Bioinformatics and 3D Structural Analysis of the Coronavirus Main Protease Active Site Diversity

Journal Article · Fri May 13 00:00:00 EDT 2022 · FASEB Journal

DOI:https://doi.org/10.1096/fasebj.2022.36.S1.0R729· OSTI ID:1867737

Wu Wu, Amy ^[1]; Lubin, Joseph H. ^[2]; Olivas, Cassandra ^[3]; Zardecki, Christine ^[4]; Balogun, MaryAgnes ^[5]; Bacorn, Mickayla L. ^[6]; Khare, Sagar D. ^[2]; Burley, Stephen K. ^[4]

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1. Biology University of Puerto Rico Mayagüez Campus Cabo Rojo PR
2. IQB New Brunswick NJ
3. California State University, Stanislaus Stanislaus CA
4. IQB New Brunswick NJ, RCSB PDB New Brunswick NJ
5. Morgan State University Baltimore MD
6. University of Maryland, Baltimore County Baltimore MD

Coronaviruses (Coronaviridae) such as SARS‐CoV‐2 (severe acute respiratory syndrome coronavirus) and MERS‐CoV (Middle East respiratory syndrome coronavirus) have been the source of recent outbreaks and global health concerns. While vaccines have been essential for controlling the SARS‐CoV‐2 (COVID‐19) pandemic, it is uncertain whether they will be effective against future coronavirus strains. Therefore, identification or design of a broad‐spectrum drug that targets highly conserved regions of the main protease of multiple coronavirus strains is essential in the long term. As part of a virtual summer research experience with the RCSB PDB, bioinformatics tools were employed to predict and construct 3D models of the coronavirus main protease (MPro) using SARS‐CoV‐2 as the template, with a focus on mutational trends and active sites. This study focused on the active sites of MPro, a cysteine protease essential for viral assembly and replication. Sequence alignments and structure modeling of MPro structures has identified conserved regions across multiple coronavirus strains. Inhibition of MPro halts coronavirus replication, making it an ideal drug target, and studies of MPro may foster and accelerate the discovery of high affinity broad‐spectrum drugs.

• Sponsoring Organization: USDOE
• Grant/Contract Number: SC0019749
• OSTI ID: 1867737
• Journal Information: FASEB Journal, Journal Name: FASEB Journal Journal Issue: S1 Vol. 36; ISSN 0892-6638
• Publisher: FASEB
• Country of Publication: United States
• Language: English