Cryptococcal Protease(s) and the Activation of SARS-CoV-2 Spike (S) Protein

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 3; p. 437
• Main Authors: Mjokane, Nozethu, Maliehe, Maphori, Folorunso, Olufemi S., Ogundeji, Adepemi O., Gcilitshana, Onele M. N., Albertyn, Jacobus, Pohl, Carolina H., Sebolai, Olihile M.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.01.2022; MDPI
• Subjects: Amino Acid Sequence; Amino acids; Aspartic Acid Proteases - genetics; Aspartic Acid Proteases - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Binding Sites; Coronaviruses; COVID-19; COVID-19 - epidemiology; COVID-19 - prevention & control; COVID-19 - virology; cryptococcal infection; Cryptococcus; Cryptococcus neoformans; Cryptococcus neoformans - enzymology; Cryptococcus neoformans - genetics; Efficiency; Experiments; Fluorescent Dyes - chemistry; fluorogenic peptide; Furin; Furin - genetics; Furin - metabolism; Glucose; Humans; Mutation; Pandemics; Peptides; Peptides - chemistry; Peptides - metabolism; Pneumonia; protease; Proteinase; Proteins; Proteolysis; SARS-CoV-2 - metabolism; SARS-CoV-2 - physiology; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - metabolism; South Africa; United States > US; China; Germany; protease; SARS-CoV-2; Cryptococcus neoformans; spike (S) protein; Cryptococcus; S1/S2 cleavage site; fluorogenic peptide; furin; cryptococcal infection; proteolytic cleavage
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11030437

In this contribution, we report on the possibility that cryptococcal protease(s) could activate the SARS-CoV-2 spike (S) protein. The S protein is documented to have a unique four-amino-acid sequence (underlined, SPRRAR↓S) at the interface between the S1 and S2 sites, that serves as a cleavage site for the human protease, furin. We compared the biochemical efficiency of cryptococcal protease(s) and furin to mediate the proteolytic cleavage of the S1/S2 site in a fluorogenic peptide. We show that cryptococcal protease(s) processes this site in a manner comparable to the efficiency of furin (p > 0.581). We conclude the paper by discussing the impact of these findings in the context of a SARS-CoV-2 disease manifesting while there is an underlying cryptococcal infection.