The zoonotic transmission of highly pathogenic coronaviruses into the human population is a pressing concern highlighted by the ongoing SARS-CoV-2 pandemic. Recent work has helped to illuminate much about the mechanisms of SARS-CoV-2 entry into the cell, which determines host- and tissue-specific tropism, pathogenicity, and zoonotic transmission. Here we discuss current findings on the factors governing SARS-CoV-2 entry. We first reviewed key features of the viral spike protein (S) mediating fusion of the viral envelope and host cell membrane through binding to the SARS-CoV-2 receptor, angiotensin-converting enzyme 2. We then examined the roles of host proteases including transmembrane protease serine 2 and cathepsins in processing S for virus entry and the impact of this processing on endosomal and plasma membrane virus entry routes. We further discussed recent work on several host cofactors that enhance SARS-CoV-2 entry including Neuropilin-1, CD147, phosphatidylserine receptors, heparan sulfate proteoglycans, sialic acids, and C-type lectins. Finally, we discussed two key host restriction factors, i.e. , interferon-induced transmembrane proteins and lymphocyte antigen 6 complex locus E, which can disrupt SARS-CoV-2 entry. The features of SARS-CoV-2 are presented in the context of other human coronaviruses, highlighting unique aspects. In addition, we identify the gaps in understanding of SARS-CoV-2 entry that will need to be addressed by future studies.
【저자키워드】 SARS-CoV-2, ACE2, TMPRSS2, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, endocytosis, virus entry, membrane fusion, ISG, Interferon-stimulated gene, ACE2, angiotensin converting enzyme 2, NRP-1, neuropilin-1, SARS-CoV, severe acute respiratory syndrome coronavirus, MERS-CoV, Middle East respiratory syndrome coronavirus, RNA virus, cathepsin B, entry cofactor, virus receptor, Cat B/L, cathepsin B/L, CD147, cluster of differentiation 147, Cyp A/B, cyclophilin A/B, HCoV, human coronavirus, HSPG, heparin sulfate proteoglycan, IFITM, interferon-induced transmembrane proteins, Ly6E, lymphocyte antigen 6E, MHV, mouse hepatitis virus, PS, phosphatidylserine, RBD, receptor binding domain, TIM-1, T-cell immunoglobulin and mucin domain 1, TMPRSS2, transmembrane protease, serine 2, 【초록키워드】 SARS-CoV-2 pandemic, interferon, protease, angiotensin-converting enzyme 2, SARS-CoV-2 receptor, Spike protein, Antigen, CD147, heparan sulfate, lymphocyte, Viral, virus entry, Factors, receptors, Neuropilin-1, receptor, pathogenicity, transmembrane protease serine 2, Phosphatidylserine, mechanism, human coronaviruses, neuropilin, binding, cathepsin, Angiotensin-converting enzyme, angiotensin, host proteases, the cell, human population, cofactors, host cell, cofactor, sulfate, sialic acids, viral spike protein, Factor, Cathepsins, Serine, locus, host cell membrane, SARS-CoV-2 entry, complex, transmembrane, host protease, zoonotic transmission, plasma membrane, transmembrane protein, proteoglycans, viral envelope, highly pathogenic, C-type lectins, serine 2, Host, recent, feature, Cell, ENhance, identify, examined, addition, coronavirus, determine, unique, addressed, disrupt, highlighting, the SARS-CoV-2, 【제목키워드】 Factor, Host, role,