Pharmacoinformatic study of inhibitory potentials of selected flavonoids against papain-like protease and 3-chymotrypsin-like protease of SARS-CoV-2

Background Inhibition of papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is projected to terminate its replication. Hence, these proteases represent viable therapeutic targets. Methods Sixty-one flavonoids with reported activities against other RNA viruses were selected and docked in PLpro and 3CLpro. Flavonoids with better binding energies compared to reference inhibitors (lopinavir and ritonavir) in their interaction with PLpro and 3CLpro were selected for drug-likeness and ADMET analysis. The best representative flavonoid for each protease from the ADMET filtering analysis was subjected to molecular dynamics simulations (MDS) and clustering analysis of the trajectory files. Results Licorice, ugonin M, procyanidin, silymarin, and gallocatechin gallate had better binding energies (-11.8, -10.1, -9.8, -9.7 and -9.6 kcal/mol respectively) with PLpro compared to lopinavir and ritonavir (-9.1 and -8.5 kcal/mol respectively). Also, isonymphaeol B, baicalin, abyssinone II, tomentin A, and apigetrin had better binding energies (-8.7, -8.3, -8.2, -8.1, and -8.1 kcal/mol respectively) with 3CLpro compared to lopinavir and ritonavir (-7.3 and -7.1 kcal/mol respectively). These flavonoids interacted with the proteases via hydrogen and non-hydrogen bonding. Of these flavonoids, silymarin and isonymphaeol B demonstrated most favourable combination of attributes in terms of binding energies, compliance with Lipinski rule for drug-likeness and favourable pharmacokinetics in silico. These two flavonoids exhibited appreciable degree of structural stability, maintaining strong interaction with residues in the different representative clusters selected during the MDS run. Conclusion Silymarin and isonymphaeol B are proposed for further studies as compounds with potential activities against SARS-CoV-2..

Highlights • Flavonoids displayed varying affinities for PLpro and 3CLpro of SARS-CoV-2 • They interacted via hydrogen and non-hydrogen bonds; nine and twenty-seven flavonoids had better binding affinities for PLpro and 3CLpro respectively than lopinavir and ritonavir • Silymarin and isonymphaeol B demonstrated most favourable combination of attributes in terms of binding energies, compliance with Lipinski rule for drug-likeness and favourable pharmacokinetics. • Silymarin and isonymphaeol B exhibited appreciable degree of structural stability, maintaining strong interaction with residues in the different representative clusters selected during the MDS run..

Medienart:	E-Artikel

Erscheinungsjahr:	2022
Erschienen:	2022

Enthalten in:	Zur Gesamtaufnahme - volume:8
Enthalten in:	Clinical phytoscience - 8(2022), 1 vom: 08. Sept.

Sprache:	Englisch

Beteiligte Personen:	Tijjani, Habibu [VerfasserIn] Adegunloye, Adegbenro P. [VerfasserIn] Uba, Auwalu [VerfasserIn] Adebayo, Joseph O. [VerfasserIn] Gyebi, Gideon A. [VerfasserIn] Ibrahim, Ibrahim M. [VerfasserIn]

Links:	Volltext [kostenfrei]

Themen:	3-Chymotrypsin-like protease Flavonoids In silico Papain-like protease SARS-CoV-2

Anmerkungen:	© The Author(s) 2022

doi:	10.1186/s40816-022-00347-y

funding:
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PPN (Katalog-ID):	SPR048037346