FOR IMMEDIATE RELEASE

ACS News Service Weekly PressPac: November 03, 2021

A quick, high-yield synthesis of molnupiravir, an investigational COVID antiviral pill

"Engineered Ribosyl-1-Kinase Enables Concise Synthesis of Molnupiravir, an Antiviral for COVID-19"
ACS Central Science

As SARS-CoV-2 continues to spread and mutate, it’s important to identify new treatment options. Molnupiravir is an investigational oral antiviral being developed for the treatment of COVID-19, and has been submitted for review by the U.S. Food and Drug Administration. Researchers now report in ACS Central Science that they have engineered enzymes to help manufacture the pill, resulting in a much shorter and higher-yielding synthesis than current methods.

Originally developed to treat influenza, molnupiravir works by causing viruses to make errors when copying their own RNA, introducing mutations that inhibit replication. Recently, interim phase 3 clinical trial findings indicated that molnupiravir reduced the risk of hospitalization and death from COVID-19 for newly diagnosed, at-risk patients, and that it worked equally well against different SARS-CoV-2 variants. John McIntosh, Patrick Fier and colleagues at Merck and Codexis set out to develop a shorter, higher-yielding and sustainable way to synthesize the molecule.

The researchers developed a three-step synthesis of molnupiravir from a sugar molecule called ribose. They identified enzymes or chemical treatments to sequentially add the appropriate chemical groups to ribose to generate the molecule. For the second step of the synthesis, the team identified bacterial enzymes that weakly catalyzed the desired reactions. Using in vitro evolution, they greatly enhanced these enzymes’ activities. The new synthetic route, which also included a phosphate recycling strategy, was 70% shorter and had a seven-fold higher overall yield than the original route.

The authors acknowledge funding from Merck Sharp & Dohme Corp.

 

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.

To automatically receive press releases from the American Chemical Society, contact newsroom@acs.org.

###

Note: ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies.

A new synthetic route could help ensure an adequate supply of molnupiravir, a promising antiviral drug for COVID-19.
A new synthetic route could help ensure an adequate supply of molnupiravir, a promising antiviral drug for COVID-19.
Credit: Copyright © 2009-2021 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A. All rights reserved.
View larger image