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

Journal Article (Journal Article)

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 structures within the 5′ untranslated regions and proximal region of the CoV genomes. These molecules will serve as chemical probes to further understand CoV RNA biology and can pave the way for the development of specific CoV RNA–targeted antivirals.

Full Text

Duke Authors

Cited Authors

  • Zafferani, M; Haddad, C; Luo, L; Davila-Calderon, J; Chiu, L-Y; Mugisha, CS; Monaghan, AG; Kennedy, AA; Yesselman, JD; Gifford, RJ; Tai, AW; Kutluay, SB; Li, M-L; Brewer, G; Tolbert, BS; Hargrove, AE

Published Date

  • November 2021

Published In

Volume / Issue

  • 7 / 48

Start / End Page

  • eabl6096 -

PubMed ID

  • 34826236

Pubmed Central ID

  • PMC8626076

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

International Standard Serial Number (ISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.abl6096


  • eng