Targeting mucormycosis polyprotein (RVT_1 region) through antifungal phytochemicals: An in-silico perspective

Abstract

Mucormycosis has become a global issue due to its potential to infect and destroy organs, as well as its high fatality rate. Co-infecting with Covid 19 or when infecting after Covid 19, it becomes more lethal. Several antifungal medicines have been utilized to treat this illness, but they come with a slew of dangerous side effects. Hence, using various computational tools; the current study was attempted to determine several antifungal plant metabolites that can act as inhibitory agents of Rhizopus oryzae, which is responsible for 70% of mucormycosis cases. In total, 56 antifungal plant metabolites were evaluated against Rhizopus oryzae polyprotein (RVT_1 region). Four metabolites, i.e., emetine, jatrorrhizine, isoboldine, and 6-a-hydroxymedicarpin showed maximum binding affinity with the targeted polyprotein (RVT_1 region) according to the lowest global binding energy and binding energy. The fungal protein's critical binding sites and drug surface hotspots were uncovered. The best candidates were gone through an ADME (absorption, distribution, metabolism, and excretion) analysis to observe their drug profiles. According to the findings, none have any side effects that could interfere with their drug likeness efficiency as well as no significant toxic effects and allergenicity were found. The majority of the target classes for proposed drug candidates were enzyme groups (e.g., oxidoreductase, family a g protein-coupled receptor, enzyme, protease). Furthermore, emetine and jatrorrhizine have been proposed to have inhibitory potency against covid 19 in several studies. Hence, we strongly propose additional in vivo trials in order to experimentally validate our findings, based on the optimistic results.

Keywords

• Mucormycosis
• Black fungus
• Rhizopus oryzae
• Plant metabolites
• Molecular docking
• ADME