Lu, R. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395, 565–574 [2020].
CAS PubMed PubMed Central Google Scholar
Shang, J. et al. Structural basis of receptor recognition by SARS-CoV-2. Nature 581, 221–224 [2020]. Together with Lan, J. et al., this study provides one of two early crystal structures of the SARS-CoV-2 RBD–ACE2 complex, showing how the S protein recognizes its receptor.
CAS PubMed PubMed Central Google Scholar
Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 [2020].
CAS PubMed PubMed Central Google Scholar
Walls, A. C. et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell //doi.org/10.1016/j.cell.2020.02.058 [2020].
Article PubMed PubMed Central Google Scholar
Lan, J. et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 581, 215–220 [2020]. Together with Shang, J. et al., this study provides one of two early crystal structures of the SARS-CoV-2 RBD–ACE2 complex, revealing how the S protein recognizes its receptor.
CAS PubMed Google Scholar
Wang, Q. et al. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 181, 894–904 [2020].
CAS PubMed PubMed Central Google Scholar
Li, W. et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426, 450–454 [2003]. This study identifies ACE2 as the receptor for SARS-CoV.
CAS PubMed PubMed Central Google Scholar
Hofmann, H. et al. Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proc. Natl Acad. Sci. USA 102, 7988–7993 [2005].
CAS PubMed PubMed Central Google Scholar
Hoffmann, M., Kleine-Weber, H. & Pöhlmann, S. A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Mol. Cell 78, 779–784 [2020]. This article provides insight into the function and necessity of the S1–S2 furin-cleavage site for SARS-CoV-2 infection of human lung cells in vitro.
CAS PubMed PubMed Central Google Scholar
Shang, J. et al. Cell entry mechanisms of SARS-CoV-2. Proc. Natl Acad. Sci. USA 117, 11727–11734 [2020].
CAS PubMed PubMed Central Google Scholar
Fehr, A. R. & Perlman, S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol. Biol. 1282, 1–23 [2015].
CAS PubMed PubMed Central Google Scholar
Glowacka, I. et al. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J. Virol. 85, 4122–4134 [2011].
PubMed PubMed Central Google Scholar
Matsuyama, S. et al. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. J. Virol. 84, 12658–12664 [2010]. This study and those by Glowacka et al. [2011] and Shulla et al. [2011] are the first to demonstrate the importance of TMPRSS2 in SARS-CoV infection.
CAS PubMed PubMed Central Google Scholar
Shulla, A. et al. A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J. Virol. 85, 873–882 [2011].
CAS PubMed Google Scholar
Huang, I. C. et al. SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells. J. Biol. Chem. 281, 3198–3203 [2006].
CAS PubMed Google Scholar
Simmons, G. et al. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc. Natl Acad. Sci. USA 102, 11876–11881 [2005]. This study and that by Huang et al. [2006] are the first to identify the role of cathepsin L in processing of the SARS-CoV S protein.
CAS PubMed PubMed Central Google Scholar
Bayati, A., Kumar, R., Francis, V. & McPherson, P. S. SARS-CoV-2 infects cells following viral entry via clathrin-mediated endocytosis. J. Biol. Chem. //doi.org/10.1016/j.jbc.2021.100306 [2021].
Article PubMed PubMed Central Google Scholar
Inoue, Y. et al. Clathrin-dependent entry of severe acute respiratory syndrome coronavirus into target cells expressing ACE2 with the cytoplasmic tail deleted. J. Virol. 81, 8722–8729 [2007].
CAS PubMed PubMed Central Google Scholar
Watanabe, Y., Allen, J. D., Wrapp, D., McLellan, J. S. & Crispin, M. Site-specific glycan analysis of the SARS-CoV-2 spike. Science 369, 330–333 [2020].
CAS PubMed PubMed Central Google Scholar
Harrison, S. C. Viral membrane fusion. Virology 479–480, 498–507 [2015].
PubMed Google Scholar
Wrapp, D. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367, 1260–1263 [2020]. Together with Walls et al. [2020], this study shows cryo-EM structures of the stabilized ectodomain S trimer of SARS-CoV-2, providing molecular insights into its membrane fusion machinery.
CAS PubMed PubMed Central Google Scholar
Gobeil, S. M. et al. D614G mutation alters SARS-CoV-2 spike conformation and enhances protease cleavage at the S1/S2 junction. Cell Rep. 34, 108630 [2021].
CAS PubMed Google Scholar
Yan, R. et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367, 1444–1448 [2020].
CAS PubMed PubMed Central Google Scholar
Xia, S. et al. Inhibition of SARS-CoV-2 [previously 2019-nCoV] infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res. 30, 343–355 [2020].
CAS PubMed PubMed Central Google Scholar
Cai, Y. et al. Distinct conformational states of SARS-CoV-2 spike protein. Science 369, 1586–1592 [2020]. This study provides the first cryo-EM structure of the unmodified full-length S protein of SARS-CoV-2 in both the prefusion conformation and the postfusion conformation.
CAS PubMed Google Scholar
Bangaru, S. et al. Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate. Science 370, 1089–1094 [2020].
CAS PubMed PubMed Central Google Scholar
Zhang, J. et al. Structural impact on SARS-CoV-2 spike protein by D614G substitution. Science 372, 525–530 [2021]. This study provides the cryo-EM structure of the unmodified full-length SARS-CoV-2 S protein with the D614G mutation, supporting its role in stabilizing S1–S2 association.
CAS PubMed PubMed Central Google Scholar
Turonova, B. et al. In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges. Science 370, 203–208 [2020].
CAS PubMed PubMed Central Google Scholar
Ke, Z. et al. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature 588, 498–502 [2020]. This is one of the first reports on SARS-CoV-2 S trimers in situ on the virion surface imaged by cryo-EM and cryo-electron tomography, revealing their high-resolution structure, conformational flexibility and distribution.
CAS PubMed PubMed Central Google Scholar
Yao, H. et al. Molecular architecture of the SARS-CoV-2 virus. Cell 183, 730–738 [2020].
CAS PubMed PubMed Central Google Scholar
Liu, C. et al. The architecture of inactivated SARS-CoV-2 with postfusion spikes revealed by cryo-EM and cryo-ET. Structure 28, 1218–1224 [2020].
CAS PubMed PubMed Central Google Scholar
Kunkel, F. & Herrler, G. Structural and functional analysis of the surface protein of human coronavirus OC43. Virology 195, 195–202 [1993].
CAS PubMed Google Scholar
Schultze, B., Gross, H. J., Brossmer, R. & Herrler, G. The S protein of bovine coronavirus is a hemagglutinin recognizing 9-O-acetylated sialic acid as a receptor determinant. J. Virol. 65, 6232–6237 [1991].
CAS PubMed PubMed Central Google Scholar
Krempl, C., Schultze, B., Laude, H. & Herrler, G. Point mutations in the S protein connect the sialic acid binding activity with the enteropathogenicity of transmissible gastroenteritis coronavirus. J. Virol. 71, 3285–3287 [1997].
CAS PubMed PubMed Central Google Scholar
Zhou, H. et al. Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein. Nat. Commun. 10, 3068 [2019].
PubMed PubMed Central Google Scholar
Chi, X. et al. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science 369, 650–655 [2020]. This is one of the first reports showing that the RBD and the NTD are the two major neutralizing targets on the SARS-CoV-2 S trimer.
CAS PubMed PubMed Central Google Scholar
Liu, L. et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature 584, 450–456 [2020].
CAS PubMed Google Scholar
Wibmer, C. K. et al. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. Nat. Med. 27, 622–625 [2021].
CAS PubMed Google Scholar
Wu, K. et al. Serum neutralizing activity elicited by mRNA-1273 vaccine. N. Engl. J. Med. 384, 1468–1470 [2021].
PubMed Google Scholar
Wang, Z. et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature //doi.org/10.1038/s41586-021-03324-6 [2021].
Article PubMed PubMed Central Google Scholar
Wang, P. et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature //doi.org/10.1038/s41586-021-03398-2 [2021].
Article PubMed PubMed Central Google Scholar
Edara, V. V. et al. Infection and vaccine-induced neutralizing-antibody responses to the SARS-CoV-2 B.1.617 variants. N. Engl. J. Med. //doi.org/10.1056/NEJMc2107799 [2021].
Article PubMed PubMed Central Google Scholar
Wall, E. C. et al. Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. Lancet 397, 2331–2333 [2021].
CAS PubMed PubMed Central Google Scholar
Planas, D. et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature //doi.org/10.1038/s41586-021-03777-9 [2021].
Article PubMed Google Scholar
Sheikh, A. et al. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 397, 2461–2462 [2021].
CAS PubMed PubMed Central Google Scholar
Grabowski, F., Preibisch, G., Gizinski, S., Kochanczyk, M. & Lipniacki, T. SARS-CoV-2 variant of concern 202012/01 has about twofold replicative advantage and acquires concerning mutations. Viruses //doi.org/10.3390/v13030392 [2021].
Article PubMed PubMed Central Google Scholar
Tegally, H. et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 592, 438–443 [2021].
CAS PubMed Google Scholar
Voloch, C. M. et al. Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil. J. Virol. //doi.org/10.1128/JVI.00119-21 [2021].
Article PubMed PubMed Central Google Scholar
Tada, T. et al. SARS-CoV-2 lambda variant remains susceptible to neutralization by mRNA vaccine-elicited antibodies and convalescent serum. Preprint at bioRxiv //doi.org/10.1101/2021.07.02.450959 [2021].
Article PubMed PubMed Central Google Scholar
Li, F., Li, W., Farzan, M. & Harrison, S. C. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 309, 1864–1868 [2005]. This study provides the crystal structure of the SARS-CoV RBD bound to ACE2, illuminating an interface shared by SARS-CoV-2.
CAS PubMed Google Scholar
Wells, H. L. et al. The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus. Virus Evol. 7, veab007 [2021].
CAS PubMed PubMed Central Google Scholar
Tong, P. et al. Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike. Cell //doi.org/10.1016/j.cell.2021.07.025 [2021].
Article PubMed PubMed Central Google Scholar
Hansen, J. et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 369, 1010–1014 [2020].
CAS PubMed PubMed Central Google Scholar
Robbiani, D. F. et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 584, 437–442 [2020].
CAS PubMed PubMed Central Google Scholar
Pinto, D. et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature 583, 290–295 [2020].
CAS PubMed Google Scholar
Yuan, M. et al. A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV. Science 368, 630–633 [2020].
CAS PubMed PubMed Central Google Scholar
Walls, A. C. et al. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc. Natl Acad. Sci. USA 114, 11157–11162 [2017].
CAS PubMed PubMed Central Google Scholar
Fan, X., Cao, D., Kong, L. & Zhang, X. Cryo-EM analysis of the post-fusion structure of the SARS-CoV spike glycoprotein. Nat. Commun. 11, 3618 [2020].
PubMed PubMed Central Google Scholar
Turner, A. J. & Hooper, N. M. The angiotensin-converting enzyme gene family: genomics and pharmacology. Trends Pharmacol. Sci. 23, 177–183 [2002].
CAS PubMed Google Scholar
Donoghue, M. et al. A novel angiotensin-converting enzyme-related carboxypeptidase [ACE2] converts angiotensin I to angiotensin 1–9. Circ. Res. 87, E1–E9 [2000].
CAS PubMed Google Scholar
Crackower, M. A. et al. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 417, 822–828 [2002].
CAS PubMed Google Scholar
Tipnis, S. R. et al. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J. Biol. Chem. 275, 33238–33243 [2000].
CAS PubMed Google Scholar
Lu, G. et al. Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature 500, 227–231 [2013].
CAS PubMed PubMed Central Google Scholar
Yeager, C. L. et al. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature 357, 420–422 [1992].
CAS PubMed PubMed Central Google Scholar
Raj, V. S. et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 495, 251–254 [2013].
CAS PubMed PubMed Central Google Scholar
Li, W. et al. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J. 24, 1634–1643 [2005].
CAS PubMed PubMed Central Google Scholar
Kuba, K. et al. A crucial role of angiotensin converting enzyme 2 [ACE2] in SARS coronavirus-induced lung injury. Nat. Med. 11, 875–879 [2005].
CAS PubMed PubMed Central Google Scholar
Zhou, T. et al. Cryo-EM structures of SARS-CoV-2 spike without and with ACE2 reveal a pH-dependent switch to mediate endosomal positioning of receptor-binding domains. Cell Host Microbe 28, 867–879 e865 [2020].
CAS PubMed PubMed Central Google Scholar
Xiao, T. et al. A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent. Nat. Struct. Mol. Biol. 28, 202–209 [2021].
CAS PubMed PubMed Central Google Scholar
Song, W., Gui, M., Wang, X. & Xiang, Y. Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLoS Pathog. 14, e1007236 [2018].
PubMed PubMed Central Google Scholar
Hou, Y. J. et al. SARS-CoV-2 reverse genetics reveals a variable infection gradient in the respiratory tract. Cell 182, 429–446 [2020]. This study shows that SARS-CoV-2 infection levels in COVID-19 autopsied lungs corresponds to a gradient of ACE2 expression in the upper and lower airways.
CAS PubMed PubMed Central Google Scholar
Sungnak, W. et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat. Med. 26, 681–687 [2020].
CAS PubMed PubMed Central Google Scholar
Wang, Y. et al. A comprehensive investigation of the mRNA and protein level of ACE2, the putative receptor of SARS-CoV-2, in human tissues and blood cells. Int. J. Med. Sci. 17, 1522–1531 [2020].
CAS PubMed PubMed Central Google Scholar
Zou, X. et al. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front. Med. 14, 185–192 [2020].
PubMed Google Scholar
Ahn, J. H. et al. Nasal ciliated cells are primary targets for SARS-CoV-2 replication in early stage of COVID-19. J. Clin. Invest. //doi.org/10.1172/JCI148517 [2021].
Article PubMed PubMed Central Google Scholar
Lee, I. T. et al. ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs. Nat. Commun. //doi.org/10.1038/s41467-020-19145-6 [2020]. This histological study of human donor tissues clarifies ACE2 tissue distribution and establishes that antihypertensive drugs do not potentiate SARS-CoV-2 infection.
Article PubMed PubMed Central Google Scholar
Ye, M. H. et al. Increased ACE 2 and decreased ACE protein in renal tubules from diabetic mice - a renoprotective combination? Hypertension 43, 1120–1125 [2004].
CAS PubMed Google Scholar
Lindner, D. et al. Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases. JAMA Cardiol. 5, 1281–1285 [2020].
PubMed Google Scholar
Zhuang, M.-W. et al. Increasing host cellular receptor-angiotensin-converting enzyme 2 expression by coronavirus may facilitate 2019-nCoV [or SARS-CoV-2] infection. J. Med. Virol. 92, 2693–2701 [2020].
CAS PubMed Google Scholar
Smith, J. C. et al. Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract. Dev. Cell 53, 514–529 [2020].
CAS PubMed PubMed Central Google Scholar
Ziegler, C. G. K. et al. SARS-CoV-2 receptor ACE2 Is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell 181, 1016–1035 [2020].
CAS PubMed PubMed Central Google Scholar
Onabajo, O. O. et al. Interferons and viruses induce a novel truncated ACE2 isoform and not the full-length SARS-CoV-2 receptor. Nat. Genet. 52, 1283–1293 [2020].
CAS PubMed Google Scholar
Baker, S. A., Kwok, S., Berry, G. J. & Montine, T. J. Angiotensin-converting enzyme 2 [ACE2] expression increases with age in patients requiring mechanical ventilation. PLoS ONE 16, e0247060 [2021].
CAS PubMed PubMed Central Google Scholar
Muus, C. et al. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nat. Med. 27, 546–559 [2021].
CAS PubMed Google Scholar
Chen, J. et al. Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation. Aging Cell //doi.org/10.1111/acel.13168 [2020].
Article PubMed PubMed Central Google Scholar
Patanavanich, R. & Glantz, S. A. Smoking is associated with COVID-19 progression: a meta-analysis. Nicotine Tob. Res. 22, 1653–1656 [2020].
CAS PubMed PubMed Central Google Scholar
Zhao, Q. et al. The impact of COPD and smoking history on the severity of COVID-19: a systemic review and meta-analysis. J. Med. Virol. 92, 1915–1921 [2020].
CAS PubMed Google Scholar
Jacobs, M. et al. Increased expression of ACE2, the SARS-CoV-2 entry receptor, in alveolar and bronchial epithelium of smokers and COPD subjects. Eur. Respir. J. //doi.org/10.1183/13993003.02378-2020 [2020].
Article PubMed PubMed Central Google Scholar
Leung, J. M. et al. ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19. Eur. Respir. J. //doi.org/10.1183/13993003.00688-2020 [2020].
Article PubMed PubMed Central Google Scholar
Rossato, M. et al. Current smoking is not associated with COVID-19. Eur. Respir. J. //doi.org/10.1183/13993003.01290-2020 [2020].
Article PubMed PubMed Central Google Scholar
Williamson, E. J. et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 584, 430–436 [2020].
CAS PubMed PubMed Central Google Scholar
Peters, M. C. et al. COVID-19-related genes in sputum cells in asthma. Relationship to demographic features and corticosteroids. Am. J. Respir. Crit. Care Med. 202, 83–90 [2020].
CAS PubMed PubMed Central Google Scholar
Furuhashi, M. et al. Urinary angiotensin-converting enzyme 2 in hypertensive patients may be increased by olmesartan, an angiotensin II receptor blocker. Am. J. Hypertens. 28, 15–21 [2015].
CAS PubMed Google Scholar
Fang, L., Karakiulakis, G. & Roth, M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir. Med. 8, e21 [2020].
CAS PubMed PubMed Central Google Scholar
Patel, A. B. & Verma, A. COVID-19 and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: what is the evidence? JAMA 323, 1769–1770 [2020].
CAS PubMed Google Scholar
Mancia, G., Rea, F., Ludergnani, M., Apolone, G. & Corrao, G. Renin-angiotensin-aldosterone system blockers and the risk of Covid-19. N. Engl. J. Med. 382, 2431–2440 [2020].
CAS PubMed Google Scholar
Reynolds, H. R. et al. Renin-angiotensin-aldosterone system inhibitors and risk of Covid-19. N. Engl. J. Med. 382, 2441–2448 [2020].
CAS PubMed Google Scholar
Mou, H. et al. Mutations derived from horseshoe bat ACE2 orthologs enhance ACE2-Fc neutralization of SARS-CoV-2. PLoS Pathog. 17, e1009501 [2021].
