@article{822f19b3d3414886a63abc89d3149cac,
title = "SARS-CoV-2 Inhibitors Identified by Phenotypic Analysis of a Collection of Viral RNA-Binding Molecules",
abstract = "Antiviral agents are needed for the treatment of SARS-CoV-2 infections and to control other coronavirus outbreaks that may occur in the future. Here we report the identification and characterization of RNA-binding compounds that inhibit SARS-CoV-2 replication. The compounds were detected by screening a small library of antiviral compounds previously shown to bind HIV-1 or HCV RNA elements with a live-virus cellular assay detecting inhibition of SARS-CoV-2 replication. These experiments allowed detection of eight compounds with promising anti-SARS-CoV-2 activity in the sub-micromolar to micromolar range and wide selectivity indexes. Examination of the mechanism of action of three selected hit compounds excluded action on the entry or egress stages of the virus replication cycle and confirmed recognition by two of the molecules of conserved RNA elements of the SARS-CoV-2 genome, including the highly conserved S2m hairpin located in the 3{\textquoteright}-untranslated region of the virus. While further studies are needed to clarify the mechanism of action responsible for antiviral activity, these results facilitate the discovery of RNA-targeted antivirals and provide new chemical scaffolds for developing therapeutic agents against coronaviruses.",
keywords = "3{\textquoteright}UTR S2m hairpin, COVID-19, RNA, SARS-CoV-2, antiviral drug, coronavirus",
author = "Alvaro Simba-Lahuasi and {\'A}ngel Cantero-Camacho and Romel Rosales and McGovern, {Briana Lynn} and Rodr{\'i}guez, {M. Luis} and Vicente March{\'a}n and White, {Kris M.} and Adolfo Garc{\'i}a-Sastre and Jos{\'e} Gallego",
note = "Funding Information: This research was funded by La Caixa Banking Foundation of Spain (Caixaimpulse grant LCF/TR/CD20/52700004 to J.G.). We also acknowledge partial funding from Universidad Cat{\'o}lica de Valencia (predoctoral contract to A.S.-L.), Ministerio de Ciencia e Innovaci{\'o}n of Spain (10.13039/501100011033) and FEDER funds (grants RTI2018-093935-B-I00 to J.G. and PID2020-117508RB-I00 to V.M.), NIH NIAID (AViDD grant U19AI171443 to J.G. and A.G.-S.), and Generalitat Valenciana of Spain (grant PROMETEO 2021/036 to J.G.), as well as partial funding by CRIPT (Center for Research on Influenza Pathogenesis and Transmission), an NIH NIAID funded Center of Excellence for Influenza Research and Response (CEIRR, contract number 75N93021C00014), by a supplement to NIAID grant U19AI135972, by a supplement to DoD grant W81XWH-20-1-0270, by DARPA grant HR0011-19-2-319 0020, and by the JBP foundation and the OPP (research grant 2020-215611 (5384)) to A.G.-S. Publisher Copyright: {\textcopyright} 2022 by the authors.",
year = "2022",
month = dec,
doi = "10.3390/ph15121448",
language = "English",
volume = "15",
journal = "Pharmaceuticals",
issn = "1424-8247",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "12",
}