In this study, the authors sought to investigate the virological characteristics of Omicron variant and compared it with the Delta variant which has dominated the world since mid-2021. Omicron variant replicated more slowly than the Delta variant in transmembrane serine protease 2 (TMPRSS2)-overexpressing VeroE6 (VeroE6/TMPRSS2) cells. Notably, the Delta variant replicated well in Calu-3 cells which has robust TMPRSS2 expression, while the Omicron variant replicated poorly in this cell line. To confirm the difference in entry pathway between the Omicron and Delta variants, the authors assessed the antiviral effect of bafilomycin A1, chloroquine (inhibiting endocytic pathway) and camostat (inhibiting TMPRSS2 pathway). Camostat potently inhibit the Delta variant but not the Omicron variant, while bafilomycin A1 and chloroquine could inhibit both Omicron and Delta variants. Moreover, Omicron variant also showed weaker cell-cell fusion activity when compared with Delta variant in VeroE6/TMPRSS2 cells. Collectively, their results suggest that Omicron variant infection is not enhanced by TMPRSS2 but is largely mediated via the endocytic pathway. The difference in entry pathway between Omicron and Delta variant may have implication on the clinical manifestations or disease severity.
Zhao H, Lu L, Peng Z, Chen LL, Meng X, Zhang C, Ip JD, Chan WM, Chu AW, Chan KH, Jin DY, Chen H, Yuen KY, To KK. SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with delta variant in TMPRSS2-expressed cells. Emerg Microbes Infect. 2021 Dec 24:1-18.
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