CAS PubMed PubMed Central Google Scholar
Guan, Y. et al. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 302, 276–278 [2003].
CAS PubMed Google Scholar
Lam, T. T. et al. Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins. Nature 583, 282–285 [2020].
CAS PubMed Google Scholar
Liu, P. et al. Are pangolins the intermediate host of the 2019 novel coronavirus [SARS-CoV-2]? PLoS Pathog. 16, e1008421 [2020].
CAS PubMed PubMed Central Google Scholar
Xiao, K. et al. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Nature 583, 286–289 [2020].
CAS PubMed Google Scholar
Peiris, J. S., Guan, Y. & Yuen, K. Y. Severe acute respiratory syndrome. Nat. Med. 10, S88–S97 [2004].
CAS PubMed PubMed Central Google Scholar
Zhou, H. et al. A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein. Curr. Biol. 30, 2196–2203 e2193 [2020].
CAS PubMed PubMed Central Google Scholar
Yan, H. et al. ACE2 receptor usage reveals variation in susceptibility to SARS-CoV and SARS-CoV-2 infection among bat species. Nat. Ecol. Evol. //doi.org/10.1038/s41559-021-01407-1 [2021].
Article PubMed Google Scholar
Liu, Y. et al. Functional and genetic analysis of viral receptor ACE2 orthologs reveals a broad potential host range of SARS-CoV-2. Proc. Natl Acad. Sci. USA //doi.org/10.1073/pnas.2025373118 [2021].
Article PubMed PubMed Central Google Scholar
Jeffers, S. A. et al. CD209L [L-SIGN] is a receptor for severe acute respiratory syndrome coronavirus. Proc. Natl Acad. Sci. USA 101, 15748–15753 [2004].
CAS PubMed PubMed Central Google Scholar
Yang, Z. Y. et al. pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. J. Virol. 78, 5642–5650 [2004].
CAS PubMed PubMed Central Google Scholar
Amraie, R. et al. CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2. ACS Cent. Sci. //doi.org/10.1021/acscentsci.0c01537 [2021].
Article Google Scholar
Khoo, U. S., Chan, K. Y., Chan, V. S. & Lin, C. L. DC-SIGN and L-SIGN: the SIGNs for infection. J. Mol. Med. 86, 861–874 [2008].
CAS PubMed Google Scholar
Geijtenbeek, T. B. et al. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 100, 575–585 [2000].
CAS PubMed Google Scholar
Ichimura, T. et al. KIM-1/TIM-1 is a receptor for SARS-CoV-2 in lung and kidney. Preprint at medRxiv //doi.org/10.1101/2020.09.16.20190694 [2020].
Article Google Scholar
Wang, S. et al. AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells. Cell Res. 31, 126–140 [2021].
CAS PubMed Google Scholar
Amara, A. & Mercer, J. Viral apoptotic mimicry. Nat. Rev. Microbiol. 13, 461–469 [2015].
CAS PubMed PubMed Central Google Scholar
Jemielity, S. et al. TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine. PLoS Pathog. 9, e1003232 [2013].
CAS PubMed PubMed Central Google Scholar
Richard, A. S. et al. AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses. Proc. Natl Acad. Sci. USA 114, 2024–2029 [2017].
CAS PubMed PubMed Central Google Scholar
Marzi, A. et al. DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus. J. Virol. 78, 12090–12095 [2004].
CAS PubMed PubMed Central Google Scholar
Chen, Z. et al. Function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome coronavirus. J. Infect. Dis. 191, 755–760 [2005].
CAS PubMed Google Scholar
Wang, K. et al. CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells. Signal. Transduct. Target. Ther. 5, 283 [2020].
CAS PubMed PubMed Central Google Scholar
Costa, L. B. et al. Insights on SARS-CoV-2 molecular interactions with the renin-angiotensin system. Front. Cell Dev. Biol. 8, 559841 [2020].
PubMed PubMed Central Google Scholar
Shilts, J., Crozier, T. W. M., Greenwood, E. J. D., Lehner, P. J. & Wright, G. J. No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor. Sci. Rep. 11, 413 [2021].
CAS PubMed PubMed Central Google Scholar
Cantuti-Castelvetri, L. et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 370, 856–860 [2020].
CAS PubMed PubMed Central Google Scholar
Daly, J. L. et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science 370, 861–865 [2020].
CAS PubMed Google Scholar
Zhen-Lu, L. & Matthias, B. Neuropilin-1 assists SARS-CoV-2 infection by stimulating the separation of spike protein domains S1 and S2. Biophys. J. //doi.org/10.1016/j.bpj.2021.05.026 [2021].
Article Google Scholar
Camargo, S. M. et al. Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. Gastroenterology 136, 872–882 [2009].
CAS PubMed Google Scholar
Belouzard, S., Chu, V. C. & Whittaker, G. R. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc. Natl Acad. Sci. USA 106, 5871–5876 [2009].
CAS PubMed PubMed Central Google Scholar
Zhang, L. et al. SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nat. Commun. 11, 6013 [2020]. This article shows that enhanced infectivity of the SARS-CoV-2 variants harbouring the D614G S protein mutation is due to a reduced level of premature S1 subunit shedding.
CAS PubMed PubMed Central Google Scholar
Peacock, T. P. et al. The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nat. Microbiol. 6, 899–909 [2021]. This study demonstrates in ferrets a critical in vivo role for the S protein furin-cleavage site in SARS-CoV-2 infection.
CAS PubMed Google Scholar
Limburg, H. et al. TMPRSS2 is the major activating protease of influenza a virus in primary human airway cells and influenza B virus in human type II pneumocytes. J. Virol. //doi.org/10.1128/JVI.00649-19 [2019].
Article PubMed PubMed Central Google Scholar
Shen, L. W., Mao, H. J., Wu, Y. L., Tanaka, Y. & Zhang, W. TMPRSS2: a potential target for treatment of influenza virus and coronavirus infections. Biochimie 142, 1–10 [2017].
CAS PubMed PubMed Central Google Scholar
Sakai, K. et al. TMPRSS2 independency for haemagglutinin cleavage in vivo differentiates influenza B virus from influenza A virus. Sci. Rep. 6, 29430 [2016].
CAS PubMed PubMed Central Google Scholar
Szabo, R. & Bugge, T. H. Type II transmembrane serine proteases in development and disease. Int. J. Biochem. Cell Biol. 40, 1297–1316 [2008].
CAS PubMed Google Scholar
Szabo, R. & Bugge, T. H. Membrane-anchored serine proteases in vertebrate cell and developmental biology. Annu. Rev. Cell Dev. Biol. 27, 213–235 [2011].
CAS PubMed PubMed Central Google Scholar
Qi, F., Qian, S., Zhang, S. & Zhang, Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem. Biophys. Res. Commun. 526, 135–140 [2020].
CAS PubMed PubMed Central Google Scholar
Zhao, Y. et al. Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2. Am. J. Respir. Crit. Care Med. 202, 756–759 [2020].
CAS PubMed PubMed Central Google Scholar
Lukassen, S. et al. SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J. 39, e105114 [2020].
CAS PubMed PubMed Central Google Scholar
Laporte, M. & Naesens, L. Airway proteases: an emerging drug target for influenza and other respiratory virus infections. Curr. Opin. Virol. 24, 16–24 [2017].
CAS PubMed PubMed Central Google Scholar
Ou, T. et al. Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2. PLoS Pathog. 17, e1009212 [2021]. This study uses TMPRSS2 and cathepsin L inhibitors to show that SARS-CoV-2 is more dependent than SARS-CoV on TMPRSS2.
CAS PubMed PubMed Central Google Scholar
Ozono, S. et al. SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity. Nat. Commun. 12, 848 [2021].
CAS PubMed PubMed Central Google Scholar
Zhu, Y. et al. A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry. Nat. Commun. 12, 961 [2021].
CAS PubMed PubMed Central Google Scholar
Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and Is blocked by a clinically proven protease inhibitor. Cell 181, 271–280 [2020]. This is the first study to confirm that processing of the SARS-CoV-2 S protein is, like that of the SARS-CoV S protein, mediated by TMPRSS2.
CAS PubMed PubMed Central Google Scholar
Bosch, B. J., Bartelink, W. & Rottier, P. J. Cathepsin L functionally cleaves the severe acute respiratory syndrome coronavirus class I fusion protein upstream of rather than adjacent to the fusion peptide. J. Virol. 82, 8887–8890 [2008].
CAS PubMed PubMed Central Google Scholar
Ebert, D. H., Deussing, J., Peters, C. & Dermody, T. S. Cathepsin L and cathepsin B mediate reovirus disassembly in murine fibroblast cells. J. Biol. Chem. 277, 24609–24617 [2002].
CAS PubMed Google Scholar
Chandran, K., Sullivan, N. J., Felbor, U., Whelan, S. P. & Cunningham, J. M. Endosomal proteolysis of the ebola virus glycoprotein is necessary for infection. Science 308, 1643 [2005].
CAS PubMed PubMed Central Google Scholar
Shaik, M. M. et al. Structural basis of coreceptor recognition by HIV-1 envelope spike. Nature 565, 318–323 [2019].
CAS PubMed Google Scholar
Campbell, G. R., To, R. K., Hanna, J. & Spector, S. A. SARS-CoV-2, SARS-CoV-1, and HIV-1 derived ssRNA sequences activate the NLRP3 inflammasome in human macrophages through a non-classical pathway. iScience 24, 102295 [2021].
CAS PubMed PubMed Central Google Scholar
Jangra, S. et al. Sterilizing immunity against SARS-CoV-2 infection in mice by a single-shot and lipid amphiphile imidazoquinoline TLR7/8 agonist-adjuvanted recombinant spike protein vaccine. Angew Chem. Int. Ed. 60, 9467–9473 [2021].
CAS Google Scholar
Shi, G. et al. Opposing activities of IFITM proteins in SARS-CoV-2 infection. EMBO J. 40, e106501 [2021].
CAS PubMed Google Scholar
Winstone, H. et al. The polybasic cleavage site in SARS-CoV-2 spike modulates viral sensitivity to type I interferon and IFITM2. J. Virol. //doi.org/10.1128/JVI.02422-20 [2021].
Article PubMed PubMed Central Google Scholar
Pfaender, S. et al. LY6E impairs coronavirus fusion and confers immune control of viral disease. Nat. Microbiol. 5, 1330–1339 [2020].
CAS PubMed PubMed Central Google Scholar
Zhao, X. et al. LY6E restricts entry of human coronaviruses, including currently pandemic SARS-CoV-2. J. Virol. //doi.org/10.1128/JVI.00562-20 [2020].
Article PubMed PubMed Central Google Scholar
Brass, A. L. et al. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 139, 1243–1254 [2009].
PubMed PubMed Central Google Scholar
Huang, I. C. et al. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus. PLoS Pathog. 7, e1001258 [2011].
CAS PubMed PubMed Central Google Scholar
Liu, S. Y., Sanchez, D. J., Aliyari, R., Lu, S. & Cheng, G. Systematic identification of type I and type II interferon-induced antiviral factors. Proc. Natl Acad. Sci. USA 109, 4239–4244 [2012].
CAS PubMed PubMed Central Google Scholar
Schoggins, J. W. et al. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472, 481–485 [2011].
CAS PubMed PubMed Central Google Scholar
Yu, J., Liang, C. & Liu, S. L. Interferon-inducible LY6E protein promotes HIV-1 infection. J. Biol. Chem. 292, 4674–4685 [2017].
CAS PubMed PubMed Central Google Scholar
Hackett, B. A. & Cherry, S. Flavivirus internalization is regulated by a size-dependent endocytic pathway. Proc. Natl Acad. Sci. USA 115, 4246–4251 [2018].
CAS PubMed PubMed Central Google Scholar
Mar, K. B. et al. LY6E mediates an evolutionarily conserved enhancement of virus infection by targeting a late entry step. Nat. Commun. 9, 3603 [2018].
PubMed PubMed Central Google Scholar
Li, X. et al. Emergence of SARS-CoV-2 through recombination and strong purifying selection. Sci. Adv. 6, eabb9153 [2020].
CAS PubMed PubMed Central Google Scholar
Boni, M. F. et al. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic. Nat. Microbiol. 5, 1408–1417 [2020].
