A possible end to the pandemic?

 By: Alejandra Pena

a-c, inhibition of entry of lentiviral PVS in 293-T-ACE2 (a), Caco-2 (b) or Calu03 (c) cells by the serine protease inhibitor, camostat (green bars), or the cathepsin inhibitor, E64-d (purple bars). All assays were performed three times and are plotted as mean +s.d. The data that is shown are representative replicate (n=3). Data was normalized to no drug control (black bars). The statistics were shown by two-way ANOVA with various comparisons. d, Replication kinetics of SARS-CoV-2 WT in HAE cells. The cells were pretreated with either control media or media containing camostat for 1 h that was then infected at MOI of 0.1. (e) Caco-2 (f) Calu-3 (g) or HAES (h). Gene expression by RT-qPCR and normalized to B-actin. Figure taken from Peacock et al. 2021. 

SARS-CoV-2 entered the human population and basically consumed humanity as we know it. Coronaviruses are able to enter cells through their spike glycoprotein. In order for SARS-CoV-2 to enter the host, it requires a cleavage of the spike glycoprotein in the S1/S2 and S2’ cleave sites in order for membrane fusion to begin. Throughout the study, there was a combination of lentiviral pseudotypes with spike cleavage sites mutations and Vero-passaged SARS-CoV-2 virus variants used in order to further understand the molecular mechanism of polybasic cleavage sites of SARS-CoV-2 and their entry into the lungs. The study shows how SARS-CoV-2 viruses that lack the S1/S2 furin cleavage site showed lower titres from infected ferrets and were not transmitted onto other animals. The study then shows that TMPRSS2 is a useful drug target and although it would not prevent infection through the endosome, the pathway is crucial in preventing the replication of this virus in the airway. This study is crucial to society as the pandemic is still happening with no end in sight. There are currently clinical trials ongoing reviewing these findings and looking for ways to prevent the replication in human airway cells as well as proving that the furin cleavage site is a determinant of SARS-CoV-2 transmission.

Reference:

Peacock, T. P., Goldhill, D. H., Zhou, J. et al. 2021. The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nature Microbiology. 6, 899-909.

https://www.nature.com/articles/s41564-021-00908-w#citeas