Spike glycoprotein of coronavirus of animals and sars-Cov-2 Pattnaik Bramhadev1,8,9, Kuralayanapalya Suresh Puttahonnappa2, Shivamallu Chandan3, Kollur Shiva Prasad4, Yadav Mahendra P.5, Jacob Siju Susan2, Pandey Awadh B.6, Shyamsundar Kirankere Ananthapadmanabha7, Patil Sharanagouda S.2,* 1Institute of Veterinary Sciences and Animal Husbandry, SoA University, Orissa, India 8Former Director, ICAR-DFMD, Mukteswar, Nainital, India 9FAO Ref Centre for FMD in South Asia, Bhubaneswar, Orissa, India 2ICAR-National Institute of Veterinary Epidemiology and Disease Informatics (NIVEDI), Bengaluru, Karnataka, India 3Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education & Research, Mysore, Karnataka, India 4Department of Sciences, Amrita School of Arts and Sciences, Amrita Vishwa Vidyapeetham, Mysuru Campus, Mysore, Karnataka, India 5Former Vice Chancellor, Sardar Vallabhbhai Patel University of Agriculture & Technology, Meerut, Uttar Pradesh, India 6Former Principal Scientist, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India 7Department of Veterinary Microbiology, Veterinary College (KVAFSU), Hebbal, BengaluruKarnataka, India *Corresponding author E-mail id: sharanspin13@gmail.com
Online published on 7 March, 2023. Abstract Family Coronaviridae comprises genetically and antigenically diverse (both inter- and intra-genotypic) virus populations that infect vertebrates including man, animals and poultry. The coronaviruses (CoVs) have large projections (peplomers/spikes) of about 20nm on the envelope that forms solar corona-like features on the virion, first identified in avian Infectious bronchitis virus (IBV) in 1930s. This followed identification of Mouse Hepatitis Virus (MHV) and porcine Transmissible Gastroenteritis Virus (TGEV), and human CoVs in 1940s and 1960s, respectively. Identification of the Severe Acute Respiratory Syndrome (SARS) agent of 2003 as a CoV was facilitated by visualization of virion surface projections of >20nm in electron microscopy. The virus structure is composed of 4 structural proteins, Spike (180-200kDa; orf2), Envelope (8-10kDa; orf3), Membrane (20-30kDa; orf4) and Nucleoprotein (50-60kDa; orf5). The viral genome also codes for non-structural proteins (up to 16 in SARS-CoV-2) in orf1 (pp1ab), and accessory proteins (up to 9 in SARS-CoV-2) encoded by orfs interspersed between the four structural protein genes/orfs. Different species of CoV primarily vary in the size of ORF2 that codes for the Spike (S) glycoprotein. There are 13 different CoV species prevalent in humans (7) and porcine (6). Determinants of antigenic diversity are primarily located in the Spike (S) glycoprotein/gene. The spike is composed of S protein trimers that bind to host cell receptor (one spike trimer can bind to 3 molecules of host receptor) to initiate virus infection cycle, determines host/cell tropism, susceptibility, transmissibility, and pathogenicity. Most of the information on S gene and the S glycoprotein and their diversity are generated in IBV and MHV models, and of late in SARS-CoV-2. Spike protein differs in conformation among CoV species, that is whether the S protein cleaved or not during virion morphogenesis. In gamma-CoVs and a few beta-CoV, the S protein is cleaved into S1 and S2 subunits by host enzymes in Golgi bodies of host cells before release of new virions. Cleavage of the SARS-CoV-2 spike protein by host protease (furin) to S1 and S2 subunit occurs in host cells prior to release of new virions, or is cleaved following binding of the virus to ACE2. In either way, regarding timing of Spike protein cleavage, presence of polybasic furin sensitive moiety at S1-S2 junction of SARS-CoV-2 escalates transmissibility of the virus; host furin cleavage at S1-S2 junction is required for subsequent cleavage in S2 (S2’ site) by trypsin-like serine protease TMPRSS2, as in MERS-CoV. Polybasic cleavage site between S1 and S2 is absent in SARS-CoV-1, and hence it may not be a determinant of virulence. Upon replication of SARS-CoV-2 in TMPRSS2 deficient cell line, Vero E6, both progeny virion with mutation inactivating the furin sensitive site at the S1-S2 junction, and virion with intact furin sensitive site do generate. The S1 subunit that harbours virus receptor (RBD; receptor binding domain) is more variable, compared to the S2 subunit that mediates virus-host cell fusion. Both N-terminal and C-terminal domains in S1 subunit (NTD and CTD, respectively) have antigenic sites/epitopes that are strain/genus specific, and super antigenic site as well as recurrent deletion regions (RDRs) are contained in the S1-NTD. The S2 subunit is also immunogenic, and anti-S2 antibodies could be cross-reactive between CoV species in a genus. Occurrence of high level of cross-reactive anti-S2 antibodies to hCoV-OC43 and SARS-CoV-2 in Covid-19 convalescent humans could be beneficial in containing inter-human virus transmission/spread. The CoV genome undergoes genetic drift and shift caused by mutation/deletion and recombination that primarily involves Spike gene. Persistent infection of cats with FECoV (FCoV) generates highly pathogenic FIPV having mutations in the S gene. Mutated/truncated S gene may lead to attenuation; the PRCoV is a naturally occurring S gene deletion mutant of TGEV that cross-protects pigs from TGEV. RNA recombination in the S gene may occur upon co-infection of host cells with more than one CoV species. Swapping of S gene between 2 CoV species alters host specificity. The evolution of hCoV-OC43 is attributed to genetic drift in the S gene of BCoV, and homology between E gene of hCoV-OC43 and PHEV is suggestive of RNA recombination between BCoV and PHEV at some stage during evolution of the OC43 virus. Serotype II FCoV is a spike gene recombinant of FCoV- serotype I and canine CoV. As per available information, it appears that gamma-CoV-IBV has the highest spike gene diversity followed by beta-CoV-SARS-CoV-2. Ten neutralizing epitopes/antigenic sites have been delineated in the S glycoprotein of SARS-CoV-2. Complete S gene depicting the prefusion Spike protein has been used to develop effective coronavirus (including SARS-CoV-2) vaccines in different vaccine platforms. The present compilation outlines the major features of the Spike glycoprotein of important CoVs of animals/chicken, and the SARS-CoV-2. Top Keywords BCoV, CCoV, Coronavirus, FIPV, IBV, SARS-CoV-2, Spike gene, Spike glycoprotein, TGEV. Top |