The Virtual Screening and Molecular Docking Study of New Inhibitors for SARS-COV-2 Papain-Like Protease (PLpro)
Although global human mobility has normalized after the COVID-19 pandemic, the disease remains a major threat due to the emergence of new variants, keeping it a key target for drug development. Considerable efforts have been put to understand the disease, to create treatment options, and ultimately...
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| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Atatürk University
2025-05-01
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| Series: | Journal of Ata-Chem |
| Subjects: | |
| Online Access: | https://dergipark.org.tr/tr/download/article-file/4712370 |
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| Summary: | Although global human mobility has normalized after the COVID-19 pandemic, the disease remains a major threat due to the emergence of new variants, keeping it a key target for drug development. Considerable efforts have been put to understand the disease, to create treatment options, and ultimately to eradicate it. It has been shown that these viruses have the largest genome size among all known RNA viruses, with their genome consisting of an RNA strand enclosed in a protein coat. PLpro is an enzymatic protein which is necessary for the replication process of SARS-CoV-2 and during viral infection, it is essential in helping coronaviruses evade the host's innate immune defense. Consequently, targeting PLpro in antiviral drug development could be an effective approach to inhibit viral replication and interfere with signaling pathways in infected cells. This study aims to provide new potential inhibitor candidates for PLpro (PDB: 7LOS) by molecular modelling study. A total of over 2 million molecules from ZINC15 database have been screened against PLpro by structure- based virtual screening, followed by molecular docking. The docking scores of the top five ligands were in the range of -81.57 kcal/mol and -83.19 kcal/mol, which were much better than that of co-crystallized ligand Y97 (-58.25 kcal/mol). The docking results indicated that ligands interact with the key residues (Asp 164, Arg 166, and Glu167) in the active pocket of PLpro. H02 revealed some physicochemical properties as a potential hit according to the ADME results. |
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| ISSN: | 2822-3926 |