1. Engineered Ribosyl-1-Kinase Enables Concise Synthesis of Molnupiravir, an Antiviral for COVID-19.
- Author
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McIntosh JA, Benkovics T, Silverman SM, Huffman MA, Kong J, Maligres PE, Itoh T, Yang H, Verma D, Pan W, Ho HI, Vroom J, Knight AM, Hurtak JA, Klapars A, Fryszkowska A, Morris WJ, Strotman NA, Murphy GS, Maloney KM, and Fier PS
- Abstract
Molnupiravir (MK-4482) is an investigational antiviral agent that is under development for the treatment of COVID-19. Given the potential high demand and urgency for this compound, it was critical to develop a short and sustainable synthesis from simple raw materials that would minimize the time needed to manufacture and supply molnupiravir. The route reported here is enabled through the invention of a novel biocatalytic cascade featuring an engineered ribosyl-1-kinase and uridine phosphorylase. These engineered enzymes were deployed with a pyruvate-oxidase-enabled phosphate recycling strategy. Compared to the initial route, this synthesis of molnupiravir is 70% shorter and approximately 7-fold higher yielding. Looking forward, the biocatalytic approach to molnupiravir outlined here is anticipated to have broad applications for streamlining the synthesis of nucleosides in general., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)
- Published
- 2021
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