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

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 viral surface is densely glycosylated spike (S) protein, which engages angiotensin-converting enzyme 2 (ACE2) mediate host cell entry. However, studies have reported susceptibility in intra- and extrapulmonary immune non-immune cells lacking ACE2, suggesting that S protein may exploit additional receptors infection. Studies demonstrated interactions between innate system, including C-lectin type (CLR), toll-like (TLR) neuropilin-1 (NRP1), receptor glucose regulated 78 (GRP78). Recognition carbohydrate moieties clustered on drive receptor-dependent internalization, accentuate immunopathological inflammation, allow systemic spread infection, independent ACE2. Furthermore, targeting TLRs, CLRs, other (Ezrin dipeptidyl peptidase-4) do not directly engage SARS-CoV-2 but contribute augmented anti-viral immunity clearance, represent therapeutic targets against COVID-19.