The Mac1 ADP-ribosylhydrolase is a therapeutic target for SARS-CoV-2.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a threat to public health. Current therapeutics remain limited to direct-acting antivirals that lack distinct mechanisms of action and are already showing signs of viral resistance. The virus encodes an ADP-ribosylhydrolase macrodomain (Mac1) that plays an important role in the coronaviral life cycle by suppressing host innate immune responses. Genetic inactivation of Mac1 abrogates viral replication in vivo by potentiating host innate immune responses. However, it is unknown whether this can be achieved by pharmacologic inhibition and can therefore be exploited therapeutically. Here, we report a potent and selective lead small molecule, AVI-4206, that is effective in an in vivo model of SARS-CoV-2 infection. St

SUBMITTER: Suryawanshi RK 

PROVIDER: S-EPMC12629595 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature