Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures.

ABSTRACT: The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, emphasized the urgent need for development of novel antivirals. Small-molecule chemical probes offer both to reveal aspects of virus replication and to serve as leads for antiviral therapeutic development. Here, we report on the identification of amiloride-based small molecules that potently inhibit OC43 and SARS-CoV-2 replication through targeting of conserved structured elements within the viral 5′-end. Nuclear magnetic resonance–based structural studies revealed specific amiloride interactions with stem loops containing bulge like structures and were predicted to be strongly bound by the lead amilorides in retrospective docking studies. Amilorides represent the first antiviral small molecules that target RNA st

SUBMITTER: Zafferani M 

PROVIDER: S-EPMC8626076 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature