SARS-CoV-2 S glycoprotein binding to multiple host receptors enables cell entry and infection

Abstract

Graphical abstract The severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) infection displays a wide array of clinical manifestations. Although some risk factors for coronavirus disease 2019 (COVID-19) severity and outcomes have been identified the underlying biologic mechanisms are still not well understood. The surface SARS-CoV-2 proteins are heavily glycosylated enabling host cell interaction and viral entry. Angiotensin-converting enzyme 2 (ACE2) has been identified to be the main host cell receptor enabling SARS-CoV-2 cell entry after interaction with its S glycoprotein. However, recent studies report SARS-CoV-2 S glycoprotein interaction with other cell receptors, mainly C-type lectins which recognize specific glycan epitopes facilitating SARS-CoV-2 entry to susceptible cells. Here, we are summarizing the main findings on SARS-CoV-2 interactions with ACE2 and other cell membrane surface receptors and soluble lectins involved in the viral cell entry modulating its infectivity and potentially playing a role in subsequent clinical manifestations of COVID-19.

Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19

“…This protein is exclusively expressed in Langerhans cells (LC)–the first dendritic cells to encounter pathogens entering the body via the mucosa or skin [ 64 ]. Langerin binds COVID-19 glycoprotein glycans; however, it does not mediate transfection of COVID-19 pseudovirions in a T-lymphocyte cell line [ 65 ], rendering its role in COVID-19 infections inconclusive [ 66 ]. Our findings showed evidence consistent with high levels of SFTPD potentially protecting against COVID-19 hospitalization.…”

Mechanism of Multi-Organ Injury in Experimental COVID-19 and Its Inhibition by a Small Molecule Peptide

“…Coronaviruses have advanced various mechanisms to identify diverse receptors for their cross- species transmission and expansion. These viruses use a variety of cellular receptors and co- receptors that allow them to infect a wide range of avian and mammalian species ( Trbojević- Akmačić et al, 2021 ; Zhang et al, 2021 ). The spike protein mainly mediates viral entry into host cells ( Huang et al, 2020 ; Trbojević-Akmačić et al, 2021 ; Zhang et al, 2021 ), although several other molecules have been suggested (e.g., C-type lectins, DC-SIGN, L-SIGN) ( Rahimi, 2020 ; Thépaut et al, 2021 ; Jackson et al, 2022 ).…”

“…These viruses use a variety of cellular receptors and co- receptors that allow them to infect a wide range of avian and mammalian species ( Trbojević- Akmačić et al, 2021 ; Zhang et al, 2021 ). The spike protein mainly mediates viral entry into host cells ( Huang et al, 2020 ; Trbojević-Akmačić et al, 2021 ; Zhang et al, 2021 ), although several other molecules have been suggested (e.g., C-type lectins, DC-SIGN, L-SIGN) ( Rahimi, 2020 ; Thépaut et al, 2021 ; Jackson et al, 2022 ). During maturation, the spike protein is cleaved into receptor binding and membrane fusion subunits (S1 and S2 subunits, respectively) ( Duan et al, 2020 ; Huang et al, 2020 ; Jackson et al, 2022 ).…”

IgG N-glycome changes during the course of severe COVID-19: An observational study

“… 4 SARS-CoV-2 entry into host cells is an essential step of viral infectivity and pathogenesis, mediated by the spike glycoprotein S interaction, predominantly with angiotensin-converting enzyme 2 (ACE2). 5 After SARS-CoV-2 binding to a cell surface receptor, receptor transmembrane protease serine 2 (TMPSRR2) cleaves SARS-CoV-2 S glycoprotein between S1 and S2 domains, enabling S1 detachment, conformational changes of S2, and fusion of viral and host cell membrane. 6 Alternatively, SARS-CoV-2 can utilize the endosomal pathway to enter the cells.…”