Title : Activation of SARS-CoV-2 spike protein by a fungal protease(s)
Abstract:
SARS-CoV-2 is the causative agent of the novel corona virus disease of 2019 (COVID-19). It first emerged in the city of Wuhan, China in December 2019 and has resulted in millions of infections and deaths worldwide. To invade a cell, this enveloped virus targets cells that display ACE-2 receptors and relies on host serine protease(s) such as furin for the initial priming of the spike protein. Importantly, COVID-19 may also manifest in persons with underlying microbial infections. Some of these microbes like Cryptococcus neoformans secrete microbial protease(s) to breach the epithelial barriers for purposes of dissemination. It is in this context that microbial protease(s) may also activate the spike protein of SARS-CoV-2.
To investigate the latter, a fluorogenic peptide mimetic of the spike protein with a furin cleavage site was used. Thereafter, the biochemical efficiency of cryptococcal protease(s) to mediate cleavage of a potential furin site (underlined, SPRRAR↓S) at the interface between the S1 and S2 subunit was compared to that of a recombinant furin.
We observed that cryptococcal protease(s) processes this site in a manner comparable to the efficiency of furin (p > 0.581). In general, this preliminary work suggests cryptococcal protease(s) have the potential to activate S protein of SARS-CoV-2 leading to host invasion.
Audience Take Away:
- The audience will understand the impact of coexistence of Cryptococcus neoformans and SARS-CoV-2 in a host.
- Could use some of the experimental procedures in their related projects.
- Faculty could use to expand their research or teaching
- Yes, the potential manifestation of COVID-19 in the context of an underlying cryptococcal infection could result in the synergistic activation of SARS-CoV-2 spike protein by cryptococcal proteases.
- This would help to establish sufficient merit to clear any underlying microbial infection.
- It would improve the vaccine response.
