Bioactive Alkaloids from Genus Aspergillus: Mechanistic Interpretation of Their Antimicrobial and Potential SARS-CoV-2 Inhibitory Activity Using Molecular Modelling

Abstract

Genus Aspergillus represents a widely spread genus of fungi that is highly popular for possessing potent medicinal potential comprising mainly antimicrobial, cytotoxic and antioxidant properties. They are highly attributed to its richness by alkaloids, terpenes, steroids and polyketons. This review aimed to comprehensively explore the diverse alkaloids isolated and identified from different species of genus Aspergillus that were found to be associated with different marine organisms regarding their chemistry and biology. Around 174 alkaloid metabolites were reported, 66 of which showed important biological activities with respect to the tested biological activities mainly comprising antiviral, antibacterial, antifungal, cytotoxic, antioxidant and antifouling activities. Besides, in silico studies on different microbial proteins comprising DNA-gyrase, topoisomerase IV, dihydrofolate reductase, transcriptional regulator TcaR (protein), and aminoglycoside nucleotidyl transferase were done for sixteen alkaloids that showed anti-infective potential for better mechanistic interpretation of their probable mode of action. The inhibitory potential of compounds vs. Angiotensin-Converting Enzyme 2 (ACE2) as an important therapeutic target combating COVID-19 infection and its complication was also examined using molecular docking. Fumigatoside E showed the best fitting within the active sites of all the examined proteins. Thus, Aspergillus species isolated from marine organisms could afford bioactive entities combating infectious diseases.

Keywords: Aspergillus; alkaloids; antimicrobial activity; molecular modelling.

Figure 1

Alkaloids isolated from Aspergillus carneus and A. flavus.

Figure 2

Alkaloids isolated from Aspergillus fumigatus.

Figure 3

Alkaloids isolated from Aspergillus fumigatus (cont’d).

Figure 4

Alkaloids isolated from Aspergillus nidulans, A. ochraceus, A. oryzae and A. puniceus.

Figure 5

Alkaloids isolated from A. sulphureus, A. sydowii, A. tamari and A. terreus.

Figure 6

Alkaloids isolated from A. versicolor.

Figure 7

Alkaloids isolated from A. westerdijkiae.

Figure 8

Alkaloids isolated from miscellaneous Aspergillus species.

Figure 9

Alkaloids isolated from miscellaneous Aspergillus species.

Figure 10

Percentages of different biological activities for the bioactive alkaloids of genus Aspergillus.

Figure 11

2D binding mode of Fumigatoside E (28) in the binding sites of DNA-gyrase (A), topoisomerase IV (B), dihydrofolate reductase (C), β-lactamase (D), transcriptional regulator TcaR (E) and aminoglycoside nucleotidyl transferase (F). Dotted green lines indicate H-bonds; dotted light green lines indicate C-H-bonds; dotted purple lines indicate π-bonds; dotted orange bonds indicate salt bridge formation.

Figure 12

2D and 3D binding mode of Fumigatoside E (28) (A) and Aspergicin (150) (B) in the binding site ACE2.