Molnupiravir is being developed for the treatment of COVID, which has been submitted for review by the US Food and Drug Administration, but large-scale production to treat COVID is still a challenge. Now, researchers have engineered enzymes to help manufacture the pill, resulting in a much shorter synthesis with a higher yield than current methods. The details of their work are reported in ACS Central Science.
The oral antiviral molnupiravir was originally developed to treat influenza, and 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 hospitalisation and death from COVID for newly diagnosed, at-risk patients, and that it had equal effectiveness against different SARS-CoV-2 variants. Researchers set out to develop a shorter, higher-yielding and sustainable way to synthesise the molecule.
The team came up with a three-step synthesis of molnupiravir from ribose, a sugar molecule. 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 catalysed 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.
Source: American Chemical Society
