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Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells?

Institute for Health and Sport, Victoria University, Melbourne 3030, Australia
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Authors to whom correspondence should be addressed.
These authors contributed equally.
Int. J. Mol. Sci. 2021, 22(3), 992; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22030992
Received: 26 October 2020 / Revised: 18 January 2021 / Accepted: 18 January 2021 / Published: 20 January 2021
(This article belongs to the Special Issue Molecular Research in Emerging Viruses 2020)
The occurrence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVD-19), represents a catastrophic threat to global health. Protruding from the viral surface is a densely glycosylated spike (S) protein, which engages angiotensin-converting enzyme 2 (ACE2) to mediate host cell entry. However, studies have reported viral susceptibility in intra- and extrapulmonary immune and non-immune cells lacking ACE2, suggesting that the S protein may exploit additional receptors for infection. Studies have demonstrated interactions between S protein and innate immune system, including C-lectin type receptors (CLR), toll-like receptors (TLR) and neuropilin-1 (NRP1), and the non-immune receptor glucose regulated protein 78 (GRP78). Recognition of carbohydrate moieties clustered on the surface of the S protein may drive receptor-dependent internalization, accentuate severe immunopathological inflammation, and allow for systemic spread of infection, independent of ACE2. Furthermore, targeting TLRs, CLRs, and other receptors (Ezrin and dipeptidyl peptidase-4) that do not directly engage SARS-CoV-2 S protein, but may contribute to augmented anti-viral immunity and viral clearance, may represent therapeutic targets against COVID-19. View Full-Text
Keywords: angiotensin-converting enzyme 2; ACE2; COVID-19; c-lectin type receptor; glucose-regulated protein 78; SARS-CoV-2; spike protein; toll-like receptor; N-glycans; glycosylation; mannose receptor angiotensin-converting enzyme 2; ACE2; COVID-19; c-lectin type receptor; glucose-regulated protein 78; SARS-CoV-2; spike protein; toll-like receptor; N-glycans; glycosylation; mannose receptor
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MDPI and ACS Style

Gadanec, L.K.; McSweeney, K.R.; Qaradakhi, T.; Ali, B.; Zulli, A.; Apostolopoulos, V. Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells? Int. J. Mol. Sci. 2021, 22, 992. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22030992

AMA Style

Gadanec LK, McSweeney KR, Qaradakhi T, Ali B, Zulli A, Apostolopoulos V. Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells? International Journal of Molecular Sciences. 2021; 22(3):992. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22030992

Chicago/Turabian Style

Gadanec, Laura K., Kristen R. McSweeney, Tawar Qaradakhi, Benazir Ali, Anthony Zulli, and Vasso Apostolopoulos. 2021. "Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells?" International Journal of Molecular Sciences 22, no. 3: 992. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22030992

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