| Autor: |
Basnet S; Center for Drug Design and Molecular Simulation Division, Kathmandu 44600, Nepal., Marahatha R; Central Department of Chemistry, Tribhuvan University, Kathmandu 44618, Nepal.; Department of Chemistry, Oklahoma State University, Still Water, OK 74078, USA., Shrestha A; Central Department of Chemistry, Tribhuvan University, Kathmandu 44618, Nepal., Bhattarai S; Paraza Pharma, Inc., 2525 Avenue Marie-Curie, Montreal, QC H4S 2E1, Canada., Katuwal S; Central Department of Chemistry, Tribhuvan University, Kathmandu 44618, Nepal., Sharma KR; Central Department of Chemistry, Tribhuvan University, Kathmandu 44618, Nepal., Marasini BP; Nepal Health Research Council, Ramshah Path, Kathmandu 44600, Nepal., Dahal SR; Department of Chemistry, Oklahoma State University, Still Water, OK 74078, USA.; Oakridge National Laboratory, Bethel Valley Rd, Oak Ridge, TN 37830, USA., Basnyat RC; Central Department of Chemistry, Tribhuvan University, Kathmandu 44618, Nepal., Patching SG; Independent Researcher, Leeds LS2 9JT, UK., Parajuli N; Central Department of Chemistry, Tribhuvan University, Kathmandu 44618, Nepal. |
| Abstrakt: |
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 Tinospora cordifolia , in silico studies were conducted for the 14 reported antiviral secondary metabolites isolated from T. cordifolia -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 T. cordifolia revealed promising pharmacokinetic properties. Our study thus recommends that certain secondary metabolites of T. cordifolia are possible medicinal candidates against SARS-CoV-2. |
