Intervirology 2008;51:173–181
(DOI:10.1159/000151530)

Development of Human Single-Chain Antibodies against SARS-Associated Coronavirus

Leung K.M.a, c · Feng D.X.b · Lou J.e · Zhou Y.e · Fung K.P.c · Waye M.M.Y.c · Tsui S.K.W.c · Chan P.K.S.d · Marks J.D.e · Pang S.F.a · Kan Y.W.b
aCK Life Sciences International Inc., Hong Kong, SAR, China; bDepartment of Laboratory Medicine, University of California, San Francisco, Calif., USA; cDepartment of Biochemistry, Croucher Laboratory for Human Genomics, and dDepartment of Microbiology, Chinese University of Hong Kong, Hong Kong, SAR, China; eDepartment of Anesthesia and Pharmaceutical Chemistry, University of California, San Francisco General Hospital, San Francisco, Calif., USA
email Corresponding Author


 goto top of outline Key Words

  • Antibody
  • Severe acute respiratory syndrome
  • Single-chain variable fragment
  • Immunology

 goto top of outline Abstract

The outbreak of severe acute respiratory syndrome (SARS), caused by a distinct coronavirus, in 2003 greatly threatened public health in China, Southeast Asia as well as North America. Over 1,000 patients died of the SARS virus, representing 10% of infected people. Like other coronaviruses, the SARS virus also utilizes a surface glycoprotein, namely the spike protein, to infect host cells. The spike protein of SARS virus consists of 1,255 amino acid residues and can be divided into two sub-domains, S1 and S2. The S1 domain mediates the binding of the virus to its receptor angiotensin-converting enzyme 2, which is abundantly distributed on the surface of human lung cells. The S2 domain mediates membrane fusion between the virus and the host cell. Hence two strategies can be used to block the infection of the SARS virus, either by interfering with the binding of the S1 domain to the receptor or by blocking the fusion of the virus with the cell membrane mediated by the S2 domain. Several antibodies against the S1 domain have been generated and all of them are able to neutralize the virus in vitro and in vivo using animal models. Unfortunately, point mutations have been identified in the S1 domain, so that the virus isolated in the future may not be recognized by these antibodies. As no mutation has been found in the S2 domain indicating that this region is more conserved than the S1 domain, it may be a better target for antibody binding. After predicting the immunogenicity of the epitopes of the S2 domain, we chemically synthesized two peptides and also expressed one of them using a recombinant DNA method. We screened a phage displaying library of human single-chain antibodies (ScFv) against the predicted epitopes and obtained a human ScFv which can recognize the SARS virus in vitro.

Copyright © 2008 S. Karger AG, Basel


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 goto top of outline Author Contacts

K.M. Leung
Room 610, Mong Man Wai Building
Department of Biochemistry, Chinese University of Hong Kong
Hong Kong, SAR (China)
Tel. +852 9420 4960, Fax +852 2651 9324, E-Mail karmanlg@hotmail.com


 goto top of outline Article Information

Received: January 30, 2008
Accepted after revision: May 8, 2008
Published online: August 25, 2008
Number of Print Pages : 9
Number of Figures : 7, Number of Tables : 2, Number of References : 19


 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)

Vol. 51, No. 3, Year 2008 (Cover Date: September 2008)

Journal Editor: Liebert U.G. (Leipzig)
ISSN: 0300–5526 (Print), eISSN: 1423–0100 (Online)

For additional information: http://www.karger.com/INT


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