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      The spike protein of SARS-CoV — a target for vaccine and therapeutic development


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          Key Points

          • This Review provides an overview on the spike (S) protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) as a target for the development of vaccines and therapeutics for the prevention and treatment of SARS.

          • SARS is a newly emerging infectious disease, caused by SARS-CoV, a novel coronavirus that caused a global outbreak of SARS.

          • SARS-CoV S protein mediates binding of the virus with its receptor angiotensin-converting enzyme 2 and promotes the fusion between the viral and host cell membranes and virus entry into the host cell.

          • SARS-CoV S protein induces humoral and cellular immune responses against SARS-CoV.

          • SARS S protein is the target of new SARS vaccines. These vaccines are based on SARS-CoV full-length S protein and its receptor-binding domain, including DNA-, viral vector- and subunit-based vaccines

          • Peptides, antibodies, organic compounds and short interfering RNAs are additional anti-SARS-CoV therapeutics that target the S protein.

          • The work on SARS-CoV S protein-based vaccines and drugs will be useful as a model for the development of prophylactic strategies and therapies against other viruses with class I fusion proteins that can cause emerging infectious diseases.


          The outbreaks of severe acute respiratory syndrome (SARS) between 2002 and 2004 killed hundreds of people. Vaccines against the SARS coronavirus (SARS-CoV) could protect the population during future outbreaks. In this Review, Shibo Jiang and colleagues describe such vaccines, as well as other therapeutics, based on the SARS-CoV spike protein.


          Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease caused by a novel coronavirus, SARS-coronavirus (SARS-CoV). The SARS-CoV spike (S) protein is composed of two subunits; the S1 subunit contains a receptor-binding domain that engages with the host cell receptor angiotensin-converting enzyme 2 and the S2 subunit mediates fusion between the viral and host cell membranes. The S protein plays key parts in the induction of neutralizing-antibody and T-cell responses, as well as protective immunity, during infection with SARS-CoV. In this Review, we highlight recent advances in the development of vaccines and therapeutics based on the S protein.

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          Most cited references78

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          Characterization of a novel coronavirus associated with severe acute respiratory syndrome.

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          In March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The genome of SARS-CoV is 29,727 nucleotides in length and has 11 open reading frames, and its genome organization is similar to that of other coronaviruses. Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closely related to any of the previously characterized coronaviruses.
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            A novel coronavirus (SCoV) is the etiological agent of severe acute respiratory syndrome (SARS). SCoV-like viruses were isolated from Himalayan palm civets found in a live-animal market in Guangdong, China. Evidence of virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the same market. All the animal isolates retain a 29-nucleotide sequence that is not found in most human isolates. The detection of SCoV-like viruses in small, live wild mammals in a retail market indicates a route of interspecies transmission, although the natural reservoir is not known.
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              Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats.

              Although the finding of severe acute respiratory syndrome coronavirus (SARS-CoV) in caged palm civets from live animal markets in China has provided evidence for interspecies transmission in the genesis of the SARS epidemic, subsequent studies suggested that the civet may have served only as an amplification host for SARS-CoV. In a surveillance study for CoV in noncaged animals from the wild areas of the Hong Kong Special Administration Region, we identified a CoV closely related to SARS-CoV (bat-SARS-CoV) from 23 (39%) of 59 anal swabs of wild Chinese horseshoe bats (Rhinolophus sinicus) by using RT-PCR. Sequencing and analysis of three bat-SARS-CoV genomes from samples collected at different dates showed that bat-SARS-CoV is closely related to SARS-CoV from humans and civets. Phylogenetic analysis showed that bat-SARS-CoV formed a distinct cluster with SARS-CoV as group 2b CoV, distantly related to known group 2 CoV. Most differences between the bat-SARS-CoV and SARS-CoV genomes were observed in the spike genes, ORF 3 and ORF 8, which are the regions where most variations also were observed between human and civet SARS-CoV genomes. In addition, the presence of a 29-bp insertion in ORF 8 of bat-SARS-CoV genome, not in most human SARS-CoV genomes, suggests that it has a common ancestor with civet SARS-CoV. Antibody against recombinant bat-SARS-CoV nucleocapsid protein was detected in 84% of Chinese horseshoe bats by using an enzyme immunoassay. Neutralizing antibody to human SARS-CoV also was detected in bats with lower viral loads. Precautions should be exercised in the handling of these animals.

                Author and article information

                Nat Rev Microbiol
                Nat. Rev. Microbiol
                Nature Reviews. Microbiology
                Nature Publishing Group UK (London )
                9 February 2009
                : 7
                : 3
                : 226-236
                [1 ]GRID grid.250415.7, ISNI 0000 0004 0442 2075, Lindsley F. Kimball Research Institute, New York Blood Center, ; 310 East 67th Street, New York, 10065 New York USA
                [2 ]State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071 China
                [3 ]GRID grid.284723.8, ISNI 0000 0000 8877 7471, School of Pharmaceutical Sciences, Southern Medical University, ; Guangzhou, 510515 China
                [4 ]GRID grid.194645.b, ISNI 0000000121742757, Department of Microbiology, , University of Hong Kong, Pokfulam, ; Hong Kong SAR, China
                © Nature Publishing Group 2009

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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