Figure 3.

LF and LFC can interfere with SARS-CoV-2 infection through various mechanisms. SARS-CoV-2 enters cells via two different routes: (i) via the cell surface, mediated by binding to HSPGs and ACE2 with S protein processing by the cell surface serine protease TMPRSS2, which is required for membrane fusion and subsequent infection, or (ii) via endosomes, in which HSPGs, ACE2, and the endosomal cysteine protease CTSL play a role. LF has been shown to interfere with both pathways, due to binding to HSPGs (1) or directly to the S protein (3), and due to inhibition of CTSL that cleaves the S protein to release the virus from the endosome (4). Furthermore, LF has been found to inhibit viral replication by directly targeting the viral RNA-dependent RNA polymerase (RdRP, 5). Lastly, LF can boost the antiviral response through enhancing type I IFNs (6). So far, LFC has been shown to inhibit viral entry by inhibition of the protease TMPRSS2 (2).