Sequence Characterization and Molecular Modeling of Clinically Relevant Variants of the SARS-CoV‑2 Main Protease

• Published in: Biochemistry (Easton) Vol. 59; no. 39; pp. 3741 - 3756
• Main Authors: Cross, Thomas J, Takahashi, Gemma R, Diessner, Elizabeth M, Crosby, Marquise G, Farahmand, Vesta, Zhuang, Shannon, Butts, Carter T, Martin, Rachel W
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 06.10.2020
• Subjects: active sites; Betacoronavirus - enzymology; Betacoronavirus - genetics; Catalytic Domain; cohesion; design; Drug Discovery; drugs; Evolution, Molecular; Humans; hydrophobicity; Models, Molecular; molecular models; Molecular Structure; Mutation; Phylogeny; prediction; Protease Inhibitors - chemistry; protein structure; proteinases; SARS-CoV-2; selection pressure; sequence analysis; Sequence Analysis, Protein; Viral Nonstructural Proteins - antagonists & inhibitors; Viral Nonstructural Proteins - genetics; virus replication; viruses

The SARS-CoV-2 main protease (M pro ) is essential to viral replication and cleaves highly specific substrate sequences, making it an obvious target for inhibitor design. However, as for any virus, SARS-CoV-2 is subject to constant neutral drift and selection pressure, with new M pro mutations arisi...