Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

Abstract

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Virological characteristics of SARS-CoV-2 BA.2 variant

“…We then analysed the binding affinity of BA.2 S receptor binding domain (RBD) to ACE2 by an yeast surface display assay 16,22,24 . Although the binding affinity of BA.1 S RBD to ACE2 is controversial 11,[15][16][17]25,26 , our yeast surface display showed that the binding affinity of the RBD of BA.1 and BA.2 is comparable (Extended Data Fig. 6b).…”

“…We have recently revealed that BA.1 poorly utilizes TMPRSS2 for the infection 11 . To analyse the TMPRSS2 usage by BA.2 S, we performed cell-based fusion assay using 293-ACE2 cells with or without TMPRSS2 expression.…”

“…Notably, BA.2 has initiated outcompeting BA.1 3 , suggesting that BA.2 is more transmissible than BA. 1. In a few months since the emergence of BA.1, we and others revealed the virological characteristics of BA.1 [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . For instance, BA.1 is highly resistant to the vaccine-induced humoral immunity and antiviral drugs [4][5][6][7][8][9][10][11][16][17][18][19] .…”

“…1. In a few months since the emergence of BA.1, we and others revealed the virological characteristics of BA.1 [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . For instance, BA.1 is highly resistant to the vaccine-induced humoral immunity and antiviral drugs [4][5][6][7][8][9][10][11][16][17][18][19] . Also, the spike (S) protein of BA.1 is less efficiently cleaved by furin and less fusogenic than those of Delta and an ancestral SARS-CoV-2 belonging to the B.1.1 lineage 11,12 .…”

SARS-CoV-2 Permissive Glioblastoma Cell Line for High Throughput Antiviral Screening

“…The copyright holder for this this version posted February 14, 2022. ; https://doi.org /10.1101/2022.02.13.480238 doi: bioRxiv preprint prime the S protein into its fusogenic state (10,11). Notably, reports on current circulating SARS-CoV-2 variants of concern demonstrate that Omicron infection is not enhanced by TMPRSS2 but is largely mediated via the endocytic pathway (12,13).…”