Shortly after synthesis, the S glycoprotein monomers trimerize, which might be thought to facilitate the transport from the ER to the Golgi complex. Co-translationally, N-linked, high-mannose oligosaccharide side chains are added during synthesis ( 18, 19). A single stop-transfer, membrane-spanning sequence located at the C terminus of the S protein prevents it from being fully released into the lumen of the ER and subsequent secretion from the infected cell ( 16, 17). The unprocessed precursor harbors an endoplasmic reticulum (ER) signal sequence located at the N terminus, which targets the S glycoprotein to the RER membrane and is removed by cellular signal peptidases in the lumen of the ER ( 14, 15). The SARS-CoV-2 S glycoprotein is synthesized as a 1273-amino acid polyprotein precursor on the rough endoplasmic reticulum (RER) ( Figure 1) ( 13). Synthesis, Processing and Trafficking of the SARS-CoV-2 S Glycoprotein Here, we provide a comprehensive overview of the wealth of research related to the SARS-CoV-2 S glycoprotein biosynthesis, structure, function, and antigenicity, aiming to provide useful insights into the design and development of the S protein-based vaccines as well as therapeutics to prevent or treat the ongoing global spread of SARS-CoV-2/COVID-19. Because of its central roles in viral infection and eliciting protective humoral and cell-mediated immune responses in hosts during infection ( 10), the S protein is the primary target for vaccine design as well as antiviral therapeutics ( 12). The surface-exposed location of the S glycoprotein not only allows it to carry out membrane fusion but also renders it a direct target for host immune responses, making it the major target of neutralizing antibodies ( 11). Membrane fusion is mediated by the large type I transmembrane S glycoprotein on the viral envelope and the cognate receptor on the surface of host cells ( 8– 10). Enveloped CoVs entering host cells and initiating infection is achieved through the fusion of viral and cellular membranes ( 6, 7). The virus has spread rapidly and sustainably around the global resulting in over twenty-one million cases and more than 750,000 deaths as of Aug( 4).Ĭoronaviruses (CoVs) are enveloped positive-sense RNA viruses ( 5). The etiological agent of COVID-19 is a new member of the Coronaviridae family that is closely related to severe acute respiratory syndrome coronavirus (SARS-CoV) and was recently referred to as SARS-CoV-2 by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses ( 3). The coronavirus disease 2019 (COVID-19) global pandemic represents an unprecedented public health, social and economic challenge ( 1, 2). In this review, we highlight and describe the recent progress that has been made in the biosynthesis, structure, function, and antigenicity of the SARS-CoV-2 S glycoprotein, aiming to provide valuable insights into the design and development of the S protein-based vaccines as well as therapeutics. In the light of its crucial roles in viral infection and adaptive immunity, the S protein is the focus of most vaccine strategies as well as therapeutic interventions. Surface location of the S glycoprotein renders it a direct target for host immune responses, making it the main target of neutralizing antibodies. The S glycoprotein plays essential roles in virus attachment, fusion and entry into the host cell. Like other coronaviruses, the SARS-CoV-2 genome encodes spike (S) glycoproteins, which protrude from the surface of mature virions. The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a grave threat to global public health and imposes a severe burden on the entire human society. 2Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.1Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.Liangwei Duan 1,2 Qianqian Zheng 1,2 Hongxia Zhang 1,2 Yuna Niu 1,2 Yunwei Lou 1,2 Hui Wang 1,2*
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