CAS PubMed Google Scholar
Menachery, V. D. et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat. Med. 21, 1508–1513 [2015].
CAS PubMed PubMed Central Google Scholar
Zhang, Y. Z. & Holmes, E. C. A genomic perspective on the origin and emergence of SARS-CoV-2. Cell 181, 223–227 [2020].
CAS PubMed PubMed Central Google Scholar
Andersen, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C. & Garry, R. F. The proximal origin of SARS-CoV-2. Nat. Med. 26, 450–452 [2020].
CAS PubMed Google Scholar
Klimstra, W. B. et al. SARS-CoV-2 growth, furin-cleavage-site adaptation and neutralization using serum from acutely infected hospitalized COVID-19 patients. J. Gen. Virol. //doi.org/10.1099/jgv.0.001481 [2020].
Article PubMed PubMed Central Google Scholar
Ogando, N. S. et al. SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology. J. Gen. Virol. 101, 925–940 [2020].
CAS PubMed PubMed Central Google Scholar
Sasaki, M. et al. SARS-CoV-2 variants with mutations at the S1/S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells. PLoS Pathog. 17, e1009233 [2021]. This article shows that the furin-cleavage site in the SARS-CoV-2 S protein is rapidly lost during virus propagation in vitro, which was subsequently confirmed in multiple studies.
CAS PubMed PubMed Central Google Scholar
Pohl, M. O. et al. SARS-CoV-2 variants reveal features critical for replication in primary human cells. PLos Biol. //doi.org/10.1371/journal.pbio.3001006 [2021].
Article PubMed PubMed Central Google Scholar
Mykytyn, A. Z. et al. SARS-CoV-2 entry into human airway organoids is serine protease-mediated and facilitated by the multibasic cleavage site. eLife //doi.org/10.7554/eLife.64508 [2021].
Article PubMed PubMed Central Google Scholar
Lamers, M. M. et al. Human airway cells prevent SARS-CoV-2 multibasic cleavage site cell culture adaptation. eLife 10, e66815 [2021].
CAS PubMed PubMed Central Google Scholar
Korber, B. et al. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 182, 812–827 [2020]. This epidemiological study is first to raise the alarm about the rapid transmission of SARS-CoV-2 harbouring the D614G mutation in the S protein.
CAS PubMed PubMed Central Google Scholar
Jackson, C. B., Zhang, L., Farzan, M. & Choe, H. Functional importance of the D614G mutation in the SARS-CoV-2 spike protein. Biochem. Biophys. Res. Commun. 538, 108–115 [2021].
CAS PubMed Google Scholar
Fernández, A. Structural impact of mutation D614G in SARS-CoV-2 spike protein: enhanced infectivity and therapeutic opportunity. ACS Med. Chem. Lett. 11, 1667–1670 [2020].
PubMed PubMed Central Google Scholar
Michaud, W. A., Boland, G. M. & Rabi, S. A. The SARS-CoV-2 spike mutation D614G increases entry fitness across a range of ACE2 levels, directly outcompetes the wild type, and is preferentially incorporated into trimers. Preprint at bioRxiv //doi.org/10.1101/2020.08.25.267500 [2020].
Article Google Scholar
Juraszek, J. et al. Stabilizing the closed SARS-CoV-2 spike trimer. Nat. Commun. 12, 244 [2021].
CAS PubMed PubMed Central Google Scholar
Weissman, D. et al. D614G spike mutation increases SARS CoV-2 susceptibility to neutralization. Cell Host Microbe 29, 23–31 e24 [2021].
CAS PubMed Google Scholar
Yurkovetskiy, L. et al. Structural and functional analysis of the D614G SARS-CoV-2 spike protein variant. Cell //doi.org/10.1016/j.cell.2020.09.032 [2020].
Article PubMed PubMed Central Google Scholar
Benton, D. J. et al. The effect of the D614G substitution on the structure of the spike glycoprotein of SARS-CoV-2. Proc. Natl Acad. Sci. USA //doi.org/10.1073/pnas.2022586118 [2021].
Article PubMed PubMed Central Google Scholar
Starr, T. N. et al. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell 182, 1295–1310 [2020].
CAS PubMed PubMed Central Google Scholar
Wong, S. K., Li, W., Moore, M. J., Choe, H. & Farzan, M. A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J. Biol. Chem. 279, 3197–3201 [2004]. This study is the first to identify the SARS-CoV RBD.
CAS PubMed Google Scholar
Liu, H. et al. The basis of a more contagious 501Y.V1 variant of SARS-CoV-2. Cell Res. 31, 720–722 [2021].
CAS PubMed PubMed Central Google Scholar
Tian, F. et al. N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2. eLife //doi.org/10.7554/eLife.69091 [2021].
Article PubMed PubMed Central Google Scholar
Gu, H. et al. Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy. Science 369, 1603–1607 [2020].
CAS PubMed PubMed Central Google Scholar
Kidd, M. et al. S-variant SARS-CoV-2 lineage B1.1.7 is associated with significantly higher viral loads in samples tested by ThermoFisher TaqPath RT-qPCR. J. Infect. Dis. //doi.org/10.1093/infdis/jiab082 [2021].
Article PubMed Google Scholar
Leung, K., Shum, M. H., Leung, G. M., Lam, T. T. & Wu, J. T. Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020. Euro Surveill. //doi.org/10.2807/1560-7917.ES.2020.26.1.2002106 [2021].
Article PubMed PubMed Central Google Scholar
Yao, W. et al. Circulating SARS-CoV-2 variants B.1.1.7, 501Y.V2, and P.1 have gained ability to utilize rat and mouse Ace2 and altered in vitro sensitivity to neutralizing antibodies and ACE2-Ig. Preprint at bioRxiv //doi.org/10.1101/2021.01.27.428353 [2021].
Article PubMed PubMed Central Google Scholar
Montagutelli, X. et al. The B1.351 and P.1 variants extend SARS-CoV-2 host range to mice. Preprint at bioRxiv //doi.org/10.1101/2021.03.18.436013 [2021].
Article Google Scholar
Adam, D. What scientists know about new, fast-spreading coronavirus variants. Nature 594, 19–20 [2021].
PubMed Google Scholar
Frazier, L. et al. Spike protein cleavage-activation mediated by the SARS-CoV-2 P681R mutation: a case-study from its first appearance in variant of interest [VOI] A.23.1 identified in Uganda. Preprint at bioRxiv //doi.org/10.1101/2021.06.30.450632 [2021].
