Coronavirus as a possible cause of severe acute respiratory syndrome

Peiris, Malik; St, Lai; Poon, Leo L. M.; Guan, Yi; Yam, Lyc; Lim, Wilina; Nicholls, John M.; Yee, Wks; Wu, Yan; Cheung, MT; Cheng, Vincent Chi-Chung; Chan, KH; Tsang, Dnc; Yung, R; Ng, TK; Yuen, Kwok‐Yung

doi:10.1016/s0140-6736(03)13077-2

Cited by 2,742 publications

(2,371 citation statements)

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“…After 10 days of illness, more than 90% of samples were positive, confirming the findings of other studies (3,6,9) and showing the diagnostic utility of serology in SARS investigation.…”

supporting

confidence: 89%

“…The most reliable laboratory test for the confirmation of SARS is detection of SARS-CoVspecific antibodies (4,8). In Hong Kong, a prospective study of 75 SARS cases demonstrated SARS-CoV IgG seroconversion in 70 (93%) cases by use of an in-house indirect IFA with acetone-fixed SARS-CoV-infected Vero cells, with antibodies detectable at a mean of 20 days (range, 11 to 28) after onset (9). This level of detection was similar to that in the same group's retrospective analysis of 50 cases, where all 32 patients with acute-and convalescent-phase sera demonstrated seroconversion or fourfold rises in SARS-CoV-specific antibody levels by IFA; 280 control sera were negative (8).…”

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confidence: 99%

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Kinetics of Severe Acute Respiratory Syndrome (SARS) Coronavirus-Specific Antibodies in 271 Laboratory-Confirmed Cases of SARS

Zhang

Dong

Zhang

et al. 2004

Clin Vaccine Immunol

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The sensitivities and specificities of an immunofluorescence assay and an enzyme immunoassay for detection of antibodies specific for severe acute respiratory syndrome coronavirus (SARS-CoV) were compared for 148 laboratory-confirmed SARS cases. The appearance and persistence of SARS-CoV-specific antibodies were assessed, with immunoglobulin G detected in 59% of samples collected within 14 days and persisting for 60 to 95 days after the onset of illness. (2-4, 7, 9, 10), although data on the performance of various antibody detection assays and the persistence of SARS-CoV-specific antibodies are lacking.The first aim of this study was to compare the sensitivities and specificities of a commercial immunofluorescence assay (IFA; Euroimmun AG, Lübeck, Germany) and a recombinant double-nucleocapsid antigen sandwich enzyme-linked immunosorbent assay (ELISA; Wantai Biological Pharmacy Enterprise Company, Ltd., Beijing, China) for SARS-CoV-specific immunoglobulin G (IgG) and IgM in patients for whom SARS-CoV RNA had been detected by reverse transcriptase PCR (RT-PCR). The second aim was to assess the timing of the appearance and persistence of SARS-CoV-specific antibodies after the onset of disease.Three hundred four patients fitting the SARS clinical case definition (fever of 38°C or higher, cough or shortness of breath, new pulmonary infiltrates on chest radiography, and close contact with a person with a suspected or probable case) were hospitalized at Ditan Hospital, Beijing, China, between 26 March and 31 May 2003. Probable cases were regarded as laboratory confirmed if SARS-CoV-specific IgG and/or IgM was detected by IFA within 3 weeks of the onset of illness and/or SARS-CoV RNA was detected by RT-PCR within 2 weeks. SARS-CoV infection was laboratory confirmed in 271 of 304 (89.1%) cases, with 33 individuals testing SARS-CoV negative (10.9%; 27 of these had alternative laboratory diagnoses). The mean age of the 271 individuals with laboratoryconfirmed cases was 36 Ϯ 16 years, and they included 92 (33.9%) health care workers and 32 patients with significant underlying illnesses. SARS acquisition in the hospital setting, in either health care workers, inpatients, or hospital visitors, occurred in 112 (41.3%) cases, and a further 62 individuals acquired SARS following exposure at home to family members or friends with hospital-acquired infections. The clinical features were similar to those reported elsewhere (data not shown) (1,3,5,10,11).Comparison of IFA and ELISA for detection of SARS-CoVspecific IgG and IgM. Testing was performed for 148 patients for whom SARS-CoV was detected in respiratory or fecal samples by RT-PCR. SARS-CoV IgM was detected for 117 (79%) people and SARS-CoV IgG was detected for 145 (98%) people by IFA, while IgM was detected for 133 (90%) people and IgG was detected for 120 (82%) people by ELISA. Controls included 105 asymptomatic close contacts of individuals with SARS cases (medical workers) and 90 individuals with chronic hepatitis B (30 cases), hepatitis C (30 cases), or human immunodef...

