Abstract
The Covid-19 pandemic highlights the urgent need for cost-effective processes to rapidly manufacture antiviral drugs at scale. Here we report a concise biocatalytic process for Molnupiravir, a nucleoside analogue recently approved as an orally available treatment for SARS-CoV-2. Key to the success of this process was the development of an efficient biocatalyst for the production of N -hydroxy-cytidine through evolutionary adaption of the hydrolytic enzyme cytidine deaminase. This engineered biocatalyst performs >85 000 turnovers in less than 3 h, operates at 180 g/L substrate loading, and benefits from in situ crystallization of the N -hydroxy-cytidine product (85% yield), which can be converted to Molnupiravir by a selective 5′-acylation using Novozym 435.
【초록키워드】 Treatment, SARS-CoV-2, pandemic, molnupiravir, COVID-19 pandemic, antiviral drugs, antiviral drug, Cytidine deaminase, cytidine, enzyme, nucleoside, selective, benefit, highlight, approved, less, 【제목키워드】 Production, intermediate, Deaminase,