التفاصيل البيبلوغرافية
| العنوان: |
Molecular docking-based virtual screening and computational investigations of biomolecules (curcumin analogs) as potential lead inhibitors for SARS-CoV-2 papain-like protease. |
| المؤلفون: |
Fakih, Taufik Muhammad, Ritmaleni, Zainul, Rahadian, Muchtaridi, Muchtaridi |
| المصدر: |
Pharmacia (0428-0296); 2024, Vol. 71 Issue 1, p1-19, 19p |
| مصطلحات موضوعية: |
SARS-CoV-2, CURCUMIN, BIOMOLECULES, MOLECULAR docking, PAPAIN, PROTEOLYTIC enzymes |
| مستخلص: |
In the effort to combat SARS-CoV-2 infection, researchers are currently exploring the repurposing of conventional antiviral drugs, despite their limited efficacy. The SARS-CoV-2 virus encodes a papain-like protease (PLpro), which not only plays a crucial role in viral replication but also cleaves ubiquitin and interferon-stimulated gene 15 protein (ISG15) from host proteins, making it a prime target for the development of new antiviral medications. In this study, we conducted a multi-step in silico screening to identify novel, noncovalent PLpro inhibitors. Curcumin, an antioxidant derived from turmeric rhizomes (Curcuma longa L.), has undergone extensive preclinical investigations and shown significant efficacy against viruses and other ailments in both laboratory and animal studies. However, the pharmacological limitations of curcumin have prompted the synthesis of numerous novel curcumin analogs, necessitating evaluation for their therapeutic potential. The selectivity of the top-scoring compounds was assessed through molecular docking studies and molecular dynamics simulations to determine their binding affinity to PLpro. As a result, we identified 20 potential, selective PLpro inhibitors, from which the top two compounds (THA111 and THHGV6) were selected based on their binding free energy values towards PLpro as estimated by MM-PBSA calculations. These selected candidates demonstrate promising activity against the protein, with binding free energy values ranging from approximately -105 to -108 kJ/mol, and largely adopt a similar binding mode to known noncovalent SARS-CoV-2 PLpro inhibitors (GRL0617 = -100.98 kJ/mol). We further propose these two most promising compounds for future in vitro evaluation. The findings for the top potential PLpro inhibitors have been deposited in a database (Curcumin Research Center) to aid research on anti-SARS-CoV-2 drugs. [ABSTRACT FROM AUTHOR] |
|
Copyright of Pharmacia (0428-0296) is the property of Bulgarian Pharmaceutical Scientific Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder