An in silico approach to develop potential therapies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
A deadly respiratory disease Middle East Respiratory Syndrome (MERS) is caused by a perilous virus known as MERS-CoV, which has a severe impact on human health. Currently, there is no approved vaccine, prophylaxis, or antiviral therapeutics for preventing MERS-CoV infection. Due to its inexorable an...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024018681 |
| _version_ | 1797267753425436672 |
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| author | Suvro Biswas Mohasana Akter Mita Shamima Afrose Md. Robiul Hasan Mst. Sharmin Sultana Shimu Shahriar Zaman Md. Abu Saleh |
| author_facet | Suvro Biswas Mohasana Akter Mita Shamima Afrose Md. Robiul Hasan Mst. Sharmin Sultana Shimu Shahriar Zaman Md. Abu Saleh |
| author_sort | Suvro Biswas |
| collection | DOAJ |
| description | A deadly respiratory disease Middle East Respiratory Syndrome (MERS) is caused by a perilous virus known as MERS-CoV, which has a severe impact on human health. Currently, there is no approved vaccine, prophylaxis, or antiviral therapeutics for preventing MERS-CoV infection. Due to its inexorable and integral role in the maturation and replication of the MERS-CoV virus, the 3C-like protease is unavoidly a viable therapeutic target. In this study, 2369 phytoconstituents were enlisted from Japanese medicinal plants, and these compounds were screened against 3C-like protease to identify feasible inhibitors. The best three compounds were identified as Kihadanin B, Robustaflavone, and 3-beta-O- (trans-p-Coumaroyl) maslinic acid, with binding energies of −9.8, −9.4, and −9.2 kcal/mol, respectively. The top three potential candidates interacted with several active site residues in the targeted protein, including Cys145, Met168, Glu169, Ala171, and Gln192. The best three compounds were assessed by in silico technique to determine their drug-likeness properties, and they exhibited the least harmful features and the greatest drug-like qualities. Various descriptors, such as solvent-accessible surface area, root-mean-square fluctuation, root-mean-square deviation, hydrogen bond, and radius of gyration, validated the stability and firmness of the protein-ligand complexes throughout the 100ns molecular dynamics simulation. Moreover, the top three compounds exhibited better binding energy along with better stability and firmness than the inhibitor (Nafamostat), which was further confirmed by the binding free energy calculation. Therefore, this computational investigation could aid in the development of efficient therapeutics for life-threatening MERS-CoV infections. |
| first_indexed | 2024-03-08T00:49:15Z |
| format | Article |
| id | doaj.art-94d1e5d15f3246a193d57181796bbd97 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-25T01:21:36Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-94d1e5d15f3246a193d57181796bbd972024-03-09T09:26:19ZengElsevierHeliyon2405-84402024-02-01104e25837An in silico approach to develop potential therapies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV)Suvro Biswas0Mohasana Akter Mita1Shamima Afrose2Md. Robiul Hasan3Mst. Sharmin Sultana Shimu4Shahriar Zaman5Md. Abu Saleh6Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, BangladeshDepartment of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, BangladeshDepartment of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, BangladeshDepartment of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, BangladeshDepartment of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, BangladeshMicrobiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, BangladeshMicrobiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh; Corresponding author.A deadly respiratory disease Middle East Respiratory Syndrome (MERS) is caused by a perilous virus known as MERS-CoV, which has a severe impact on human health. Currently, there is no approved vaccine, prophylaxis, or antiviral therapeutics for preventing MERS-CoV infection. Due to its inexorable and integral role in the maturation and replication of the MERS-CoV virus, the 3C-like protease is unavoidly a viable therapeutic target. In this study, 2369 phytoconstituents were enlisted from Japanese medicinal plants, and these compounds were screened against 3C-like protease to identify feasible inhibitors. The best three compounds were identified as Kihadanin B, Robustaflavone, and 3-beta-O- (trans-p-Coumaroyl) maslinic acid, with binding energies of −9.8, −9.4, and −9.2 kcal/mol, respectively. The top three potential candidates interacted with several active site residues in the targeted protein, including Cys145, Met168, Glu169, Ala171, and Gln192. The best three compounds were assessed by in silico technique to determine their drug-likeness properties, and they exhibited the least harmful features and the greatest drug-like qualities. Various descriptors, such as solvent-accessible surface area, root-mean-square fluctuation, root-mean-square deviation, hydrogen bond, and radius of gyration, validated the stability and firmness of the protein-ligand complexes throughout the 100ns molecular dynamics simulation. Moreover, the top three compounds exhibited better binding energy along with better stability and firmness than the inhibitor (Nafamostat), which was further confirmed by the binding free energy calculation. Therefore, this computational investigation could aid in the development of efficient therapeutics for life-threatening MERS-CoV infections.http://www.sciencedirect.com/science/article/pii/S2405844024018681PhytoconstituentsMERS-CoV3CLproMolecular dockingADMETMolecular dynamics simulation |
| spellingShingle | Suvro Biswas Mohasana Akter Mita Shamima Afrose Md. Robiul Hasan Mst. Sharmin Sultana Shimu Shahriar Zaman Md. Abu Saleh An in silico approach to develop potential therapies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Heliyon Phytoconstituents MERS-CoV 3CLpro Molecular docking ADMET Molecular dynamics simulation |
| title | An in silico approach to develop potential therapies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) |
| title_full | An in silico approach to develop potential therapies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) |
| title_fullStr | An in silico approach to develop potential therapies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) |
| title_full_unstemmed | An in silico approach to develop potential therapies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) |
| title_short | An in silico approach to develop potential therapies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) |
| title_sort | in silico approach to develop potential therapies against middle east respiratory syndrome coronavirus mers cov |
| topic | Phytoconstituents MERS-CoV 3CLpro Molecular docking ADMET Molecular dynamics simulation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024018681 |
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