Article PubMed PubMed Central Google Scholar
Hoffmann, M. et al. SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell 184, 2384–2393 [2021].
CAS PubMed PubMed Central Google Scholar
Shen, X. et al. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines. Cell Host Microbe //doi.org/10.1016/j.chom.2021.03.002 [2021].
Article PubMed PubMed Central Google Scholar
Greaney, A. J. et al. Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host Microbe 29, 463–476 [2021].
CAS PubMed PubMed Central Google Scholar
Wang, P. et al. Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization. Cell Host Microbe 29, 747–751 [2021].
CAS PubMed PubMed Central Google Scholar
Piccoli, L. et al. Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology. Cell 183, 1024–1042 [2020].
CAS PubMed PubMed Central Google Scholar
Thomson, E. C. et al. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity. Cell 184, 1171–1187 [2021].
CAS PubMed PubMed Central Google Scholar
Chen, R. E. et al. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 27, 717–726 [2021].
CAS PubMed PubMed Central Google Scholar
Baum, A. et al. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science 369, 1014–1018 [2020].
CAS PubMed Google Scholar
Starr, T. N. et al. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Science 371, 850–854 [2021].
CAS PubMed PubMed Central Google Scholar
Andreano, E. et al. SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma. Proc. Natl Acad. Sci. USA //doi.org/10.1073/pnas.2103154118 [2021].
Article PubMed PubMed Central Google Scholar
Deng, X. et al. Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant. Cell 184, 3426–3437 [2021].
CAS PubMed PubMed Central Google Scholar
Cerutti, G. et al. Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite. Cell Host Microbe //doi.org/10.1016/j.chom.2021.03.005 [2021].
Article PubMed PubMed Central Google Scholar
Lok, S. M. An NTD supersite of attack. Cell Host Microbe 29, 744–746 [2021].
CAS PubMed PubMed Central Google Scholar
McCallum, M. et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell 184, 2332–2347 [2021].
CAS PubMed PubMed Central Google Scholar
Suryadevara, N. et al. Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein. Cell 184, 2316–2331 [2021].
CAS PubMed PubMed Central Google Scholar
Li, Q. et al. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell 182, 1284–1294 [2020].
CAS PubMed PubMed Central Google Scholar
Weisblum, Y. et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. eLife //doi.org/10.7554/eLife.61312 [2020].
Article PubMed PubMed Central Google Scholar
Graham, R. L. & Baric, R. S. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. J. Virol. 84, 3134–3146 [2010].
CAS PubMed Google Scholar
Frampton, D. et al. Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study. Lancet Infect. Dis. //doi.org/10.1016/s1473-3099[21]00170-5 [2021].
Article PubMed PubMed Central Google Scholar
Davies, N. G. et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science 372, eabg3055 [2021].
CAS PubMed PubMed Central Google Scholar
Cele, S. et al. Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma. Nature 593, 142–146 [2021].
CAS PubMed Google Scholar
Shen, X. et al. Neutralization of SARS-CoV-2 Variants B.1.429 and B.1.351. N. Engl. J. Med. //doi.org/10.1056/NEJMc2103740 [2021].
Article PubMed PubMed Central Google Scholar
Faria, N. R. et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science 372, 815–821 [2021].
CAS PubMed PubMed Central Google Scholar
Vignier, N. et al. Breakthrough Infections of SARS-CoV-2 Gamma variant in fully vaccinated gold miners, French Guiana, 2021. Emerg. Infect. Dis. //doi.org/10.3201/eid2710.211427 [2021].
Article PubMed PubMed Central Google Scholar
Farinholt, T. et al. Transmission event of SARS-CoV-2 Delta variant reveals multiple vaccine breakthrough infections. Preprint at medRxiv //doi.org/10.1101/2021.06.28.21258780 [2021].
Article PubMed PubMed Central Google Scholar
Starr, T. N., Greaney, A. J., Dingens, A. S. & Bloom, J. D. Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016. Cell Rep. Med. 2, 100255 [2021].
PubMed PubMed Central Google Scholar
Zhou, H. et al. B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies. Preprint at bioRxiv //doi.org/10.1101/2021.03.24.436620 [2021].
Article PubMed PubMed Central Google Scholar
Ferreira, I. et al. SARS-CoV-2 B.1.617 mutations L452 and E484Q are not synergistic for antibody evasion. J. Infect. Dis. //doi.org/10.1093/infdis/jiab368 [2021].
Article PubMed PubMed Central Google Scholar
Palacios, R. et al. Double-blind, randomized, placebo-controlled phase III clinical trial to evaluate the efficacy and safety of treating healthcare professionals with the adsorbed COVID-19 [inactivated] vaccine manufactured by Sinovac - PROFISCOV: a structured summary of a study protocol for a randomised controlled trial. Trials 21, 853 [2020].
CAS PubMed PubMed Central Google Scholar
Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 [2020].
CAS PubMed Google Scholar
Logunov, D. Y. et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet 397, 671–681 [2021].
CAS PubMed PubMed Central Google Scholar
Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 [2021].
CAS PubMed Google Scholar
Barrett, J. R. et al. Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses. Nat. Med. 27, 279–288 [2021].
CAS PubMed Google Scholar
Ella, R. et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. Lancet Infect. Dis. //doi.org/10.1016/s1473-3099[20]30942-7 [2021].
Article PubMed PubMed Central Google Scholar
Mercado, N. B. et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature 586, 583–588 [2020].
CAS PubMed PubMed Central Google Scholar
Keech, C. et al. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N. Engl. J. Med. 383, 2320–2332 [2020].
CAS PubMed Google Scholar
Gosert, R., Kanjanahaluethai, A., Egger, D., Bienz, K. & Baker, S. C. RNA replication of mouse hepatitis virus takes place at double-membrane vesicles. J. Virol. 76, 3697–3708 [2002].
CAS PubMed PubMed Central Google Scholar
Knoops, K. et al. SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. PLoS Biol. 6, e226 [2008].
PubMed PubMed Central Google Scholar
Snijder, E. J. et al. A unifying structural and functional model of the coronavirus replication organelle: tracking down RNA synthesis. PLoS Biol. 18, e3000715 [2020].
