Molecular Docking Studies of Phytochemicals Against RNA-dependent RNA Polymerase of Mucormycosis

Abstract

Background: Mucormycosis, also referred to as black fungus, is a fatal Angio invasive fungal infection caused by a colony of molds known as mucoromycetes. <i>Rhizopus oryzae</i> is a major fungus that is responsible for almost 70% of the total mucormycosis cases. RNA-dependent RNA polymerase (RdRp), is a crucial enzyme in the RNA polymerization mechanism in various species, including <i>R. oryzae</i>. In the past, inhibiting this enzyme has been found to be a viable technique for eradicating viral infections. This research aims to identify efficacious bioactive compounds by screening antifungal phytochemicals against the RNA-dependent RNA polymerase (RdRp) protein using a bioinformatic approach to develop an effective treatment for mucormycosis. Methods: The antifungal activity of various phytochemicals against the RNA-dependent RNA polymerase (RdRp) protein was studied using in silico screening. Using the Swiss ADME online server, phytochemicals with proven antifungal properties were assessed to predict the pharmacokinetic aspects and drug-like nature. Furthermore, Molecular docking and toxicity analysis was performed using PyRx and ProTox webserver tools respectively. Results: Among the 1000 antifungal phytochemicals chosen to be evaluated against RdRp, 209 molecules were shortlisted for further studies. The binding affinity scores revealed that Dregamine (-11.1 kcal/mol), Alantolactone (-9.5), Isoalantolactone (-9.5) and Solasodine (-9.5) exhibited the lowest energy value, indicating a strong binding affinity against RdRp. Conclusion: Eventually, the most promising analogues can be further synthesized and evaluated to confirm their actual antifungal activity, allowing them to be used as potent bioactive compounds in the treatment of mucormycosis.