Theaflavin 3-gallate inhibits the main protease (Mpro) of SARS-CoV-2 and reduces its count in vitro
Abstract The main protease (Mpro) of SARS-CoV-2 has been recognized as an attractive drug target because of its central role in viral replication. Our previous preliminary molecular docking studies showed that theaflavin 3-gallate (a natural bioactive molecule derived from theaflavin and found in hi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-17558-5 |
| _version_ | 1811222411482234880 |
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| author | Mahima Chauhan Vijay Kumar Bhardwaj Asheesh Kumar Vinod Kumar Pawan Kumar M. Ghalib Enayathullah Jessie Thomas Joel George Bokara Kiran Kumar Rituraj Purohit Arun Kumar Sanjay Kumar |
| author_facet | Mahima Chauhan Vijay Kumar Bhardwaj Asheesh Kumar Vinod Kumar Pawan Kumar M. Ghalib Enayathullah Jessie Thomas Joel George Bokara Kiran Kumar Rituraj Purohit Arun Kumar Sanjay Kumar |
| author_sort | Mahima Chauhan |
| collection | DOAJ |
| description | Abstract The main protease (Mpro) of SARS-CoV-2 has been recognized as an attractive drug target because of its central role in viral replication. Our previous preliminary molecular docking studies showed that theaflavin 3-gallate (a natural bioactive molecule derived from theaflavin and found in high abundance in black tea) exhibited better docking scores than repurposed drugs (Atazanavir, Darunavir, Lopinavir). In this study, conventional and steered MD-simulations analyses revealed stronger interactions of theaflavin 3-gallate with the active site residues of Mpro than theaflavin and a standard molecule GC373 (a known inhibitor of Mpro and novel broad-spectrum anti-viral agent). Theaflavin 3-gallate inhibited Mpro protein of SARS-CoV-2 with an IC50 value of 18.48 ± 1.29 μM. Treatment of SARS-CoV-2 (Indian/a3i clade/2020 isolate) with 200 μM of theaflavin 3-gallate in vitro using Vero cells and quantifying viral transcripts demonstrated reduction of viral count by 75% (viral particles reduced from Log106.7 to Log106.1). Overall, our findings suggest that theaflavin 3-gallate effectively targets the Mpro thus limiting the replication of the SARS-CoV-2 virus in vitro. |
| first_indexed | 2024-04-12T08:15:26Z |
| format | Article |
| id | doaj.art-2f784c3faa38471da66738e0c6fd1421 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T08:15:26Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2f784c3faa38471da66738e0c6fd14212022-12-22T03:40:49ZengNature PortfolioScientific Reports2045-23222022-07-0112111210.1038/s41598-022-17558-5Theaflavin 3-gallate inhibits the main protease (Mpro) of SARS-CoV-2 and reduces its count in vitroMahima Chauhan0Vijay Kumar Bhardwaj1Asheesh Kumar2Vinod Kumar3Pawan Kumar4M. Ghalib Enayathullah5Jessie Thomas6Joel George7Bokara Kiran Kumar8Rituraj Purohit9Arun Kumar10Sanjay Kumar11Biotechnology Division, CSIR-Institute of Himalayan Bioresource TechnologyBiotechnology Division, CSIR-Institute of Himalayan Bioresource TechnologyBiotechnology Division, CSIR-Institute of Himalayan Bioresource TechnologyBiotechnology Division, CSIR-Institute of Himalayan Bioresource TechnologyAcademy of Scientific and Innovative ResearchCSIR-Center for Cellular and Molecular BiologyCSIR-Center for Cellular and Molecular BiologyCSIR-Center for Cellular and Molecular BiologyCSIR-Center for Cellular and Molecular BiologyBiotechnology Division, CSIR-Institute of Himalayan Bioresource TechnologyBiotechnology Division, CSIR-Institute of Himalayan Bioresource TechnologyBiotechnology Division, CSIR-Institute of Himalayan Bioresource TechnologyAbstract The main protease (Mpro) of SARS-CoV-2 has been recognized as an attractive drug target because of its central role in viral replication. Our previous preliminary molecular docking studies showed that theaflavin 3-gallate (a natural bioactive molecule derived from theaflavin and found in high abundance in black tea) exhibited better docking scores than repurposed drugs (Atazanavir, Darunavir, Lopinavir). In this study, conventional and steered MD-simulations analyses revealed stronger interactions of theaflavin 3-gallate with the active site residues of Mpro than theaflavin and a standard molecule GC373 (a known inhibitor of Mpro and novel broad-spectrum anti-viral agent). Theaflavin 3-gallate inhibited Mpro protein of SARS-CoV-2 with an IC50 value of 18.48 ± 1.29 μM. Treatment of SARS-CoV-2 (Indian/a3i clade/2020 isolate) with 200 μM of theaflavin 3-gallate in vitro using Vero cells and quantifying viral transcripts demonstrated reduction of viral count by 75% (viral particles reduced from Log106.7 to Log106.1). Overall, our findings suggest that theaflavin 3-gallate effectively targets the Mpro thus limiting the replication of the SARS-CoV-2 virus in vitro.https://doi.org/10.1038/s41598-022-17558-5 |
| spellingShingle | Mahima Chauhan Vijay Kumar Bhardwaj Asheesh Kumar Vinod Kumar Pawan Kumar M. Ghalib Enayathullah Jessie Thomas Joel George Bokara Kiran Kumar Rituraj Purohit Arun Kumar Sanjay Kumar Theaflavin 3-gallate inhibits the main protease (Mpro) of SARS-CoV-2 and reduces its count in vitro Scientific Reports |
| title | Theaflavin 3-gallate inhibits the main protease (Mpro) of SARS-CoV-2 and reduces its count in vitro |
| title_full | Theaflavin 3-gallate inhibits the main protease (Mpro) of SARS-CoV-2 and reduces its count in vitro |
| title_fullStr | Theaflavin 3-gallate inhibits the main protease (Mpro) of SARS-CoV-2 and reduces its count in vitro |
| title_full_unstemmed | Theaflavin 3-gallate inhibits the main protease (Mpro) of SARS-CoV-2 and reduces its count in vitro |
| title_short | Theaflavin 3-gallate inhibits the main protease (Mpro) of SARS-CoV-2 and reduces its count in vitro |
| title_sort | theaflavin 3 gallate inhibits the main protease mpro of sars cov 2 and reduces its count in vitro |
| url | https://doi.org/10.1038/s41598-022-17558-5 |
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