Screening and druggability analysis of some plant metabolites against SARS-CoV-2: An integrative computational approach
The sudden outbreak of novel coronavirus has caused a global concern due to its infection rate and mortality. Despite extensive research, there are still no specific drugs or vaccines to combat SARS-CoV-2 infection. Hence, this study was designed to evaluate some plant-based active compounds for dru...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Informatics in Medicine Unlocked |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352914820303622 |
| _version_ | 1819072262068764672 |
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| author | Kazi Faizul Azim Sheikh Rashel Ahmed Anik Banik Md Mostafigur Rahman Khan Anamika Deb Saneya Risa Somana |
| author_facet | Kazi Faizul Azim Sheikh Rashel Ahmed Anik Banik Md Mostafigur Rahman Khan Anamika Deb Saneya Risa Somana |
| author_sort | Kazi Faizul Azim |
| collection | DOAJ |
| description | The sudden outbreak of novel coronavirus has caused a global concern due to its infection rate and mortality. Despite extensive research, there are still no specific drugs or vaccines to combat SARS-CoV-2 infection. Hence, this study was designed to evaluate some plant-based active compounds for drug candidacy against SARS-CoV-2 by using virtual screening methods and various computational analyses. A total of 27 plant metabolites were screened against SARS-CoV-2 main protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding domain, spike ecto-domain and HR2 domain using a molecular docking approach. Four metabolites, i.e., asiatic acid, avicularin, guajaverin, and withaferin showed maximum binding affinity with all key proteins in terms of lowest global binding energy. The crucial binding sites and drug surface hotspots were unravelled for each viral protein. The top candidates were further employed for ADME (absorption, distribution, metabolism, and excretion) analysis to investigate their drug profiles. Results suggest that none of the compounds render any undesirable consequences that could reduce their drug likeness properties. The analysis of toxicity pattern revealed no significant tumorigenic, mutagenic, irritating, or reproductive effects by the compounds. However, withaferin was comparatively toxic among the top four candidates with considerable cytotoxicity and immunotoxicity. Most of the target class by top drug candidates belonged to enzyme groups (e.g. oxidoreductases hydrolases, phosphatases). Moreover, results of drug similarity prediction revealed two approved structural analogs of Asiatic acid i.e. Hydrocortisone (DB00741) (previously used for SARS-CoV-1 and MERS) and Dinoprost-tromethamine (DB01160) from DrugBank. In addition, two other biologically active compounds, Mupirocin (DB00410) and Simvastatin (DB00641) could be an option for the treatment of viral infections. The study may pave the way to develop effective medications and preventive measure against SARS-CoV-2. Due to the encouraging results, we highly recommend further in vivo trials for the experimental validation of our findings. |
| first_indexed | 2024-12-21T17:34:56Z |
| format | Article |
| id | doaj.art-1b74090a4003407182506cc5fbcdd4ed |
| institution | Directory Open Access Journal |
| issn | 2352-9148 |
| language | English |
| last_indexed | 2024-12-21T17:34:56Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Informatics in Medicine Unlocked |
| spelling | doaj.art-1b74090a4003407182506cc5fbcdd4ed2022-12-21T18:55:48ZengElsevierInformatics in Medicine Unlocked2352-91482020-01-0120100367Screening and druggability analysis of some plant metabolites against SARS-CoV-2: An integrative computational approachKazi Faizul Azim0Sheikh Rashel Ahmed1Anik Banik2Md Mostafigur Rahman Khan3Anamika Deb4Saneya Risa Somana5Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, Bangladesh; Department of Microbial Biotechnology, Sylhet Agricultural University, Sylhet, 3100, Bangladesh; Corresponding author. Department of Microbial Biotechnology, Sylhet Agricultural University, Sylhet, 3100, Bangladesh.Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, Bangladesh; Department of Plant and Environmental Biotechnology, Sylhet Agricultural University, Sylhet, 3100, BangladeshFaculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, BangladeshFaculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, BangladeshFaculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, BangladeshFaculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, BangladeshThe sudden outbreak of novel coronavirus has caused a global concern due to its infection rate and mortality. Despite extensive research, there are still no specific drugs or vaccines to combat SARS-CoV-2 infection. Hence, this study was designed to evaluate some plant-based active compounds for drug candidacy against SARS-CoV-2 by using virtual screening methods and various computational analyses. A total of 27 plant metabolites were screened against SARS-CoV-2 main protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding domain, spike ecto-domain and HR2 domain using a molecular docking approach. Four metabolites, i.e., asiatic acid, avicularin, guajaverin, and withaferin showed maximum binding affinity with all key proteins in terms of lowest global binding energy. The crucial binding sites and drug surface hotspots were unravelled for each viral protein. The top candidates were further employed for ADME (absorption, distribution, metabolism, and excretion) analysis to investigate their drug profiles. Results suggest that none of the compounds render any undesirable consequences that could reduce their drug likeness properties. The analysis of toxicity pattern revealed no significant tumorigenic, mutagenic, irritating, or reproductive effects by the compounds. However, withaferin was comparatively toxic among the top four candidates with considerable cytotoxicity and immunotoxicity. Most of the target class by top drug candidates belonged to enzyme groups (e.g. oxidoreductases hydrolases, phosphatases). Moreover, results of drug similarity prediction revealed two approved structural analogs of Asiatic acid i.e. Hydrocortisone (DB00741) (previously used for SARS-CoV-1 and MERS) and Dinoprost-tromethamine (DB01160) from DrugBank. In addition, two other biologically active compounds, Mupirocin (DB00410) and Simvastatin (DB00641) could be an option for the treatment of viral infections. The study may pave the way to develop effective medications and preventive measure against SARS-CoV-2. Due to the encouraging results, we highly recommend further in vivo trials for the experimental validation of our findings.http://www.sciencedirect.com/science/article/pii/S2352914820303622SARS-CoV-2Plant metabolitesMain protease proteinsMolecular dockingADME analysisDrug target |
| spellingShingle | Kazi Faizul Azim Sheikh Rashel Ahmed Anik Banik Md Mostafigur Rahman Khan Anamika Deb Saneya Risa Somana Screening and druggability analysis of some plant metabolites against SARS-CoV-2: An integrative computational approach Informatics in Medicine Unlocked SARS-CoV-2 Plant metabolites Main protease proteins Molecular docking ADME analysis Drug target |
| title | Screening and druggability analysis of some plant metabolites against SARS-CoV-2: An integrative computational approach |
| title_full | Screening and druggability analysis of some plant metabolites against SARS-CoV-2: An integrative computational approach |
| title_fullStr | Screening and druggability analysis of some plant metabolites against SARS-CoV-2: An integrative computational approach |
| title_full_unstemmed | Screening and druggability analysis of some plant metabolites against SARS-CoV-2: An integrative computational approach |
| title_short | Screening and druggability analysis of some plant metabolites against SARS-CoV-2: An integrative computational approach |
| title_sort | screening and druggability analysis of some plant metabolites against sars cov 2 an integrative computational approach |
| topic | SARS-CoV-2 Plant metabolites Main protease proteins Molecular docking ADME analysis Drug target |
| url | http://www.sciencedirect.com/science/article/pii/S2352914820303622 |
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