Coronavirus replication and pathogenesis: Implications for the recent outbreak of severe acute respiratory syndrome (SARS), and the challenge for vaccine development

Navas-Martín, Sonia; Weiss, Susan R.

doi:10.1080/13550280490280292

Cited by 53 publications

(55 citation statements)

References 129 publications

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“…Live attenuated CoVs, killed CoVs, DNA vaccines and viral-vectored vaccines have all been used to successfully vaccinate against animal CoVs (Cavanagh, 2003;Holmes, 2003;Navas-Martin & Weiss, 2004). Spike (S) protein has been shown to be involved in CoV pathogenesis and several groups have developed SARS vaccines based on the SARS-CoV S protein as a target (See et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

See

Petric

Lawrence

et al. 2008

Journal of General Virology

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Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage. INTRODUCTIONSevere acute respiratory syndrome (SARS) caused 8098 reported cases and 774 deaths in 26 countries (WHO, 2004a) in a single autumn-to-spring period from 2002 to 2003, and had significant effects on the global economy. Serological evidence suggests zoonotic transmission of SARS coronavirus (CoV) into the human population for several years before this outbreak (Zheng et al., 2004); transmission to humans has continued, resulting in at least four independent non-laboratory associated cases in (Che et al., 2006Fleck, 2004; Guan et al., 2005; WHO, 2004b). The aetiological agent of SARS has been identified as a novel human CoV by sequencing of its genome (Marra et al., 2003;Rota et al., 2003) and by experimental infection of macaques to fulfil Koch's postulates (Fouchier et al., 2003). It is of particular concern as a zoonosis because it can replicate in a large number of animals including cats, pigs, ferrets, foxes, monkeys and rats (Chen et al., 2005; et al., 1996;Olsen, 1993). Although antibodies to CoV N proteins have no virus-neutralizing activity, there is evidence that the protein may provide protection in vivo by induction of cell-mediated immunity, although it has also been suggested to induce eosinophilic infiltrates resulting in immunopathology (Deming et al., 2006;Enjuanes et al., 1995; Stohlman et al., 1995;Wesseling et al., 1993). N protein has been shown to generate CoV-specific CD8 + T cells (Boots et al., 1991;Seo et al., 1997; Stohlman et al., 1993 Stohlman et al., , 1995; it also provides protection in animals in response to infection by animal CoV (Collisson et al., 2000;Seo et al., 1997). In addition, vaccination with SARS N protein decre...

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Section: Introductionmentioning

confidence: 99%

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

See

Petric

Lawrence

et al. 2008

Journal of General Virology

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“…Data from these vaccines provide much of our current knowledge about the efficacy of anti-coronavirus vaccines. Live attenuated coronaviruses, killed coronaviruses, DNA vaccines and recombinant viral vector vaccines have all been used to successfully vaccinate animals [39,47,48]. Furthermore, data show that a large number of patients infected with the SARS-CoV do recover from the infection.…”

Section: Potential For Vaccine Developmentmentioning

confidence: 97%

Rapid Response Research - SARS Coronavirus Vaccines and Application of Processes to Other Emerging Infectious Diseases

See¹,

Roper²,

Brunham³

et al. 2005

CIR

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The near pandemic caused by the severe acute respiratory syndrome (SARS) emphasized that new and emerging infectious diseases not only continue to plague the world but also how the scientific community can unite to rapidly identify the causative agent and develop strategies such as vaccines to control its spread. The availability of the SARS coronavirus (SARS-CoV) genome sequence paved the way for the identification of recombinant vaccine candidates for SARS. Based on previous successful animal CoV vaccines, vaccinologists focused on the major CoV structural proteins such as the spike (S) and nucleocapsid (N) proteins as vaccine candidates. We will review the vaccine strategies SARS researchers have used and discuss current SARS animal models used for vaccine evaluation. The small number of SARS cases in 2004 has raised questions about whether SARS will return as a pandemic and the cost-effectiveness of testing a SARS vaccine in human clinical trials. Finally, the SARS outbreaks identified several gaps in the response to emerging infectious diseases. The SARS Accelerated Vaccine Initiative (SAVI) was established to provide rapid solutions to a public health emergency and to develop a new research paradigm for vaccine development for newly emerging and reemerging infectious diseases.

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“…Derivatives of etacrynic acid (35), a well-known diuretic drug which contains an activated double bond, were chosen as potential non-peptidic leads by Kaeppler et al owing to their activity towards the cysteine protease papain [82]. Etacrynic acid tert-butylamide (36) was identified as the most promising inhibitor by HPLC-based assay whereas the parent compound, etacrynic acid, showed limited inhibition of the coronaviral M pro . The docking study of etacrynic acid tert-butylamide suggests that the compound spans across the binding pockets with the tert-butyl group located in the hydrophobic S4 pocket, the dichlorobenzyl moiety located close to S3 and the terminal During the SARS outbreak, it was being widely believed that Isatis indigotica root and phenolic Chinese herbs could be used to prevent SARS infection.…”

Section: (B) Non Peptide Compoundsmentioning

confidence: 99%

“…The life cycle of SARS-CoV replication has been extensively reviewed [33][34][35][36]. SARS-CoV is a positive-sense RNA virus containing 29,727 nucleotide residues with a total of 14 open reading frames (ORFs) as predicted by Thiel et al [35].…”

Section: Current Progress In Anti-sars-cov Drug Researchmentioning

confidence: 99%

Antiviral Drug Discovery Against SARS-CoV

Wu¹,

Lin²,

Hsu³

et al. 2006

CMC

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Severe Acute Respiratory Syndrome (SARS) is a life-threatening infectious disease caused by SARS-CoV. In the 2003 outbreak, it infected more than 8,000 people worldwide and claimed the lives of more than 900 victims. The high mortality rate resulted, at least in part, from the absence of definitive treatment protocols or therapeutic agents. Although the virus spreading has been contained, due preparedness and planning, including the successful development of antiviral drugs against SARS-CoV, is necessary for possible reappearance of SARS. In this review, we have discussed currently available strategies for antiviral drug discovery and how these technologies have been utilized to identify potential antiviral agents for the inhibition of SARS-CoV replication. Moreover, progress in the drug development based on different molecular targets is also summarized, including 1) Compounds that block the S protein-ACE2-mediated viral entry; 2) Compounds targeting SARS-CoV M(pro); 3) Compounds targeting papain-like protease 2 (PLP2); 4) Compounds targeting SARS-CoV RdRp; 5) Compounds targeting SARS-CoV helicase; 6) Active compounds with unspecified targets; and 7) Research on siRNA. This review aims to provide a comprehensive account of drug discovery on SARS. The experiences with the SARS outbreak and drug discovery would certainly be an important lesson for the drug development for any new viral outbreaks that may emerge in the future.

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Coronavirus replication and pathogenesis: Implications for the recent outbreak of severe acute respiratory syndrome (SARS), and the challenge for vaccine development

Cited by 53 publications

References 129 publications

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

Rapid Response Research - SARS Coronavirus Vaccines and Application of Processes to Other Emerging Infectious Diseases

Antiviral Drug Discovery Against SARS-CoV

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