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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 250µg/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.

Occurrence and intensity of systemic invasive fungal infections have significantly risen in recent decades with large amount of mortality and morbidity rates at global level. Treatment therapy lies on the current antifungal interventions and are often limited due to the emergence of resistance to antifungal agents. Chemosensitization of fungal strains to the conventional antimycotic drugs are of growing concern. Current antifungal drugs often have been reported with poor activity and side effects to the host and have a few number of targets to manifest their efficacy on the pathogens. Indiscriminately, the aforementioned issues have been easily resolved by the development of new intervention strategies. One such approach is to employ combinational therapy that has exhibited a great level of inhibitions than that of a single compound. Chemosensitization of pathogenic mycoses to commercial antifungal drugs could be drastically enhanced by co-application of chemosensitizers along with the conventional drugs. Chemosensitizers could address the resistance mechanisms evolved in the pathogenic fungi and targeting the system to make the organism susceptible to commercially and clinically proven antifungal drugs. However, this strategy has not been overreached to the greater level, but it needs much attention to fight against not only with the pathogen but combat the resistance mechanisms of pathogens to drugs. Natural compounds including plant compounds and microbial proteins act as potential chemosensitizers to break the resistance in mycoses. Aspergillus giganteus, a filamentous fungus, is known to produce a cysteine rich extracellular protein called as antifungal protein (AFP). AFP has shown enhanced efficacy against several filamentous and non-filamentous fungal pathogens. On the basis of the reported studies on its targeted potential against pathogenic mycoses, AFP would be fabricated as a good chemosensitizer to augment the fungicidal efficacy of commercial antimycotic drugs. This paper reviews on breakthrough in the discovery of antifungal drugs along with the resistance patterns of mycoses to commercial drugs followed by the current intervention strategies applied to augment the fungicidal potential of drugs.

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Aspergillosis is a dreadful fungal infection and are more predominant in clinical fields. Due to the limitation of antifungal drugs, there is an emergence to develop efficient antifungal compounds from natural sources. Hence, the present study deals with the validation of active compounds from Aspergillus giganteus against aspergillosis causing Aspergillus fumigatus. The most prominent antifungal proteins in Aspergillus giganteus are sarcin, thionin and chitinase. Initially, the bioavailability and toxicological properties of sarcin, thionin, chitinase and their derivatives were screened. The molecular interaction of the screened antifungal proteins against the target proteins (UDP-N-acetylglucosamine pyrophosphorylase, N-myristoyl transferase and Chitinase) of Aspergillus fumigatus was performed using Schrodinger module. The antagonistic potential of antifungal compounds on the pathogen was confirmed by SEM. The integrity of Aspergillus fumigatus cell membrane and nuclear membrane treated with antifungal compounds were analysed by determining the release of cellular materials. Further, the GC-MS profiling of volatile bioactive compounds were analysed. The results have proved the efficiency of selected compounds for their pharmacokinetic properties. Molecular interactions of selected compounds from Aspergillus giganteus with the virulence proteins of Aspergillus fumigatus have exhibited a good glide score and their druggable nature. The SEM analysis have envisaged the shrunken and damaged spores of A. fumigatus treated with antifungal compounds. The effective concentration of antifungal compounds (AFCs) was found to be 250 µg/ml (p<0.0001). The GC-MS profiling has revealed the volatile bioactive metabolites present in Aspergillus giganteus. Conclusively, the selected antagonists from Aspergillus giganteus can be a good drug candidate to treat aspergillosis.