Diverse bioactive secondary metabolites from Aspergillus terreus: antimicrobial, anticancer, and anti-SARS-CoV-2 activity studies.

Owing to its high interest as prolific source of diverse bioactive compounds referred in our previous research work, we have scaled-up the fermentation of the marine Aspergillus terreus LGO13 on a liquid culture medium to isolate and identify the very minor/further promising bioactive secondary metabolites and to study their antibacterial, cytotoxic, and antiviral properties. Twenty-three known bioactive metabolites, including the recently discovered microbial natural product N-benzoyl-tryptophan (1), were obtained herein. Their structures were determined using HR-ESI-MS 1D/2D NMR spectroscopy and data from the literature. The biological properties of the microbial extract and the resulting compounds were examined using a set of microorganisms, cervix carcinoma KB-3-1, nonsmall cell lung cancer (NSCLC) A549, and coronavirus (SARS-CoV-2), respectively. Molecular docking (MD) simulations were used to investigate the potential targets of the separated metabolites as anti-SARS-CoV-2 drugs. According to the current study, a viral protein that may be the target of anticovid drugs is a papain-like protease (PLpro), and chaetominine (2) appears to be a viable choice against this protein. We evaluated the antiviral efficacy of chaetominine (2), fumitremorgin C (6), and azaspirofuran A (9) against SARS-CoV-2 based on MD data. Chaetominine (2) and azaspirofuran A (9) displayed intermediate selectivity indices (SI = 6.6 and 3.2, respectively), while fumitremorgin C (6) displayed a high selectivity index (SI = 19.77). These findings show that fumitremorgin C has promising antiviral action against SARS-CoV-2.