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Bioinformatics and 3D Structural Analysis of the Coronavirus Main Protease Active Site Diversity
Author(s) -
Wu Wu Amy,
Lubin Joseph H.,
Olivas Cassandra,
Zardecki Christine,
Balogun MaryAgnes,
Bacorn Mickayla L.,
Khare Sagar D.,
Burley Stephen K.
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.0r729
Subject(s) - coronavirus , protease , middle east respiratory syndrome coronavirus , virology , computational biology , coronaviridae , biology , viral replication , protein data bank (rcsb pdb) , drug discovery , covid-19 , bioinformatics , virus , medicine , enzyme , biochemistry , disease , pathology , infectious disease (medical specialty)
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.