Targeting protein homeostasis with small molecules as a strategy for the development of pan-coronavirus antiviral therapies.

ABSTRACT: The COVID-19 pandemic has created a global health crisis, with challenges arising from the ongoing evolution of the SARS-CoV-2 virus, the emergence of new strains, and the long-term effects of COVID-19. Aiming to overcome the development of viral resistance, our study here focused on developing broad-spectrum pan-coronavirus antiviral therapies by targeting host protein quality control mechanisms essential for viral replication. Screening an in-house compound library led to the discovery of three candidate compounds targeting cellular proteostasis. The three compounds are (1) the nucleotide analog cordycepin, (2) a benzothiozole analog, and (3) an acyldepsipeptide analog initially developed as part of a campaign to target the mitochondrial ClpP protease. These compounds demonstrated dose-d

SUBMITTER: Mao YQ 

PROVIDER: S-EPMC11543989 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature