The objective of this study is to identify potential targets within the SARS-CoV-2 RdRp for the discovery of novel inhibitors derived from therapeutic natural compounds sourced from aromatic and medicinal plants. In the course of this study, a library was generated containing five naturally occurring flavone derivatives (4a, 4b, 4c, 4d, and 4e) in conjunction with the standard favipiravir-RTP. The compounds underwent an in-silico methodology involving critical steps, including (a) evaluating ADME parameters and ensuring compliance with Lipinski’s rule of five, (b) conducting molecular docking analysis, and (c) performing a molecular dynamics simulation lasting 100 nanoseconds. The results suggest that the top five compounds displayed a more favorable pharmacological response compared to the standard, presenting promising outcomes without identified limitations. Consequently, two flavone derivatives (4d and 4e) were chosen due to their higher binding energies compared to the reference molecule, exhibiting binding affinities of -7.036 kcal/mol and -7.141kcal/mol, respectively. Subsequently, the stability of these leading compounds bound with SARS-CoV-2 RdRp was validated through molecular dynamics (MD) simulations, revealing a consistent trajectory (RMSD, RMSF) and favorable molecular properties in their interaction profiles. The present study has identified certain compounds sourced from aromatic and medicinal plants that demonstrate in-silico potential against SARS CoV-2 RdRp. These findings indicate their appropriateness for subsequent in vitro and in vivo evaluations as potential candidates for the treatment of COVID-19 patients.
