Author(s)
Nicola De Maio
Scientist in Molecular Evolution, European Bioinformatic Institute (EMBL-EBI), Cambridge
Published 1 Project
Matthieu Schapira
Associate Professor, University of Toronto
Published 8 Projects
Bioinformatics Biochemistry Pharmacology And Toxicology Cell Biology
Content
Video Abstract (AI generated) (01:35) Paper Preprint Supplementary informationIn the absence of effective treatment, COVID-19 is likely to remain a global disease burden. Compounding this threat is the near certainty that novel coronaviruses with pandemic potential will emerge in years to come. Pan-coronavirus drugs - agents active against both SARS-CoV-2 and other coronaviruses - would address both threats. A strategy to develop such broad-spectrum inhibitors is to pharmacologically target binding sites on SARS-CoV-2 proteins that are highly conserved in other known coronaviruses, the assumption being that any selective pressure to keep a site conserved across past viruses will apply to future ones. Here, we systematically mapped druggable binding pockets on the experimental structure of fifteen SARS-CoV-2 proteins and analyzed their variation across twenty-seven - and {beta}-coronaviruses and across thousands of SARS-CoV-2 samples from COVID-19 patients. We find that the two most conserved druggable sites are a pocket overlapping the RNA binding site of the helicase nsp13, and the catalytic site of the RNA-dependent RNA polymerase nsp12, both components of the viral replication-transcription complex. We present the data on a public web portal (https://www.thesgc.org/SARSCoV2_pocketome/) where users can interactively navigate individual protein structures and view the genetic variability of drug binding pockets in 3D.
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Setayesh Yazdani. (2021, Sep 25).The SARS-CoV-2 replication-transcription complex is a priority target for broad-spectrum pan-coronavirus drugs[Video]. Scitok. https://scitok.com/project/p/7ea536fb
Yazdani Setayesh. "The SARS-CoV-2 replication-transcription complex is a priority target for broad-spectrum pan-coronavirus drugs" Scitok, uploaded by Yazdani Setayesh, 25 Sep, 2021, https://scitok.com/project/p7ea536fb
Setayesh Yazdani. "The SARS-CoV-2 replication-transcription complex is a priority target for broad-spectrum pan-coronavirus drugs" Scitok. (Sep 25, 2021). https://scitok.com/project/p/7ea536fb
Setayesh Yazdani (Sep 25, 2021). The SARS-CoV-2 replication-transcription complex is a priority target for broad-spectrum pan-coronavirus drugs Scitok. https://scitok.com/project/p/7ea536fb
Setayesh Yazdani. The SARS-CoV-2 replication-transcription complex is a priority target for broad-spectrum pan-coronavirus drugs[video]. 2021 Sep 25. https://scitok.com/project/p/7ea536fb
@online{al2006link, title={ The SARS-CoV-2 replication-transcription complex is a priority target for broad-spectrum pan-coronavirus drugs }, author={ Yazdani, Setayesh }, organization={Scitok}, month={ Sep }, day={ 25 }, year={ 2021 }, url = {https://scitok.com/project/p/7ea536fb}, }