CAS PubMed PubMed Central Google Scholar
Stertz, S. et al. The intracellular sites of early replication and budding of SARS-coronavirus. Virology 361, 304–315 [2007].
CAS PubMed Google Scholar
Wolff, G. et al. A molecular pore spans the double membrane of the coronavirus replication organelle. Science 369, 1395–1398 [2020].
CAS PubMed PubMed Central Google Scholar
Goldsmith, C. S. et al. Ultrastructural characterization of SARS coronavirus. Emerg. Infect. Dis. 10, 320–326 [2004].
PubMed PubMed Central Google Scholar
Neuman, B. W. et al. A structural analysis of M protein in coronavirus assembly and morphology. J. Struct. Biol. 174, 11–22 [2011].
CAS PubMed Google Scholar
Schoeman, D. & Fielding, B. C. Coronavirus envelope protein: current knowledge. Virol. J. 16, 69 [2019].
PubMed PubMed Central Google Scholar
Beigel, J. H. et al. Remdesivir for the treatment of covid-19 - final report. N. Engl. J. Med. 383, 1813–1826 [2020].
CAS PubMed Google Scholar
US National Library of Medicine. ClinicalTrials.gov //clinicaltrials.gov/ct2/show/NCT04321096 [2021].
Wang, P. G., Tang, D. J., Hua, Z., Wang, Z. & An, J. Sunitinib reduces the infection of SARS-CoV, MERS-CoV and SARS-CoV-2 partially by inhibiting AP2M1 phosphorylation. Cell Discov. 6, 71 [2020].
CAS PubMed PubMed Central Google Scholar
Zhang, Q. et al. Heparan sulfate assists SARS-CoV-2 in cell entry and can be targeted by approved drugs in vitro. Cell Discov. 6, 80 [2020].
CAS PubMed PubMed Central Google Scholar
Yang, Q. et al. Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration. eLife //doi.org/10.7554/eLife.61552 [2020].
Article PubMed PubMed Central Google Scholar
Zhu, Y., Yu, D., Yan, H., Chong, H. & He, Y. Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity. J. Virol. 94, //doi.org/10.1128/JVI.00635-20 [2020].
Xiu, S. et al. Inhibitors of SARS-CoV-2 entry: current and future opportunities. J. Med. Chem. 63, 12256–12274 [2020].
CAS PubMed Google Scholar
Salazar, E. et al. Treatment of coronavirus disease 2019 patients with convalescent plasma reveals a signal of significantly decreased mortality. Am. J. Pathol. 190, 2290–2303 [2020].
CAS PubMed Google Scholar
Libster, R. et al. Early high-titer plasma therapy to prevent severe Covid-19 in older adults. N. Engl. J. Med. 384, 610–618 [2021].
CAS PubMed Google Scholar
Li, L. et al. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial. JAMA 324, 460–470 [2020].
CAS PubMed Google Scholar
Liu, S. T. H. et al. Convalescent plasma treatment of severe COVID-19: a propensity score-matched control study. Nat. Med. 26, 1708–1713 [2020].
CAS PubMed Google Scholar
Simonovich, V. A. et al. A randomized trial of convalescent plasma in Covid-19 severe pneumonia. N. Engl. J. Med. 384, 619–629 [2021].
CAS PubMed Google Scholar
Joyner, M. J. et al. Convalescent plasma antibody levels and the risk of death from Covid-19. N. Engl. J. Med. 384, 1015–1027 [2021].
CAS PubMed Google Scholar
Wang, C. et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat. Commun. 11, 2251 [2020].
CAS PubMed PubMed Central Google Scholar
Lv, Z. et al. Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody. Science 369, 1505–1509 [2020].
CAS PubMed Google Scholar
Koenig, P.-A. et al. Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape. Science 371, eabe6230 [2021].
CAS PubMed PubMed Central Google Scholar
Schoof, M. et al. An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive spike. Science 370, 1473–1479 [2020].
CAS PubMed PubMed Central Google Scholar
Mahase, E. Covid-19: FDA authorises neutralising antibody bamlanivimab for non-admitted patients. BMJ 371, m4362 [2020].
PubMed Google Scholar
Gottlieb, R. L. et al. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial. JAMA 325, 632–644 [2021].
CAS PubMed PubMed Central Google Scholar
Bhimraj, A. et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 [Infectious Diseases Society of America, 2021].
Chen, Y. et al. ACE2-targeting monoclonal antibody as a “pan” coronavirus blocker in vitro and in a mouse model. Preprint at bioRxiv //doi.org/10.1101/2020.11.11.375972 [2020].
Article PubMed PubMed Central Google Scholar
Tada, T. et al. An ACE2 microbody containing a single immunoglobulin Fc domain is a potent inhibitor of SARS-CoV-2. Cell Rep. 33, 108528 [2020].
CAS PubMed PubMed Central Google Scholar
Monteil, V. et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 181, 905–913 [2020].
CAS PubMed PubMed Central Google Scholar
Sims, J. J. et al. Intranasal gene therapy to prevent infection by SARS-CoV-2 variants. PLoS Pathog. 17, e1009544 [2021].
CAS PubMed PubMed Central Google Scholar
Ferrari, M. et al. Characterisation of a novel ACE2-based therapeutic with enhanced rather than reduced activity against SARS-CoV-2 variants. J. Virol. //doi.org/10.1128/JVI.00685-21 [2021].
Article PubMed PubMed Central Google Scholar
Haschke, M. et al. Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects. Clin. Pharmacokinet. 52, 783–792 [2013].
CAS PubMed Google Scholar
Khan, A. et al. A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Crit. Care //doi.org/10.1186/s13054-017-1823-x [2017].
Article PubMed PubMed Central Google Scholar
Reimer, J. M. et al. Matrix-M adjuvant induces local recruitment, activation and maturation of central immune cells in absence of antigen. PLoS ONE 7, e41451 [2012].
CAS PubMed PubMed Central Google Scholar
Jackson, N. A. C., Kester, K. E., Casimiro, D., Gurunathan, S. & DeRosa, F. The promise of mRNA vaccines: a biotech and industrial perspective. NPJ Vaccines //doi.org/10.1038/s41541-020-0159-8 [2020].
Article PubMed PubMed Central Google Scholar