Targeted Action and Molecular Interactions of Sarcin and Thionin With Aspergillosis Causing <em>Aspergillus fumigatus</em>

Abstract

Fungal infections are more predominant in agricultural and clinical fields. Aspergillosis caused by Aspergillus fumigatus leads to respiratory failure in patients along with various illnesses. Due to the limitation of antifungal therapy and antifungal drugs, there is an emergence to develop efficient antifungal compounds from natural sources to cure and prevent fungal infections. The present study deals with the investigation of the mechanism of active compounds from our candidate agonist Aspergillus giganteus for aspergillosis. The integrity of treated Aspergillus fumigatus cell membrane and nuclear membrane was analyzed by determining the release of cellular materials. The antagonistic potential of antifungal compounds on the pathogen was confirmed by SEM analysis. The effective concentration of antifungal compounds (AFCs) was found to be 250&amp;micro;g/ml. The GC-MS profiling has revealed the bioactive metabolites responsible for the antagonistic nature of Aspergillus giganteus. The bioavailability and toxicological properties of pathogenesis related proteins have proved the efficiency of pharmacokinetic properties of selected compounds. Interaction of sarcin, thionin, chitinase and its derivatives from Aspergillus giganteus with the virulence proteins of UDP-N-acetylglucosamine pyrophosphorylase, N-myristoyl transferase and Chitinase have proved the druggable nature of the antifungal compounds.

Fungal Infections as an Uprising Threat to Human Health: Chemosensitization of Fungal Pathogens With AFP From Aspergillus giganteus

“…Earlier studies in our laboratory have proved the efficacy of AFP protein from Aspergillus giganteus on various human pathogens, including Aspergillus fumigatus , Aspergillus flavus , Cryptococcus neoformans , and Candida albicans ( Krishnamurthy et al., 2020 ; Ramya and Kavitha, 2021 ; Ravindhiran et al., 2021 ). Not only a human pathogen but also a phytopathogen has also been greatly governed by AFP.…”

“…Further, deep exploration into antifungal protein might provide a possible breakdown of resistance mechanism counteracted by pathogenic fungi, ultimately augmenting the strong antimycotic activity. The antifungal protein AFP is a secretory protein from a filamentous fungi Aspergillus giganteus , which are small, basic, and cysteine-rich proteins that endeavor the future antimycotic strategies due to their specific inhibitory potential on several filamentous and non-filamentous fungal pathogens ( Krishnamurthy et al., 2020 ; Ravindhiran et al., 2021 ). β-barrel topology in AFP is composed of five antiparallel β-strand, could be stabilized by four disulfide bridges, and contributes to the extreme resistance to heat and protease degradation.…”

“…In Cryptococcus neoformans , the target proteins are Farnesyl transferase (3SFX), Ionisine 5′-monophosphate dehydrogenase (4AF0), Ribokinase (6CW5), Serine/Threonine-protein phosphate 2B catalytic subunit A1 (6TZ8), Choline kinase (6WHP), Candida albicans Dihydrofolate reductase (1AI9), Myristoyl-CoA: protein N-Myristoyl transferases (1IYL), Secreted aspartyl proteases (1ZAP), and Lanosterol 14-α demethylase (5V5Z) are the potential virulence proteins responsible for the pathogenesis in the host. In silico prediction by molecular docking studies have proved that the antifungal proteins from Aspergillus giganteus and their derivatives has good interaction with the virulence proteins of Aspergillus fumigatus , Candida albicans , and Cryptococcus neoformans ( Ravindhiran et al., 2021 ). Mechanism of action of afp on both plant and human fungal pathogens is depicted in Figure 4 .…”