Transmembrane protease serine 2 (TMPRSS2), associated with t...

created [InstanceEdit:9694660] Cook, Justin, 2020-07-07
dbId 9694679
displayName Transmembrane protease serine 2 (TMPRSS2), associated with t...
literatureReference
modified [InstanceEdit:9769558] Stephan, Ralf, 2022-03-20
schemaClass Summation
text Transmembrane protease serine 2 (TMPRSS2), associated with the plasma membrane of the host cell, mediates the hydrolytic cleavage of SARS-CoV-2 Spike (S) protein component of the viral membrane-associate S3:M:E:encapsidated SARS coronavirus genomic RNA: 7a:O-glycosyl 3a tetramer complex associated with ACE2 (Xia et al, 2020; Bestle et al, 2020; Koch et al, 2021).

Neuropilin-1 (NRP1) is a receptor expressed in a broad range of cells from human organ systems including respiratory, urinary, digestive, reproductive, and immune systems. Specific cell lines from these organs are susceptible to SARS-CoV-2 infection. From these A549 (lung) and HRC45 (kidney) cells had a robust SARS?CoV?2 pseudovirus infection but weak levels of ACE2, and both expressed strong levels of NRP1 (Zhang et al, 2021). High levels of NRP1 were detected in the epithelial surface layer of the human respiratory and olfactory epithelium, with ACE2 hardly detectable in these tissues. Artificial additional NRP1 expression in Caco-2 and HEK-293T cells increased SARS-CoV-2 infection markedly (Cantuti-Castelvetri et al, 2020; Zhu et al, 2021). The TMPRSS2-cleaved SARS-CoV-2 spike glycoprotein fragment S1 binds NRP1, and selective NRP1 inhibitors reduced SARS-CoV-2 entry and infectivity in Caco-2 cell culture (Daly et al, 2020). Taken together, NRP1 appears to be the entry factor on NRP1-rich cells, and a weak entry factor on cells where ACE2 is present.

Several cell lines also have relatively higher levels of Hepatitis A virus cellular receptor 1 (kidney injury molecule-1, HAVCR1, KIM1, TIM1), a membrane protein upregulated upon kidney injury. Recombinant HAVCR1 blocked infection of both SARS?CoV?2 and SARS?CoV pseudoviruses in a dose?dependent fashion in one?way ANOVA analysis albeit no significant difference was detected when the treated groups were compared with the untreated infected group (Zhang et al, 2021b). HAVCR1 binds to SARS-CoV-2 spike glycoprotein. Uptake of spike virosomes by lung and kidney epithelial cells that naturally express HAVCR1 was inhibited by anti-HAVCR1 antibodies and a HAVCR1 inhibitor (Mori et al, 2022; Yang et al, 2021).
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