Inhibition of interferon-stimulated gene 15 and lysine 48-linked ubiquitin binding to the SARS-CoV-2 papain-like protease by small molecules: In silico studies

Eleni Pitsillou; Julia Liang; Andrew Hung; Tom C Karagiannis

doi:10.1016/j.cplett.2021.138468

Inhibition of interferon-stimulated gene 15 and lysine 48-linked ubiquitin binding to the SARS-CoV-2 papain-like protease by small molecules: In silico studies

Chem Phys Lett. 2021 May 16:771:138468. doi: 10.1016/j.cplett.2021.138468. Epub 2021 Mar 8.

Authors

Eleni Pitsillou^{1

2}, Julia Liang^{1

2}, Andrew Hung², Tom C Karagiannis^{1

3}

Affiliations

¹ Epigenomic Medicine, Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
² School of Science, College of Science, Engineering & Health, RMIT University, VIC 3001, Australia.
³ Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3052, Australia.

Abstract

The SARS-CoV-2 papain-like protease (PL^pro) is a suitable target for drug development, and its deubiquitinating and deISGylating activities have also been reported. In this study, molecular docking was used to investigate the binding properties of a selection of dietary compounds and naphthalene-based inhibitors to the previously characterised binding site of GRL-0617. The structures of the SARS-CoV-2 and SARS-CoV PL^pro in complex with interferon-stimulated gene 15 (ISG15) and lysine 48 (K48)-linked diubiquitin were utilised. To predict whether compounds could potentially interfere with the binding of these cellular modifiers, docking was conducted in the absence and presence of ISG15 and K48-linked diubiquitin.

Keywords: COVID-19; Coronavirus; Dietary compounds; Molecular docking; Naphthalene-based inhibitors; Papain-like protease; SARS-CoV-2; deISGylating activity; deubiquitinase activity.