Fig. 4.

SARS-CoV-2 cell entry mechanisms and subsequent intracellular trafficking. a) Role of host cell proteases in the cellular entry of SARS-CoV-2. Host cell entry of SARS-CoV can proceed via two distinct routes; in the absence of SARS-S-activating protease, the virus is internalized via the binding of SARS-S to ACE2 on the surface of host cells. Within the endosomes, the SARS-S is then cleaved and activated by cathepsin L, a pH-dependent cysteine protease. The SARS-S may also be activated by TMPRSS2 on the membrane surface of host cells when this protease is expressed along with ACE2 allowing the fusion of two membranes (i.e., host and the virus) and viral entrance. b) The role of class I transmembrane proteins expressed on the surface of SARS-CoV-2 in promoting membrane fusion. Conformational changes of these proteins before and after fusion have been shown. c) The conformation of the viral S2 protein has also been indicated in vitro (left) and in vivo (right). Abbreviations: FP, fusion peptide; HR-N, heptad repeat region N; HR-C, heptad repeat region C; IC, intracellular tail; SARS-CoV-2, severe acute respiratory syndrome coronavirus; TM, transmembrane anchor.