ABSTRACT
Scientists provide initial biochemical screenings with recombinant pure severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) main protease (Mpro) to discover prospective lead compounds for future coronavirus disease-19 (COVID-19) therapies because viral proteases, after polymerases, are the most likely targets for antiviral drug development. Quinones attach to cysteine-rich proteins, and COVID-19 central protease contains a Cys145-rich active site. The antiviral action of five embelin-containing plant products from Bangladesh against influenza virus A/Puerto Rico/8/34 (H1N1) MDCK infected cells was examined. All the evidence pointed to scaffold simplification and changing the shikonin naphthazarin nucleus as appropriate approaches for reducing shikonin cytotoxicity as a natural SARS-CoV-2 Mpro inhibitor. As a part of an extensive investigation of the biological properties of naphthoquinones with shikonin as a lead, and to contribute to drug discovery against COVID-19, the present study led to the development of juglone and its enhanced version as potent and effective Mpro inhibitors of SARS-CoV-2, which are promising antiviral medication candidates awaiting further analysis. A fluorescently labeled short peptide carrying a Q-S carboxyl link was used to test the inhibitory activity of synthesized quinones on Mpro of SARS-CoV-2. In the first library of chemicals, the capacity of several natural naphthoquinones and synthetic vitamin K3 was determined to inhibit SARS-CoV-2 Mpro at 10mM. According to a process described in a recent study on the suppression of SARS-CoV-2 Mpro by a methide quinone Celastrol, while attacking the carbonyl carbon, the development of the S–C covalent bond results in a tetrahedral output where the bond develops at the same carbon to which the hydroxy group is connected. © 2023 Elsevier Inc. All rights reserved.