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Clinical Phytoscience

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Open Access 01-12-2022 | Ritonavir | Original contribution

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

Authors: Habibu Tijjani, Adegbenro P. Adegunloye, Auwalu Uba, Joseph O. Adebayo, Gideon A. Gyebi, Ibrahim M. Ibrahim

Published in: Clinical Phytoscience | Issue 1/2022

Abstract

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.

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Title: Pharmacoinformatic study of inhibitory potentials of selected flavonoids against papain-like protease and 3-chymotrypsin-like protease of SARS-CoV-2
Authors: Habibu Tijjani
Adegbenro P. Adegunloye
Auwalu Uba
Joseph O. Adebayo
Gideon A. Gyebi
Ibrahim M. Ibrahim
Publication date: 01-12-2022
Publisher: Springer Berlin Heidelberg
Keywords: Ritonavir
SARS-CoV-2
Published in: Clinical Phytoscience / Issue 1/2022
Electronic ISSN: 2199-1197
DOI: https://doi.org/10.1186/s40816-022-00347-y

At a glance: The STEP trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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