In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein
Despite ongoing vaccination programs against COVID-19 around the world, cases of infection are still rising with new variants. This infers that an effective antiviral drug against COVID-19 is crucial along with vaccinations to decrease cases. A potential target of such antivirals could be the membra...
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MDPI AG
2022-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/24/8957 |
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| author | Saroj Basnet Rishab Marahatha Asmita Shrestha Salyan Bhattarai Saurav Katuwal Khaga Raj Sharma Bishnu P. Marasini Salik Ram Dahal Ram Chandra Basnyat Simon G. Patching Niranjan Parajuli |
| author_facet | Saroj Basnet Rishab Marahatha Asmita Shrestha Salyan Bhattarai Saurav Katuwal Khaga Raj Sharma Bishnu P. Marasini Salik Ram Dahal Ram Chandra Basnyat Simon G. Patching Niranjan Parajuli |
| author_sort | Saroj Basnet |
| collection | DOAJ |
| description | Despite ongoing vaccination programs against COVID-19 around the world, cases of infection are still rising with new variants. This infers that an effective antiviral drug against COVID-19 is crucial along with vaccinations to decrease cases. A potential target of such antivirals could be the membrane components of the causative pathogen, SARS-CoV-2, for instance spike (S) protein. In our research, we have deployed in vitro screening of crude extracts of seven ethnomedicinal plants against the spike receptor-binding domain (S1-RBD) of SARS-CoV-2 using an enzyme-linked immunosorbent assay (ELISA). Following encouraging in vitro results for <i>Tinospora cordifolia</i>, in silico studies were conducted for the 14 reported antiviral secondary metabolites isolated from <i>T. cordifolia</i>—a species widely cultivated and used as an antiviral drug in the Himalayan country of Nepal—using Genetic Optimization for Ligand Docking (GOLD), Molecular Operating Environment (MOE), and BIOVIA Discovery Studio. The molecular docking and binding energy study revealed that cordifolioside-A had a higher binding affinity and was the most effective in binding to the competitive site of the spike protein. Molecular dynamics (MD) simulation studies using GROMACS 5.4.1 further assayed the interaction between the potent compound and binding sites of the spike protein. It revealed that cordifolioside-A demonstrated better binding affinity and stability, and resulted in a conformational change in S1-RBD, hence hindering the activities of the protein. In addition, ADMET analysis of the secondary metabolites from <i>T. cordifolia</i> revealed promising pharmacokinetic properties. Our study thus recommends that certain secondary metabolites of <i>T. cordifolia</i> are possible medicinal candidates against SARS-CoV-2. |
| first_indexed | 2024-03-09T16:02:09Z |
| format | Article |
| id | doaj.art-5043a02980384cc6af5cc17a89c7dadb |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T16:02:09Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-5043a02980384cc6af5cc17a89c7dadb2023-11-24T17:00:21ZengMDPI AGMolecules1420-30492022-12-012724895710.3390/molecules27248957In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike ProteinSaroj Basnet0Rishab Marahatha1Asmita Shrestha2Salyan Bhattarai3Saurav Katuwal4Khaga Raj Sharma5Bishnu P. Marasini6Salik Ram Dahal7Ram Chandra Basnyat8Simon G. Patching9Niranjan Parajuli10Center for Drug Design and Molecular Simulation Division, Kathmandu 44600, NepalCentral Department of Chemistry, Tribhuvan University, Kathmandu 44618, NepalCentral Department of Chemistry, Tribhuvan University, Kathmandu 44618, NepalParaza Pharma, Inc., 2525 Avenue Marie-Curie, Montreal, QC H4S 2E1, CanadaCentral Department of Chemistry, Tribhuvan University, Kathmandu 44618, NepalCentral Department of Chemistry, Tribhuvan University, Kathmandu 44618, NepalNepal Health Research Council, Ramshah Path, Kathmandu 44600, NepalDepartment of Chemistry, Oklahoma State University, Still Water, OK 74078, USACentral Department of Chemistry, Tribhuvan University, Kathmandu 44618, NepalIndependent Researcher, Leeds LS2 9JT, UKCentral Department of Chemistry, Tribhuvan University, Kathmandu 44618, NepalDespite ongoing vaccination programs against COVID-19 around the world, cases of infection are still rising with new variants. This infers that an effective antiviral drug against COVID-19 is crucial along with vaccinations to decrease cases. A potential target of such antivirals could be the membrane components of the causative pathogen, SARS-CoV-2, for instance spike (S) protein. In our research, we have deployed in vitro screening of crude extracts of seven ethnomedicinal plants against the spike receptor-binding domain (S1-RBD) of SARS-CoV-2 using an enzyme-linked immunosorbent assay (ELISA). Following encouraging in vitro results for <i>Tinospora cordifolia</i>, in silico studies were conducted for the 14 reported antiviral secondary metabolites isolated from <i>T. cordifolia</i>—a species widely cultivated and used as an antiviral drug in the Himalayan country of Nepal—using Genetic Optimization for Ligand Docking (GOLD), Molecular Operating Environment (MOE), and BIOVIA Discovery Studio. The molecular docking and binding energy study revealed that cordifolioside-A had a higher binding affinity and was the most effective in binding to the competitive site of the spike protein. Molecular dynamics (MD) simulation studies using GROMACS 5.4.1 further assayed the interaction between the potent compound and binding sites of the spike protein. It revealed that cordifolioside-A demonstrated better binding affinity and stability, and resulted in a conformational change in S1-RBD, hence hindering the activities of the protein. In addition, ADMET analysis of the secondary metabolites from <i>T. cordifolia</i> revealed promising pharmacokinetic properties. Our study thus recommends that certain secondary metabolites of <i>T. cordifolia</i> are possible medicinal candidates against SARS-CoV-2.https://www.mdpi.com/1420-3049/27/24/8957<i>Tinospora cordifolia</i>spike proteinmolecular dockingmolecular dynamics simulation |
| spellingShingle | Saroj Basnet Rishab Marahatha Asmita Shrestha Salyan Bhattarai Saurav Katuwal Khaga Raj Sharma Bishnu P. Marasini Salik Ram Dahal Ram Chandra Basnyat Simon G. Patching Niranjan Parajuli In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein Molecules <i>Tinospora cordifolia</i> spike protein molecular docking molecular dynamics simulation |
| title | In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein |
| title_full | In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein |
| title_fullStr | In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein |
| title_full_unstemmed | In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein |
| title_short | In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein |
| title_sort | in vitro and in silico studies for the identification of potent metabolites of some high altitude medicinal plants from nepal inhibiting sars cov 2 spike protein |
| topic | <i>Tinospora cordifolia</i> spike protein molecular docking molecular dynamics simulation |
| url | https://www.mdpi.com/1420-3049/27/24/8957 |
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