Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells
Background and aim: The year 2020 begins with the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that cause the disease COVID-19, and continue till today. As of March 23, 2021, the outbreak has infected 124,313,054 worldwide with a total death of 2,735,707. The use of tradi...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Journal of Traditional and Complementary Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2225411021000389 |
| _version_ | 1819279328179912704 |
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| author | Seshu Vardhan Suban K. Sahoo |
| author_facet | Seshu Vardhan Suban K. Sahoo |
| author_sort | Seshu Vardhan |
| collection | DOAJ |
| description | Background and aim: The year 2020 begins with the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that cause the disease COVID-19, and continue till today. As of March 23, 2021, the outbreak has infected 124,313,054 worldwide with a total death of 2,735,707. The use of traditional medicines as an adjuvant therapy with western drugs can lower the fatality rate due to the COVID-19. Therefore, in silico molecular docking study was performed to search potential phytochemicals and drugs that can block the entry of SARS-CoV-2 into host cells by inhibiting the proteolytic cleavage activity of furin and TMPRSS2. Experimental procedure: The protein-protein docking of the host proteases furin and TMPRSS2 was carried out with the virus spike (S) protein to examine the conformational details and residues involved in the complex formation. Subsequently, a library of 163 ligands containing phytochemicals and drugs was virtually screened to propose potential hits that can inhibit the proteolytic cleavage activity of furin and TMPRSS2. Results and conclusion: The phytochemicals like limonin, gedunin, eribulin, pedunculagin, limonin glycoside and betunilic acid bind at the active site of both furin and TMPRSS2. Limonin and gedunin found mainly in the citrus fruits and neem showed the highest binding energy at the active site of furin and TMPRSS2, respectively. The polyphenols found in green tea can also be useful in suppressing the furin activity. Among the drugs, the drug nafamostat may be more beneficial than the camostat in suppressing the activity of TMPRSS2. |
| first_indexed | 2024-12-24T00:26:09Z |
| format | Article |
| id | doaj.art-7200a795f92a457bab756bba8c51700e |
| institution | Directory Open Access Journal |
| issn | 2225-4110 |
| language | English |
| last_indexed | 2024-12-24T00:26:09Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Traditional and Complementary Medicine |
| spelling | doaj.art-7200a795f92a457bab756bba8c51700e2022-12-21T17:24:25ZengElsevierJournal of Traditional and Complementary Medicine2225-41102022-01-01121615Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cellsSeshu Vardhan0Suban K. Sahoo1Department of Chemistry, Sardar Vallabhbhai National Institute of Technology (SVNIT), Surat, 395007, Gujarat, IndiaCorresponding author.; Department of Chemistry, Sardar Vallabhbhai National Institute of Technology (SVNIT), Surat, 395007, Gujarat, IndiaBackground and aim: The year 2020 begins with the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that cause the disease COVID-19, and continue till today. As of March 23, 2021, the outbreak has infected 124,313,054 worldwide with a total death of 2,735,707. The use of traditional medicines as an adjuvant therapy with western drugs can lower the fatality rate due to the COVID-19. Therefore, in silico molecular docking study was performed to search potential phytochemicals and drugs that can block the entry of SARS-CoV-2 into host cells by inhibiting the proteolytic cleavage activity of furin and TMPRSS2. Experimental procedure: The protein-protein docking of the host proteases furin and TMPRSS2 was carried out with the virus spike (S) protein to examine the conformational details and residues involved in the complex formation. Subsequently, a library of 163 ligands containing phytochemicals and drugs was virtually screened to propose potential hits that can inhibit the proteolytic cleavage activity of furin and TMPRSS2. Results and conclusion: The phytochemicals like limonin, gedunin, eribulin, pedunculagin, limonin glycoside and betunilic acid bind at the active site of both furin and TMPRSS2. Limonin and gedunin found mainly in the citrus fruits and neem showed the highest binding energy at the active site of furin and TMPRSS2, respectively. The polyphenols found in green tea can also be useful in suppressing the furin activity. Among the drugs, the drug nafamostat may be more beneficial than the camostat in suppressing the activity of TMPRSS2.http://www.sciencedirect.com/science/article/pii/S2225411021000389COVID-19SARS-CoV-2Protein-protein dockingMolecular dockingPhytochemicalsDrugs |
| spellingShingle | Seshu Vardhan Suban K. Sahoo Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells Journal of Traditional and Complementary Medicine COVID-19 SARS-CoV-2 Protein-protein docking Molecular docking Phytochemicals Drugs |
| title | Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells |
| title_full | Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells |
| title_fullStr | Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells |
| title_full_unstemmed | Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells |
| title_short | Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells |
| title_sort | virtual screening by targeting proteolytic sites of furin and tmprss2 to propose potential compounds obstructing the entry of sars cov 2 virus into human host cells |
| topic | COVID-19 SARS-CoV-2 Protein-protein docking Molecular docking Phytochemicals Drugs |
| url | http://www.sciencedirect.com/science/article/pii/S2225411021000389 |
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