SARS-CoV-2 Inhibitors Identified by Phenotypic Analysis of a Collection of Viral RNA-Binding Molecules
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 screenin...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/12/1448 |
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| author | Alvaro Simba-Lahuasi Ángel Cantero-Camacho Romel Rosales Briana Lynn McGovern M. Luis Rodríguez Vicente Marchán Kris M. White Adolfo García-Sastre José Gallego |
| author_facet | Alvaro Simba-Lahuasi Ángel Cantero-Camacho Romel Rosales Briana Lynn McGovern M. Luis Rodríguez Vicente Marchán Kris M. White Adolfo García-Sastre José Gallego |
| author_sort | Alvaro Simba-Lahuasi |
| collection | DOAJ |
| description | 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’-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. |
| first_indexed | 2024-03-09T15:59:24Z |
| format | Article |
| id | doaj.art-77d3fb81def04231933af5b1d52dd72e |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T15:59:24Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-77d3fb81def04231933af5b1d52dd72e2023-11-24T17:15:19ZengMDPI AGPharmaceuticals1424-82472022-11-011512144810.3390/ph15121448SARS-CoV-2 Inhibitors Identified by Phenotypic Analysis of a Collection of Viral RNA-Binding MoleculesAlvaro Simba-Lahuasi0Ángel Cantero-Camacho1Romel Rosales2Briana Lynn McGovern3M. Luis Rodríguez4Vicente Marchán5Kris M. White6Adolfo García-Sastre7José Gallego8Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia, 46001 Valencia, SpainCentro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia, 46001 Valencia, SpainDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartament de Química Inorgànica i Orgànica, Secció de Química Orgànica, Institut de Biomedicina (IBUB), Universitat de Barcelona (UB), 08028 Barcelona, SpainDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USACentro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia, 46001 Valencia, SpainAntiviral 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’-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.https://www.mdpi.com/1424-8247/15/12/1448antiviral drugcoronavirusCOVID-19RNASARS-CoV-23’UTR S2m hairpin |
| spellingShingle | Alvaro Simba-Lahuasi Ángel Cantero-Camacho Romel Rosales Briana Lynn McGovern M. Luis Rodríguez Vicente Marchán Kris M. White Adolfo García-Sastre José Gallego SARS-CoV-2 Inhibitors Identified by Phenotypic Analysis of a Collection of Viral RNA-Binding Molecules Pharmaceuticals antiviral drug coronavirus COVID-19 RNA SARS-CoV-2 3’UTR S2m hairpin |
| title | SARS-CoV-2 Inhibitors Identified by Phenotypic Analysis of a Collection of Viral RNA-Binding Molecules |
| title_full | SARS-CoV-2 Inhibitors Identified by Phenotypic Analysis of a Collection of Viral RNA-Binding Molecules |
| title_fullStr | SARS-CoV-2 Inhibitors Identified by Phenotypic Analysis of a Collection of Viral RNA-Binding Molecules |
| title_full_unstemmed | SARS-CoV-2 Inhibitors Identified by Phenotypic Analysis of a Collection of Viral RNA-Binding Molecules |
| title_short | SARS-CoV-2 Inhibitors Identified by Phenotypic Analysis of a Collection of Viral RNA-Binding Molecules |
| title_sort | sars cov 2 inhibitors identified by phenotypic analysis of a collection of viral rna binding molecules |
| topic | antiviral drug coronavirus COVID-19 RNA SARS-CoV-2 3’UTR S2m hairpin |
| url | https://www.mdpi.com/1424-8247/15/12/1448 |
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