Your browser doesn't support javascript.
Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp14/nsp10 exoribonuclease.
Canal, Berta; McClure, Allison W; Curran, Joseph F; Wu, Mary; Ulferts, Rachel; Weissmann, Florian; Zeng, Jingkun; Bertolin, Agustina P; Milligan, Jennifer C; Basu, Souradeep; Drury, Lucy S; Deegan, Tom D; Fujisawa, Ryo; Roberts, Emma L; Basier, Clovis; Labib, Karim; Beale, Rupert; Howell, Michael; Diffley, John F X.
  • Canal B; Chromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • McClure AW; Chromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Curran JF; Cell Cycle Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Wu M; High Throughput Screening, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Ulferts R; Cell Biology of Infection Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Weissmann F; Chromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Zeng J; Chromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Bertolin AP; Chromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Milligan JC; Chromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Basu S; Cell Cycle Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Drury LS; Chromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Deegan TD; The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
  • Fujisawa R; The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
  • Roberts EL; Cell Cycle Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Basier C; Cell Cycle Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Labib K; The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
  • Beale R; Cell Biology of Infection Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Howell M; High Throughput Screening, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
  • Diffley JFX; Chromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Biochem J ; 478(13): 2445-2464, 2021 07 16.
Article in English | MEDLINE | ID: covidwho-1290093
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
SARS-CoV-2 is a coronavirus that emerged in 2019 and rapidly spread across the world causing a deadly pandemic with tremendous social and economic costs. Healthcare systems worldwide are under great pressure, and there is an urgent need for effective antiviral treatments. The only currently approved antiviral treatment for COVID-19 is remdesivir, an inhibitor of viral genome replication. SARS-CoV-2 proliferation relies on the enzymatic activities of the non-structural proteins (nsp), which makes them interesting targets for the development of new antiviral treatments. With the aim to identify novel SARS-CoV-2 antivirals, we have purified the exoribonuclease/methyltransferase (nsp14) and its cofactor (nsp10) and developed biochemical assays compatible with high-throughput approaches to screen for exoribonuclease inhibitors. We have screened a library of over 5000 commercial compounds and identified patulin and aurintricarboxylic acid (ATA) as inhibitors of nsp14 exoribonuclease in vitro. We found that patulin and ATA inhibit replication of SARS-CoV-2 in a VERO E6 cell-culture model. These two new antiviral compounds will be valuable tools for further coronavirus research as well as potentially contributing to new therapeutic opportunities for COVID-19.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Viral Nonstructural Proteins / Drug Evaluation, Preclinical / Exoribonucleases / Viral Regulatory and Accessory Proteins / Small Molecule Libraries / SARS-CoV-2 Type of study: Diagnostic study / Prognostic study / Screening study Topics: Traditional medicine Limits: Animals Language: English Journal: Biochem J Year: 2021 Document Type: Article Affiliation country: Bcj20210198

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Viral Nonstructural Proteins / Drug Evaluation, Preclinical / Exoribonucleases / Viral Regulatory and Accessory Proteins / Small Molecule Libraries / SARS-CoV-2 Type of study: Diagnostic study / Prognostic study / Screening study Topics: Traditional medicine Limits: Animals Language: English Journal: Biochem J Year: 2021 Document Type: Article Affiliation country: Bcj20210198