Structural analysis of the coronavirus main protease for the design of pan-variant inhibitors
Issued Date
2023-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85156181066
Pubmed ID
37120654
Journal Title
Scientific Reports
Volume
13
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.13 No.1 (2023)
Suggested Citation
Rungruangmaitree R., Phoochaijaroen S., Chimprasit A., Saparpakorn P., Pootanakit K., Tanramluk D. Structural analysis of the coronavirus main protease for the design of pan-variant inhibitors. Scientific Reports Vol.13 No.1 (2023). doi:10.1038/s41598-023-34305-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/81347
Title
Structural analysis of the coronavirus main protease for the design of pan-variant inhibitors
Author's Affiliation
Other Contributor(s)
Abstract
With the rapid rate of SARS-CoV-2 Main protease (Mpro) structures deposition, a computational method that can combine all the useful structural features becomes crucial. This research focuses on the frequently occurring atoms and residues to find a generalized strategy for inhibitor design given a large amount of protein complexes from SARS-CoV in contrast to SARS-CoV-2 Mpro. By superposing large numbers of the ligands onto the protein template and grid box, we can analyse which part of the structure is conserved from position-specific interaction for both data sets for the development of pan-Mpro antiviral design. The difference in conserved recognition sites from the crystal structures can be used to determine specificity determining residues for designing selective drugs. We can display pictures of the imaginary shape of the ligand by unionising all atoms from the ligand. We also pinpoint the most probable atom adjustments to imitate the frequently found densities from the ligand atoms statistics. With molecular docking, Molecular Dynamics simulation, and MM-PBSA methods, a carbonyl replacement at the nitrile warhead (N5) of Paxlovid’s Nirmatrelvir (PF-07321332) was suggested. By gaining insights into the selectivity and promiscuity regions for proteins and ligands, crucial residues are highlighted, and the antiviral design strategies are proposed.