NDLI: Interrelated Mechanism by Which the Methide Quinone Celastrol, Obtained from the Roots of Tripterygium wilfordii, Inhibits Main Protease $3CL^{pro}$ of COVID-19 and Acts as Superoxide Radical Scavenger

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Interrelated Mechanism by Which the Methide Quinone Celastrol, Obtained from the Roots of Tripterygium wilfordii, Inhibits Main Protease $3CL^{pro}$ of COVID-19 and Acts as Superoxide Radical Scavenger

Content Provider	MDPI
Author	Caruso, Francesco Singh, Manrose Belli, Stuart Berinato, Molly Rossi, Miriam
Copyright Year	2020
Description	We describe the potential anti coronavirus disease 2019 (COVID-19) action of the methide quinone inhibitor, celastrol. The related methide quinone dexamethasone is, so far, among COVID-19 medications perhaps the most effective drug for patients with severe symptoms. We observe a parallel redox biology behavior between the antioxidant action of celastrol when scavenging the superoxide radical, and the adduct formation of celastrol with the main COVID-19 protease. The related molecular mechanism is envisioned using molecular mechanics and dynamics calculations. It proposes a covalent bond between the S(Cys145) amino acid thiolate and the celastrol A ring, assisted by proton transfers by His164 and His41 amino acids, and a π interaction from Met49 to the celastrol B ring. Specifically, celastrol possesses two moieties that are able to independently scavenge the superoxide radical: the carboxylic framework located at ring E, and the methide-quinone ring A. The latter captures the superoxide electron, releasing molecular oxygen, and is the feature of interest that correlates with the mechanism of COVID-19 inhibition. This unusual scavenging of the superoxide radical is described using density functional theory (DFT) methods, and is supported experimentally by cyclic voltammetry and X-ray diffraction.
Starting Page	9266
e-ISSN	14220067
DOI	10.3390/ijms21239266
Journal	International Journal of Molecular Sciences
Issue Number	23
Volume Number	21
Language	English
Publisher	MDPI
Publisher Date	2020-12-04
Access Restriction	Open
Subject Keyword	International Journal of Molecular Sciences Biochemistry and Molecular Biology Celastrol Methide Quinone Covid-19 Thiolate Protease Cyclic Voltammetry
Content Type	Text
Resource Type	Article

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