Structural similarity between HIV-1 gp41 and SARS-CoV S2 proteins suggests an analogous membrane fusion mechanism

Xue Wu Zhang, Yee Leng Yap, Xue Wu Zhang, Yee Leng Yap

Abstract

SARS-associated coronavirus (SARS-CoV) has been identified as the causal agent of a new emerging disease: severe acute respiratory syndrome (SARS). Its spike protein S2 is responsible for mediating fusion of viral and cellular membrane. In this study, we modeled the 3D structure of S2 subunit and compared this model with the core structure of gp41 from HIV-1. We found that SARS-CoV S2 and gp41 share the same two α helices, suggesting that the two viruses could follow an analogous membrane fusion mechanism. Further ligand-binding analysis showed that two inhibitors GGL and D-peptide from HIV-1 gp41 may serve as inhibitors for SARS-CoV entry.

Keywords: Human immunodeficiency virus type 1; Inhibitor; SARS-CoV; Structural similarity.

Copyright © 2004 Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
3D model of SARS-CoV S2.
Fig. 2
Fig. 2
Comparison between gp41 from HIV-1 and SARS-CoV S2. N and C chains of gp41 are colored blue and yellow, respectively. S2 is colored white.
Fig. 3
Fig. 3
(A) Binding interaction between S2 and inhibitor GGL (represented by spacefill). (B) Chemical structure of GGL, its formula is: C5H9NO4.
Fig. 4
Fig. 4
(A) Binding interaction between S2 and D-peptide inhibitor of HIV-1 gp41 (represented by spacefill. (B) Chemical structure for two molecules of D-peptide DAL (5(C3H7NO2)) and DAR (2(C6H15N4O2)).

References

    1. Liu S., Guo T., Ji X., Sun Z. Bioinformatical study on the proteomics and evolution of SARS-CoV. Chinese Science Bulletin. 2003;48:1277–1287.
    1. Gallagher T.M., Buchmeier M.J. Coronavirus spike proteins in viral entry and pathogenesis. Virology. 2001;279:371–374.
    1. Chan D.C., Fass D., Berger J.M., Kim P.S. Core structure of gp41 from the HIV envelope glycoprotein. Cell. 1997;89:263–273.
    1. Gallaher W.R., Garry R.F. Model of the pre-insertion region of the spike (S2) fusion glycoprotein of the human SARS coronavirus: implications for antiviral therapeutics. Virology. 2003 .
    1. Kliger Y., Levanon E.Y. Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy. BMC Microbiology. 2003;3:20–26.
    1. Ginalski K., Elofsson A., Fischer D., Rychlewski L. 3D-Jury: a simple approach to improve protein structure predictions. Bioinformatics. 2003;19:1015–1018.
    1. Sali A., Blundell T.L. Comparative protein modeling by satisfaction of spatial restrains. Journal of Molecular Biology. 1993;234:779–815.
    1. Wallner B., Elofsson A. Can correct protein models be identified? Protein Science. 2003;12:1073–1086.
    1. Zemla A. LGA: a method for finding 3D similarities in protein structures. Nucleic Acids Research. 2003;31:3370–3374.
    1. Thompson J.D., Higgins D.G., Gibson T.J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choice. Nucleic Acids Research. 1994;22:4673–4680.
    1. Jones D.T. Protein secondary structure prediction based on position-specific scoring matrices. Journal of Molecular Biology. 1999;292:195–202.
    1. Zhou G., Ferrer M., Chopra R., Kapoor T.M., Strassmaier T., Weissenhorn W., Skehel J.J., Oprian D., Schreiber S.L., Harrison S.C., Wiley D.C. The structure of an HIV-1 specific cell entry inhibitor in complex with the HIV-1 gp41 trimeric core. Bioorganic and Medicinal Chemistry. 2000;8(9):2219–2227.
    1. Eckert D.M., Malashkevich V.N., Hong L., Carr P.A., Kim P.S. Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket. Cell. 1999;99:103–115.

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