Aspergillus fumigatus secretes a protease(s) that displays in silico binding affinity towards the SARS-CoV-2 spike protein and mediates SARS-CoV-2 pseudovirion entry into HEK-293T cells

• Published in: Virology journal Vol. 21; no. 1; p. 58
• Main Authors: Mjokane, Nozethu, Akintemi, Eric O., Sabiu, Saheed, Gcilitshana, Onele M. N., Albertyn, Jacobus, Pohl, Carolina H., Sebolai, Olihile M.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 06.03.2024; BioMed Central Ltd; BMC
• Subjects: A. Fumigatus alkaline protease 1; Amino acids; Analysis; Aspergillosis; Aspergillus (A) fumigatus; Aspergillus fumigatus; Biomedical and Life Sciences; Biomedicine; Case studies; Cell culture; Communicable diseases; computer simulation; Coronaviruses; Coronaviruses: emerging and re-emerging pathogens in humans and animals; COVID-19; COVID-19 infection; Culture media; Enzymatic activity; enzyme activity; Fungal infections; Fungi; Glycoproteins; Haddock; Health aspects; HEK-293T cells; HEK293 Cells; Humans; Infectious diseases; Ligands; Medical research; Medicine, Experimental; Molecular Docking Simulation; Peptide Hydrolases; Peptides; Pharmaceutical industry; Proteases; Protein binding; proteinases; Proteins; Proteolysis; Reagents; SARS-CoV-2; SARS-CoV-2 spike protein; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; Spike protein; Supernatant; T cells; Virology; Virulence; United States; South Africa; United States > US; Germany; Haddock; HEK-293T cells; SARS-CoV-2 spike protein; Transduction; alkaline protease 1; Supernatant; A. Fumigatus alkaline protease 1; Aspergillus (A) fumigatus
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/s12985-024-02331-z

Background The novel coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Data from the COVID-19 clinical control case studies showed that this disease could also manifest in patients with underlying microbial infections such as aspergillosis. The current study aimed to determine if the Aspergillus ( A. ) fumigatus culture media (i.e., supernatant) possessed protease activity that was sufficient to activate the SARS-CoV-2 spike protein. Methods The supernatant was first analysed for protease activity. Thereafter, it was assessed to determine if it possessed proteolytic activity to cleave a fluorogenic mimetic peptide of the SARS-CoV-2 spike protein that contained the S1/S2 site and a full-length spike protein contained in a SARS-CoV-2 pseudovirion. To complement this, a computer-based tool, HADDOCK, was used to predict if A. fumigatus alkaline protease 1 could bind to the SARS-CoV-2 spike protein. Results We show that the supernatant possessed proteolytic activity, and analyses of the molecular docking parameters revealed that A. fumigatus alkaline protease 1 could bind to the spike protein. To confirm the in silico data, it was imperative to provide experimental evidence for enzymatic activity. Here, it was noted that the A. fumigatus supernatant cleaved the mimetic peptide as well as transduced the HEK-293T cells with SARS-CoV-2 pseudovirions. Conclusion These results suggest that A. fumigatus secretes a protease(s) that activates the SARS-CoV-2 spike protein. Importantly, should these two infectious agents co-occur, there is the potential for A. fumigatus to activate the SARS-CoV-2 spike protein, thus aggravating COVID-19 development.