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.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, glycosylation, angiotensin-converting enzyme 2, Toll-like receptor, Spike protein, c-lectin type receptor, glucose-regulated protein 78, N-glycans, mannose receptor, 【초록키워드】 coronavirus disease, Inflammation, S protein, susceptibility, Infection, TLRs, viral clearance, GRP78, immune, Dipeptidyl peptidase-4, innate immune system, Spread, Protein, Health, NRP1, receptor, Glucose, SARS-CoV-2 S protein, Coronavirus-2, CLR, Interaction, COVD-19, therapeutic target, host cell, acute respiratory syndrome, Recognition, viral surface, CLRs, carbohydrate, Anti-viral immunity, ezrin, TLR, Cell, independent, catastrophic, Occurrence, responsible, reported, contribute, demonstrated, regulated, non-immune, the S protein, glycosylated, immunopathological, engage, 【제목키워드】 Multiple, Can,