Fig. 1

SARS-CoV-2 Viral Entry Mechanisms and Machinery. (a) SARS-CoV-2 is a lipid membrane, enveloped, plus-sense ( +) single strand (ss) RNA betacoronavirus that must undergo host lipid membrane fusion in order to gain entry into the host cell. Potential inhibitors for subsequent steps of this process are depicted. Enveloped viruses are capable of entering the host cell via (1) direct, neutral pH, plasma membrane fusion or via (2) endocytosis, where membrane fusion would rely on pH-dependent proteases and optimal intra-endosomal conditions [144, 241]. (b) Structural diagrams of key enzymes involved in viral-cellular entry. (c) Structural diagram of a spike protein (S) depicting the location of S1 and S2 subunits, following S protein cleavage, and the altered conformational states (closed and open). To initiate the entry process, S protein must undergo a conformational change from a closed to open state, which exposes the receptor binding domain (RBD) on S, allowing it to bind to angiotensin converting enzyme 2 (ACE2) on the host cell [40]. Altered S structure bound to ACE2 and S cleaved products are also shown. PDB codes for structures are referenced in Additional file 1: Table 5. Figure was created with BioRender.com