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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.

          Abstract

          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.

          Abstract

          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 references 70

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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.
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            HIV entry and its inhibition.

             David Chan,  Peter Kim (1998)
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              Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity.

              We investigated the contributions of the structural proteins of severe acute respiratory syndrome (SARS) coronavirus (CoV) to protective immunity by expressing them individually and in combinations from a recombinant parainfluenza virus (PIV) type 3 vector called BHPIV3. This vector provided direct immunization of the respiratory tract, the major site of SARS transmission, replication, and disease. The BHPIV3/SARS recombinants were evaluated for immunogenicity and protective efficacy in hamsters, which support a high level of pulmonary SARS-CoV replication. A single intranasal administration of BHPIV3 expressing the SARS-CoV spike protein (S) induced a high titer of SARS-CoV-neutralizing serum antibodies, only 2-fold less than that induced by SARS-CoV infection. The expression of S with the two other putative virion envelope proteins, the matrix M and small envelope E proteins, did not augment the neutralizing antibody response. In absence of S, expression of M and E or the nucleocapsid protein N did not induce a detectable serum SARS-CoV-neutralizing antibody response. Immunization with BHPIV3 expressing S provided complete protection against SARS-CoV challenge in the lower respiratory tract and partial protection in the upper respiratory tract. This was augmented slightly by coexpression with M and E. Expression of M, E, or N in the absence of S did not confer detectable protection. These results identify S among the structural proteins as the only significant SARS-CoV neutralization antigen and protective antigen and show that a single mucosal immunization is highly protective in an experimental animal that supports efficient replication of SARS-CoV.
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                Author and article information

                Contributors
                sjiang@nybloodcenter.org
                Journal
                Nat Rev Microbiol
                Nat. Rev. Microbiol
                Nature Reviews. Microbiology
                Nature Publishing Group UK (London )
                1740-1526
                1740-1534
                9 February 2009
                2009
                : 7
                : 3
                : 226-236
                Affiliations
                [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
                Article
                BFnrmicro2090
                10.1038/nrmicro2090
                2750777
                19198616
                © 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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                © Springer Nature Limited 2009

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