Abstract
Context: Rift Valley fever (RVF) is a disease caused by the RVF virus (RVFV), concentrated mostly in Africa. The virus, usually found in animals, can infect humans through contact with infected animals or mosquito vectors. No established treatment exists, as infections are typically mild and self-resolving. However, in 1% of cases, the disease progresses to a more severe form, prompting further research on effective medication. Recently, favipiravir demonstrated the ability to alleviate RVFV symptoms by hindering replication by inhibiting the RdRp protein. This insight opens the door to drug repurposing efforts, focusing on RNA polymerase inhibitors as potential treatment options for RVF. Aims: To evaluate known RdRp inhibitors for the RVFV’s RdRp protein to halt viral replication. Methods: RNA polymerase inhibitors were selected from databases and reference papers using ADME values and toxicity levels followed by structural bioinformatics analysis of four best candidates and control. Results: Molecular docking showed the four candidates having equal or higher binding affinities than the control, favipiravir, across various binding pockets. Further molecular dynamics simulation shows a stable protein-ligand interaction based on the fluctuation plot. Hydrophobic interaction and hydrogen bonds from the 2D and 3D visualization indicate ribavirin has the strongest hydrogen bond, and molnupiravir has the most amino acids contributing to hydrophobic interactions. Conclusions: ADMETox, molecular docking, molecular dynamics simulations, and bond force analysis indicate the possibility of favipiravir, molnupiravir, galidesivir, ribavirin, and tenofovir as promising candidates as inhibitors for the RVFV’s RdRp protein to halt viral replication.