الفهرس | Only 14 pages are availabe for public view |
Abstract Abstract XIII Abstract: Aims: Structural demystifying of some viral polymerases by using sofosbuvir as a nucleotide inhibitor that has promising results in terms of its efficacy against different viral polymerases. Materials and Methods: In this study, molecular docking and dynamics simulation studies are used for the comparison of the effect of sofosbuvir (a clinically approved drug) on the treatment of different viral protein RNA-dependent RNA polymerase (RdRp). This drug was docked onto the three-dimensional structure of the nsp12 protein of SARS-CoV-2 (COVID-19) and MERS-CoV (Middle East Respiratory Syndrome), which controls the polymerization process and considered as one of the primary therapeutic targets for human coronaviruses, and docked also onto the three-dimensional structure of the NS5 protein of ZIKV, which controls the polymerization process and considered as one of the primary therapeutic targets for ZIKV. Sofosbuvir is a drug that is currently used for HCV treatment; therefore, HCV RdRp is used as a positive control target. The dynamics of the protein are simulated for 100 ns, while the binding is tested during different dynamics states of the MERS-CoV RdRp, SARSCoV- 2 RdRp and ZIKV RdRp. Key findings: The interaction of SARS-CoV- 2, MERS-CoV and ZIKV RdRps as a target with the active form of sofosbuvir as a ligand demonstrates the effectiveness of binding. One of the FDAapproved antiviral drugs such as sofosbuvir can help us in this mission, aiming to limit the danger of these viruses. Keywords: SARS-CoV-2 (COVID-19); MERS-COV; ZIKV; RdRp; Sofosbuvir; Docking; Molecular Dynamics Simulation; Drug repurposing. |