13 reported that SARS-CoV-2 uses hACE2 as the receptor.Ī Diagram of full-length SARS-CoV-2 S protein with a 3xFLAG tag. While S proteins of SARS-CoV-2 share about 76% and 97% of amino acid identities with SARS-CoV and RaTG13, respectively, the amino acid sequence of potential RBD of SARS-CoV-2 is only about 74% and 90.1% homologous to that of SARS-CoV and RaTG13, respectively. MHV uses mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a) as the receptor 20, and the receptors for SARS-CoV and MERS-CoV are human angiotensin-converting enzyme 2 (hACE2) 21 and human dipeptidyl peptidase 4 (hDPP4) 22, respectively. While RBD of mouse hepatitis virus (MHV) is located at the NTD 14, most of other CoVs, including SARS-CoV and MERS-CoV use C-domain to bind their receptors 15, 16, 17, 18, 19. Depending on the virus, either NTD or C-domain can serve as the receptor-binding domain (RBD). In the structure, N- and C- terminal portions of S1 fold as two independent domains, N-terminal domain (NTD) and C-terminal domain (C-domain) (Fig. Each monomer of trimeric S protein is about 180 kDa, and contains two subunits, S1 and S2, mediating attachment and membrane fusion, respectively. However, the intermediate host or whether there is an intermediate host remains to be determined.ĬoV uses its spike glycoprotein (S), a main target for neutralization antibody, to bind its receptor, and mediate membrane fusion and virus entry. They share about 96% nucleotide sequence identities, suggesting that SARS-CoV-2 might have emerged from a Bat SL-CoV. Phylogenetical analysis revealed that it is a lineage B beta-CoV and closely related to a SARS-like (SL) CoV, RaTG13, discovered in a cave of Yunnan, China, in 2013 13. Viruses were isolated from patients and sequenced. At the end of 2019, a novel coronavirus, named SARS-CoV-2, was found in patients with severe pneumonia in Wuhan, China 10, 11, 12. In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV), a lineage C beta-CoV, was discovered as the causative agent of a severe respiratory syndrome in Saudi Arabia 8, currently with 2494 confirmed cases and 858 deaths 9, it remains endemic in Middle East, and dromedary camel is considered as the zoonotic reservoir host of MERS-CoV.

In 2002–2003, severe acute respiratory syndrome coronavirus (SARS-CoV) 3, 4, a lineage B beta-CoV, emerged from bat and palm civet 5, 6, and infected over 8000 people and caused about 800 deaths 7. Since beginning of this century, there have already been three zoonotic outbreaks of beta-CoVs. They are classified into four genera, alpha-CoV, beta-CoV, gamma-CoV, and delta-CoV 2. Coronaviruses (CoVs) infect human and animals and cause varieties of diseases, including respiratory, enteric, renal, and neurological diseases 1.

Primary antibody cross reactivity