Microbial pigments as potential anti-rift valley fever virus drugs

Abstract Rift valley fever virus (RVFV) is among the WHO list of priority diseases, yet no effective vaccine or treatment is currently available. Microbial pigments (MPs) represent a promising small-molecules library which can be exploited for the drug discovery of anti-RVFV compound. In this study, thirteen MPs were in silico screened to identify candidates with acceptable drug-likeness and possible ability to cross the blood brain barrier. Next, the binding interaction of the filtered molecules were compared against key RVFV proteins for the selection of the optimum inhibitor. Molecular dynamics simulations were performed (200 ns) to further evaluate the interactions. The selected candidate (pyocyanin; PCN) was produced, purified and analytically characterized in-house. Finally, the antiviral potential of PCN was tested in vitro against RVFV using the tissue culture infection dose 50% (TCID 50 ) method. In silico screening studies revealed that prodigiosin and PCN exhibit ideal drug-likeness properties. PCN exerted a promising in silico interaction with the key RVFV proteins as revealed by the molecular docking and dynamic studies. Results showed that PCN may be effectively produced and purified from bacterial cultures. Its cell-safe concentration (0.49 μg/mL) demonstrated a promising 2.89 log 10 reduction in TCID 50 when incubated with RVFV infected cells. A lower effect was observed (2.00 log 10 reduction) in cells treated with PCN prior to RVFV infection. These results suggest that PCN may represent a potential effective low-cost molecule to combat RVFV.