Virtual Screening and Inhibition of Middle East Respiratory Syndrome Coronavirus Replication by Targeting Papain-like Protease

Authors

Mahmoud Kandeel^{1, 2, *,} , Byoung Kwon Park^3, , Mohamed A. Morsy^{4, 5,} , Katharigatta N. Venugopala^{4, 6,} , Kentaro Oh-hashi⁷, Mohammed Al-Nazawi¹, Hyung-Joo Kwon^3,

¹Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia

²Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt

³Department of Microbiology, Hallym University College of Medicine, Chuncheon 24252, South Korea

⁴Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia

⁵Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt

⁶Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4000, South Africa

⁷Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan

^*Corresponding author. Email: mkandeel@kfu.edu.sa

DOI

10.2991/dsahmj.k.210921.001How to use a DOI?

Keywords

MERS-CoV; papain-like protease; antiviral agents; virtual screening; plaque

Abstract

Infection by the emerging, potentially zoonotic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) presents a severe health hazard to humans and is often fatal. Given the lack of particular medicines against MERS-CoV, drug discovery studies are needed to bridge this knowledge gap. In this study, we introduce virtual screening-guided identification of MERS-CoV Papain-like Protease (PL^pro)-binding drugs. After a two-step virtual screening method, enzyme assays and antiviral testing with a MERS-CoV plaque reduction assay were used to further investigate the five compounds with the highest computational score. The top five screened compounds showed a 10.2–40% decrease in MERS-CoV PL^pro activity. The top two compounds showed promising inhibition of MERS-CoV replication, reducing virus plaque formation by 30.6% and 24%. Compounds 1 and 4 in this study can be further modified to target binding with MERS-CoV PL^pro active triad residues. Furthermore, the compounds produced stable interaction with the protein and protein conformation. With their reported inhibition of MERS-CoV enzyme and virus replication, supported by favorable absorption, distribution, metabolism, and excretion and toxicity profiles, the two reported benzimidazole and piperazine derivatives could be considered lead compounds against MERS-CoV.

Copyright

© 2021 Dr. Sulaiman Al Habib Medical Group. Publishing services by Atlantis Press International B.V.

Open Access

This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

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TY  - JOUR
AU  - Mahmoud Kandeel
AU  - Byoung Kwon Park
AU  - Mohamed A. Morsy
AU  - Katharigatta N. Venugopala
AU  - Kentaro Oh-hashi
AU  - Mohammed Al-Nazawi
AU  - Hyung-Joo Kwon
PY  - 2021
DA  - 2021/11/19
TI  - Virtual Screening and Inhibition of Middle East Respiratory Syndrome Coronavirus Replication by Targeting Papain-like Protease
JO  - Dr. Sulaiman Al Habib Medical Journal
SP  - 179
EP  - 187
VL  - 3
IS  - 4
SN  - 2590-3349
UR  - https://doi.org/10.2991/dsahmj.k.210921.001
DO  - 10.2991/dsahmj.k.210921.001
ID  - Kandeel2021
ER  -