Repurposing proteases: An in-silico analysis of the binding potential of extracellular fungal proteases with selected viral proteins

Abstract

Proteases have long been the target of many drugs, but their potential as therapeutic agents is a well-known, but under-explored area. Due to the heightened threat from new and emerging infectious agents, it is worthwhile to tap into the vast microbial protease resource to identify potential therapeutics. By docking proteases of the fungus Penicillium janthinellum NCIM 1366 with the proteins encoded by the SARS-CoV-2 virus, the enzymes that have the potential to bind with, and thereby degrade viral proteins were identified. In-silico docking analysis revealed that both fungal and commercially available proteases belonging to the A1A, M20A, S10, S8A and T1A families were able to bind the viral spike, envelope, ORF-7a and Nsp2 proteins (binding energy < −50 kJ/mol), thereby opening up the possibility of developing additional therapeutic applications for these enzymes.

Early cellular events and potential regulators of cellulase induction in Penicillium janthinellum NCIM 1366

“…From the whole genome sequence data, 13 secreted cellulases were identified based on SignalP, dBCAN and UniProt annotations (Table 1). The number of exoglucanases (4), endoglucanases (7) and BGLs (2) are comparable to that of other fungi like Trichoderma and Neurospora. Therefore, the means for achieving higher cellulase activity is by massive upregulation and secretion of the cellulase genes, particularly of the cellobiohydrolases (Fig.…”

“…Secretome profiles of induced PJ-1366 cultures. PJ-1366 encodes 11,828 proteins, of which 1007 have signal peptides 7 . Of the extracellular proteins, 216 proteins were described as carbohydrate-active enzymes (CAZymes), of which 165 were Glycoside Hydrolases (GH), that include the cellulases and hemicellulases 8 .…”

Enzyme Therapy: Current Challenges and Future Perspectives

“…Approaches using a modified formulation of the catalase, an ubiquitous antioxidant enzyme, have proven to decrease viral load and enhance recovery when administrated intravenously or nebulized in rhesus macaques [142], attractive qualities which make it suited for human studies. Moreover, an in silico study has suggested attractive proteases as therapeutics against SARS-CoV-2 [143]. This study addressed the binding capabilities of fungal proteases, some of which are used in the food and textile industries, to several of the SARS-CoV-2 proteins.…”