A new paper from Covid19-NMR participants was recently published in “Science Advances“. RNA-targeted antivirals have been identified using cytotoxicity and SARS-CoV-2 antiviral assays, NMR profiling, virtual ligand screening and small-molecule docking.
Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures
The current pandemic and likelihood of future coronavirus pandemics, emphasized the urgent need for novel antivirals. In this paper, the authors report on the identification of amiloride-based small molecules that potently inhibit OC43 and SARS-CoV-2 replication. NMR–based structural studies further revealed specific amiloride interactions with stem loops containing bulge like structures (SL1, SL4, SL5a, and SL6) 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′ UTR and proximal region of the CoV genomes and will thereby serve as chemical probes to further understand CoV RNA biology and develop other specific CoV RNA–targeted antivirals.
Many thanks to all authors for their contribution to this great teamwork!