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Drug Development


In preclinical tests, Merck’s COVID-19 antiviral seems to work against variants

Molnupiravir, now in Phase 3 testing, causes SARS-CoV-2 to make major mistakes while copying its genetic code

by Megha Satyanarayana
September 29, 2021 | A version of this story appeared in Volume 99, Issue 36


A photo of two capsules of molnupiravir.
Credit: Merck & Co.
Merck & Co. reports that its oral antiviral molnupiravir is effective against SARS-CoV-2 variants in preclinical tests. SARS-CoV-2 is the virus that causes COVID-19.

Merck & Co. is reporting preclinical work showing that the experimental COVID-19 treatment it is developing with Ridgeback Biotherapeutics will likely block common variants of the SARS-CoV-2 virus, including the highly transmissible Delta variant.

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The treatment, an oral antiviral called molnupiravir, is in two Phase 3 human clinical trials, one as a treatment for early COVID-19 disease, the other for prevention of SARS-CoV-2 infection.

The experiments on variants were not performed in humans, but Jay Grobler, Merck’s executive director of infectious diseases and vaccines, says that “molnupiravir is equally active across all the variants we looked at,” and that the variants the firm tested are representative of those circulating the globe. Because of when the experiments were performed, the data do not include the newly described Mu variant.

The results were reported during IDWeek, the annual meeting of several infectious disease organizations, including the Infectious Diseases Society of America. If molnupiravir is cleared by the US Food and Drug Administration, it will be only the second approved COVID-19 antiviral. Gilead Sciences’ Veklury (remdesivir) has been in use for much of the 18-month pandemic, but the treatment is an infusion that must be given in the hospital.

Molnupiravir is a nucleoside analog—it looks like the natural building blocks of the virus’s genome, so when the SARS-CoV-2 virus tries to copy itself, the enzyme that stitches that genetic information together is fooled into incorporating the antiviral into the growing chain. The virus can’t easily build itself with that doctored information, and it becomes non-infectious.

“Even if you see the virus, it can’t replicate,” Grobler says. “It’s sort of like a dead-end product.”

The molnupiravir tests were very preliminary: the compound was only examined for its ability to prevent the growth of virus in cells. But Grobler says he is confident the results will be similar in people with COVID-19. To that end, Merck and Ridgeback are collecting virus samples from people in the ongoing Phase 3 trials to determine which variant each person has. Those trials are expected to be completed in the coming months.


This story was updated on Sept. 29, 2021, to correct the name of Merck & Co.'s partner. It is Ridgeback Biotherapeutics, not Ridgeback Therapeutics. It was updated on Oct. 1, 2021, to correct the trade name of remdesivir. It is Veklury, not Velkury.



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