| Autor: |
Panda SK; Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Berhampur 760010, Odisha, India., Sen Gupta PS; School of Biosciences and Bioengineering, D Y Patil International University (DYPIU), Akurdi, Pune 411044, Maharashtra, India., Karmakar S; Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Berhampur 760010, Odisha, India., Biswal S; Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Berhampur 760010, Odisha, India., Mahanandia NC; Division of Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, Pusa 110012, New Delhi, India., Rana MK; Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Berhampur 760010, Odisha, India. |
| Abstrakt: |
To date, mechanistic insights into many clinical drugs against COVID-19 remain unexplored. Dexamethasone, a corticosteroid, is one of them. While treating the entire corticosteroid database, including vitamins D2 and D3, with cutting-edge computational techniques, several intriguing results are unfolded. From the top-notch candidates, dexamethasone is likely to inhibit the viral main protease (Mpro), with vitamin D3 exhibiting multitarget [Mpro, papain-like protease (PLpro), and nucleocapsid protein (N-pro)] roles and ciclesonide's dynamic flipping disinterring a cryptic allosteric site in the PLpro enzyme. The results rationalize why these drugs improve the health of COVID-19 patients. Understanding an enzyme's secret binding site is essential to understanding how the enzyme works and how to inhibit its function. Ciclesonide's allosteric inhibition could not only jeopardize PLpro's catalytic role in polyprotein processing but also make it less vulnerable to the host body's defense machinery. Hotspot residues in the identified allosteric site could be considered for effective therapeutic designs against PLpro. |
