Dec. 5 Preclinical Quick Takes: Simpler synthesis of Merck’s HIV therapy; plus MRSA antibiotic, once-monthly oral contraceptive

Merck, Codexis design efficient synthesis of Phase II HIV therapy
Merck & Co. Inc. (NYSE:MRK) and Codexis Inc. (NASDAQ:CDXS) researchers designed a way to synthesize HIV therapy islatravir (MK-8591) via a three-step biocatalytic cascade in a single aqueous solution using nine enzymes -- five engineered using Codexis’ CodeEvolver platform. The overall yield using the new process, described in a Science report, was 51%, and Codexis CEO John Nicols told BioCentury the process confers increases in capital efficiencies. The authors had written that previously published synthesis methods require 12-18 steps. Codexis is supplying Merck with enzymes to produce islatravir for late-phase clinical trials. Merck has the nucleoside analog in Phase II testing and announced plans for Phase III testing in July.

Canadian team IDs antibiotic for MRSA
A Canadian team has discovered a glycopeptide-resistance-associated protein R (GraR) inhibitor that resensitized methicillin-resistant Staphylococcus aureus (MRSA) to methicillin and raised sensitivity to cefuroxime, another β-lactam antibiotic. According to a Nature Chemical Biology article, the benzoyl thiourea-based compound as monotherapy blocked biofilm formation in S. aureus culture, inhibited bacterial replication inside cultured macrophages, and raised the survival rate of infected moth larvae...