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

Nozethu Mjokane,Jacobus Albertyn,Onele M N Gcilitshana,Maphori Maliehe,Adepemi O Ogundeji,Olihile M Sebolai,Carolina H Pohl,Olufemi S Folorunso

doi:10.3390/cells11030437

Abstract

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.

Highlights

Cryptococcal Protease(s) and theThe novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, the etiological agent of the coronavirus disease of 2019, COVID-19), emerged in December of 2019 in Wuhan, China [1]
Jaimes et al reported that the early characterisation of the S protein revealed a unique site, i.e., constituted by a sequence of four amino acids at the interface between the S1 and S2 subunits, that serves as a potential cleavage site for furin [1,12–15]
We showed that cryptococcal protease(s) mediated the proteolytic cleavage of the fluorogenic peptide in a manner that was comparable to the efficiency of furin (p > 0.581)

Summary

Introduction

The novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, the etiological agent of the coronavirus disease of 2019, COVID-19), emerged in December of 2019 in Wuhan, China [1]. Patients may display mild symptoms and some may experience severe complications such as acute respiratory distress syndrome (ARDS). The proteolytic cleavage of the S protein is documented to create an unstable receptor-binding domain that, in turn, leads to membrane fusion and subsequent endocytosis [9]. Several host proteases such as the trypsin-like protease (e.g., TMPRSS2), endopeptidases, including members of the cathepsin family, have been documented to catalyse the activation of the S protein [10,11]. Jaimes et al reported that the early characterisation of the S protein revealed a unique site, i.e., constituted by a sequence of four amino acids (underlined, SPRRAR↓S) at the interface between the S1 and S2 subunits, that serves as a potential cleavage site for furin [1,12–15]

Methods

Results

Discussion

Conclusion