Nudix hydrolase 18 catalyzes the hydrolysis of active triphosphate metabolites of the antivirals remdesivir, ribavirin, and molnupiravir.

ABSTRACT: Remdesivir and molnupiravir have gained considerable interest because of their demonstrated activity against SARS-CoV-2. These antivirals are converted intracellularly to their active triphosphate forms remdesivir-TP and molnupiravir-TP. Cellular hydrolysis of these active metabolites would consequently decrease the efficiency of these drugs; however, whether endogenous enzymes that can catalyze this hydrolysis exist is unknown. Here, we tested remdesivir-TP as a substrate against a panel of human hydrolases and found that only Nudix hydrolase (NUDT) 18 catalyzed the hydrolysis of remdesivir-TP with notable activity. The k_cat/K_m value of NUDT18 for remdesivir-TP was determined to be 17,700 s^-1M^-1, suggesting that NUDT18-catalyzed hydrolysis of re

SUBMITTER: Jemth AS 

PROVIDER: S-EPMC9212496 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature