evidence: Measured influenza activation pH values across all subtypes and species range from ∼5.0 to 6.0, trending higher in highly pathogenic H5N1 and H7N9 strains whereas seasonal human strains are more acid-stable (pH of fusion 5.0 to 5.6). Similar to IAV, SARS-CoV-2 can use mutually exclusive routes to penetrate cells: one fast pH-independent TMPRSS2-mediated plasma route, and one pH-dependent slow clathrin-mediated endocytosis via cathepsin L. The clathrin-mediated endocytosis through cathepsin L occurs only in cells devoid of TMPRSS2. Unlike TMPRSS2, which is active at the cell surface regardless of pH conditions, cathepsin L requires a low-pH environment typical of endolysosomes. Although several studies support the view that TMPRSS2-dependent early entry route is more efficient and results in a more productive infection than the cathepsin L-activated mechanisms for some SARS-coronavirus strains, recent studies indicate that Omicron SARS-CoV-2 variants favor the low-pH endosomal entry route. For fusion activity in SARS-coronavirus, cathepsin Ls have been shown to require reduced pH of at least 6.0 or lower. Although research has verified that the envelope E-protein serves as an ion channel when pH levels decrease, there have been certain inconsistencies observed between various studies and tests. [...] Citation: Aganovic A (2023) pH-dependent endocytosis mechanisms for influenza A and SARS-coronavirus. Front. Microbiol. 14:1190463. doi: 10.3389/fmicb.2023.1190463