Evolution of SARS-CoV-2 entry mechanism into host cells during infection

Abstract

SARS-CoV-2 was responsible for the highly destructive pandemic that started in early 2020, with the Omicron lineage being dominant for half of the pandemic due to its higher transmission rate. However, Omicron variants appear to be less infectious and thought to enter the target cell less efficiently. Omicron’s lack of infectivity has been associated with an increased usage of the endosomal pathway for viral entry and lower dependance on TMPRSS2. In this review, we aim to provide an outlook on the available data regarding the Omicron entry mechanisms and the current lack of consensus in the topic. It remains unclear which mechanism is preferred by SARS-CoV-2 Omicron variants to infect host cells as well as Omicron’s relationship with TMPRSS2 during viral entry. We propose to conduct further mutations and variants of concern-based studies on human cell organoids and in vivo to understand SARS-CoV-2 Omicron entry pathway mechanism and access TMPRSS2 and the dependency.