Site mapping and small molecule blind docking reveal a possible target site on the SARS-CoV-2 main protease dimer interface.

Clicks: 234
ID: 119897
2020
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #23 of 46 articles by views in Computational biology and chemistry

Most read Least read

Bar heights use a square-root scale.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
The SARS-CoV-2 virus is causing COVID-19 resulting in an ongoing pandemic with serious health, social, and economic implications. Much research is focused in repurposing or identifying new small molecules which may interact with viral or host-cell molecular targets. An important SARS-CoV-2 target is the main protease (M), and the peptidomimetic α-ketoamides represent prototypical experimental inhibitors. The protease is characterised by the dimerization of two monomers each which contains the catalytic dyad defined by Cys and His residues (active site). Dimerization yields the functional homodimer. Here, our aim was to investigate small molecules, including lopinavir and ritonavir, α-ketoamide 13b, and ebselen, for their ability to interact with the M. The sirtuin 1 agonist SRT1720 was also used in our analyses. Blind docking to each monomer individually indicated preferential binding of the ligands in the active site. Site-mapping of the dimeric protease indicated a highly reactive pocket in the dimerization region at the domain III apex. Blind docking consistently indicated a strong preference of ligand binding in domain III, away from the active site. Molecular dynamics simulations indicated that ligands docked both to the active site and in the dimerization region at the apex, formed relatively stable interactions. Overall, our findings do not obviate the superior potency with respect to inhibition of protease activity of covalently-linked inhibitors such as α-ketoamide 13b in the M active site. Nevertheless, along with those from others, our findings highlight the importance of further characterisation of the M active site and any potential allosteric sites.
Reference Key
liang2020sitecomputational Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Liang, Julia;Karagiannis, Chris;Pitsillou, Eleni;Darmawan, Kevion K;Ng, Ken;Hung, Andrew;Karagiannis, Tom C;
Journal Computational biology and chemistry
Year 2020
DOI
S1476-9271(20)30680-0
URL
Keywords
coronavirus covid-19 sars-cov-2 blind docking sars-cov-2 main protease site mapping

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.