Rift valley fever virus (RVFV) is the causative agent of a viral zoonosis that causes a significant clinical burden in domestic and wild ruminants.Major outbreaks of the virus occur in livestock, and contaminated animal products or arthropod vectors can transmit the virus to humans.The viral RNA-dependent RNA polymerase (RdRp; L protein) of the RVFV is responsible for viral replication and is thus an appealing drug target because no Contribuições da estratégia de ensino estudo de caso para o desenvolvimento de habilidades didáticas em licenciandos de Química effective and specific vaccine against this virus is available.The current study reported the structural elucidation of the RVFV-L protein by in-depth homology modeling since no crystal structure is available yet.
The inhibitory binding modes of known potent L protein inhibitors were analyzed.Based on the results, further molecular docking-based virtual screening of Selleckchem Nucleoside Analogue Library (156 compounds) was performed to find potential new inhibitors against the RVFV L protein.ADME (Absorption, Distribution, Metabolism, and Excretion) and toxicity analysis of these compounds was also performed.Besides, the binding mechanism and stability of identified compounds were confirmed by a 50 ns molecular dynamic (MD) simulation followed by MM/PBSA binding free energy calculations.
Homology modeling determined a stable multi-domain structure of L protein.An analysis of known Machine Learning-Based Analysis of the Association Between Online Texts and Stock Price Movements L protein inhibitors, including Monensin, Mycophenolic acid, and Ribavirin, provide insights into the binding mechanism and reveals key residues of the L protein binding pocket.The screening results revealed that the top three compounds, A-317491, Khasianine, and VER155008, exhibited a high affinity at the L protein binding pocket.ADME analysis revealed good pharmacodynamics and pharmacokinetic profiles of these compounds.
Furthermore, MD simulation and binding free energy analysis endorsed the binding stability of potential compounds with L protein.In a nutshell, the present study determined potential compounds that may aid in the rational design of novel inhibitors of the RVFV L protein as anti-RVFV drugs.