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“…After 10 days of illness, more than 90% of samples were positive, confirming the findings of other studies (3,6,9) and showing the diagnostic utility of serology in SARS investigation.…”

supporting

confidence: 89%

mentioning

confidence: 99%

Kinetics of Severe Acute Respiratory Syndrome (SARS) Coronavirus-Specific Antibodies in 271 Laboratory-Confirmed Cases of SARS

Zhang

Dong

Zhang

et al. 2004

Clin Vaccine Immunol

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“…A novel coronavirus (CoV) has been isolated and identified as the cause of the severe acute respiratory syndrome (SARS), 1 for which there is currently no effective treatment. The SARS CoV genome sequence has been recently published.…”

mentioning

confidence: 99%

Identifying inhibitors of the SARS coronavirus proteinase

Jenwitheesuk

Samudrala

2003

Bioorganic & Medicinal Chemistry Letters

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Abstract-The Severe Acute Respiratory Syndrome (SARS) is a serious respiratory illness that has recently been reported in parts of Asia and Canada. In this study, we use molecular dynamics (MD) simulations and docking techniques to screen 29 approved and experimental drugs against the theoretical model of the SARS CoV proteinase as well as the experimental structure of the transmissible gastroenteritis virus (TGEV) proteinase. Our predictions indicate that existing HIV-1 protease inhibitors, l-700,417 for instance, have high binding affinities and may provide good starting points for designing SARS CoV proteinase inhibitors. # 2003 Elsevier Ltd. All rights reserved.A novel coronavirus (CoV) has been isolated and identified as the cause of the severe acute respiratory syndrome (SARS), 1 for which there is currently no effective treatment. The SARS CoV genome sequence has been recently published. 2 The structure of the main proteinase, essential for SARS CoV replication, can be deduced from its similarity (43% sequence identity) to the X-ray crystallography structure of the proteinase from the porcine transmissible gastroenteritis virus (TGEV), also a coronavirus. 3 Anand et al., who solved the structure of the TGEV proteinase (PDB code: 1lvo), 4 have produced a model for the SARS CoV proteinase (PDB code: 1p9t and 1pa5) using the former as a template. In addition, they propose a drug discovered to treat the common cold, AG7088, as a good starting point for SARS CoV inhibition. AG7088 by itself has failed to inhibit the SARS CoV in vitro. 5 Here, using simulations, we show that HIV-1 protease inhibitors may provide better starting points than AG7088 for inhibition of the SARS CoV proteinase.Our computational simulation approaches use molecular dynamics (MD) and docking techniques, and have been applied to calculate the binding affinities of HIV-1 protease mutants and their inhibitors. 6 The affinities have then been used to predict resistance/susceptibility for 1800 HIV-1 protease mutants/inhibitor combinations with greater than 90% accuracy. In a similar fashion, we have calculated the binding affinities of a variety of known HIV-1 protease inhibitors to the TGEV main proteinase. Docking calculations were carried out using AutoDock version 3.0.5, with the Larmarckian genetic algorithm (LGA). 7 Since the structures of the TGEV and SARS CoV proteinases-inhibitor complexes have not been obtained, we therefore first performed preliminary docking experiments to identify the potential binding sites of the inhibitors by generating a grid box that is big enough to cover the entire surface of the protein. Docking runs were set to 100 to allow AutoDock to exhaustively find the potential binding sites of each inhibitor. The first ranked docking solution showed that all inhibitors bound to the substrate binding site of the TGEV and SARS proteinases.The protein-inhibitor complexes derived from the preliminary docking step were then immersed in TIP3-water shell and all atoms were allowed to relax using MD simulation. MD simula...

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“…15,16 Sin embargo, el aislamiento del Coronavirus en múltiples laboratorios alrededor del mundo, utilizando las mismas técnicas moleculares en muestras clínicas respiratorias, apuntaba principalmente a este virus como el posible agente etiológico. 8,[17][18][19] Con el cumplimiento de los postulados de Koch en el modelo animal de primate no humano (Macaca fascicularis) se considera al Coronavirus como el agente causal definitivo del SARS. 20 El 24 de marzo, investigadores del Centro para el Control de las Enfermedades Infecciosas de Atlanta (CDC) y en Hong Kong 3,5,11,15 detectaron, por microscopía electrónica, la presencia del mismo Coronavirus encontrado en Canadá en las secreciones respiratorias de pacientes con el SARS.…”

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“…A través de estudios de inmunofluorescencia se ha documentado la formación de anticuerpos contra la nueva variedad de Coronavirus en sueros de la fase aguda y de la fase de convalecencia, en pacientes con diagnóstico del SARS. 8,17,19 Peiris y colaboradores demostraron la presencia del Coronavirus en especímenes respiratorios y en suero en 45 de 50 pacientes, provenientes de cinco diferentes brotes del SARS en Hong Kong. Adicionalmente, por cultivos virales se aisló el Coronavirus en dos de estos pacientes.…”

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