we demonstrate that molnupiravir, but not paxlovid, prevents all SARS-CoV-2 transmission when drugs were administered at human effect size-equivalent doses.”

The researchers compared both drugs in two animal models, the Roborovski dwarf hamster model for severe COVID-19-like lung infection and the ferret SARS-CoV-2 transmission model.

“Recent data has indicated another uptick in COVID-19 infections in a broad cross-section of the population. Antiviral drugs can play an important role in not only treating COVID-19 infection but also in controlling its transmission and spread,” says George Painter, professor of pharmacology and chemical biology at Emory University School of Medicine and director of the Emory Institute for Drug Development which developed molnupiravir.

“This collaborative study shows that molnupiravir treatment completely suppresses transmission at all dose levels tested. We look forward to continued studies to verify these exciting results.”

Additional coauthors are from the University of Washington, Emory University, and Georgia State.

The National Institute of Allergy and Infectious Diseases of the National Institutes of Health funded the work.

Source: Georgia State University

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