A ricin-based peptide BRIP from Hordeum vulgare inhibits Mpro of SARS-CoV-2
Abstract COVID-19 pandemic caused by SARS-CoV-2 led to the research aiming to find the inhibitors of this virus. Towards this world problem, an attempt was made to identify SARS-CoV-2 main protease (Mpro) inhibitory peptides from ricin domains. The ricin-based peptide from barley (BRIP) was able to...
| 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/s41598-022-15977-y |
| _version_ | 1818162972820766720 |
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| author | Prakriti Kashyap Vijay Kumar Bhardwaj Mahima Chauhan Varun Chauhan Asheesh Kumar Rituraj Purohit Arun Kumar Sanjay Kumar |
| author_facet | Prakriti Kashyap Vijay Kumar Bhardwaj Mahima Chauhan Varun Chauhan Asheesh Kumar Rituraj Purohit Arun Kumar Sanjay Kumar |
| author_sort | Prakriti Kashyap |
| collection | DOAJ |
| description | Abstract COVID-19 pandemic caused by SARS-CoV-2 led to the research aiming to find the inhibitors of this virus. Towards this world problem, an attempt was made to identify SARS-CoV-2 main protease (Mpro) inhibitory peptides from ricin domains. The ricin-based peptide from barley (BRIP) was able to inhibit Mpro in vitro with an IC50 of 0.52 nM. Its low and no cytotoxicity upto 50 µM suggested its therapeutic potential against SARS-CoV-2. The most favorable binding site on Mpro was identified by molecular docking and steered molecular dynamics (MD) simulations. The Mpro-BRIP interactions were further investigated by evaluating the trajectories for microsecond timescale MD simulations. The structural parameters of Mpro-BRIP complex were stable, and the presence of oppositely charged surfaces on the binding interface of BRIP and Mpro complex further contributed to the overall stability of the protein-peptide complex. Among the components of thermodynamic binding free energy, Van der Waals and electrostatic contributions were most favorable for complex formation. Our findings provide novel insight into the area of inhibitor development against COVID-19. |
| first_indexed | 2024-12-11T16:42:10Z |
| format | Article |
| id | doaj.art-107be460b7764ca996b4c081ebaade7c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-11T16:42:10Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-107be460b7764ca996b4c081ebaade7c2022-12-22T00:58:17ZengNature PortfolioScientific Reports2045-23222022-07-0112111110.1038/s41598-022-15977-yA ricin-based peptide BRIP from Hordeum vulgare inhibits Mpro of SARS-CoV-2Prakriti Kashyap0Vijay Kumar Bhardwaj1Mahima Chauhan2Varun Chauhan3Asheesh Kumar4Rituraj Purohit5Arun Kumar6Sanjay Kumar7Biotechnology Division, CSIR-Institute of Himalayan Bioresource TechnologyBiotechnology Division, CSIR-Institute of Himalayan Bioresource TechnologyBiotechnology Division, CSIR-Institute of Himalayan Bioresource TechnologyCovid-19 Testing Facility, Dietetics & Nutrition Technology Division, Council of Scientific and Industrial Research-Institute of Himalayan Bioresource Technology (CSIR-IHBT)Biotechnology 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 TechnologyAbstract COVID-19 pandemic caused by SARS-CoV-2 led to the research aiming to find the inhibitors of this virus. Towards this world problem, an attempt was made to identify SARS-CoV-2 main protease (Mpro) inhibitory peptides from ricin domains. The ricin-based peptide from barley (BRIP) was able to inhibit Mpro in vitro with an IC50 of 0.52 nM. Its low and no cytotoxicity upto 50 µM suggested its therapeutic potential against SARS-CoV-2. The most favorable binding site on Mpro was identified by molecular docking and steered molecular dynamics (MD) simulations. The Mpro-BRIP interactions were further investigated by evaluating the trajectories for microsecond timescale MD simulations. The structural parameters of Mpro-BRIP complex were stable, and the presence of oppositely charged surfaces on the binding interface of BRIP and Mpro complex further contributed to the overall stability of the protein-peptide complex. Among the components of thermodynamic binding free energy, Van der Waals and electrostatic contributions were most favorable for complex formation. Our findings provide novel insight into the area of inhibitor development against COVID-19.https://doi.org/10.1038/s41598-022-15977-y |
| spellingShingle | Prakriti Kashyap Vijay Kumar Bhardwaj Mahima Chauhan Varun Chauhan Asheesh Kumar Rituraj Purohit Arun Kumar Sanjay Kumar A ricin-based peptide BRIP from Hordeum vulgare inhibits Mpro of SARS-CoV-2 Scientific Reports |
| title | A ricin-based peptide BRIP from Hordeum vulgare inhibits Mpro of SARS-CoV-2 |
| title_full | A ricin-based peptide BRIP from Hordeum vulgare inhibits Mpro of SARS-CoV-2 |
| title_fullStr | A ricin-based peptide BRIP from Hordeum vulgare inhibits Mpro of SARS-CoV-2 |
| title_full_unstemmed | A ricin-based peptide BRIP from Hordeum vulgare inhibits Mpro of SARS-CoV-2 |
| title_short | A ricin-based peptide BRIP from Hordeum vulgare inhibits Mpro of SARS-CoV-2 |
| title_sort | ricin based peptide brip from hordeum vulgare inhibits mpro of sars cov 2 |
| url | https://doi.org/10.1038/s41598-022-15977-y |
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