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.

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.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Epigenomic Medicine Program (TCK) is supported financially by McCord Research (Iowa, USA), which has a financial interest in dietary compounds described in this work. However, there is no conflict of interest with respect to the inhibition of the SARS-CoV-2 papain-like protease. The remaining co-authors also have no conflicts of interest.’
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