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Heptad Repeat-Derived Peptides Block Protease-Mediated Direct Entry from the Cell Surface of Severe Acute Respiratory Syndrome Coronavirus but Not Entry via the Endosomal Pathway

Makoto Ujike,^1, Hiroki Nishikawa,^2, Akira Otaka,³ Naoki Yamamoto,⁴ Norio Yamamoto,⁴ Masao Matsuoka,⁵ Eiichi Kodama,⁵ Nobutaka Fujii,^2,5* and Fumihiro Taguchi^1*

Department of Virology III, National Institute of Infectious Disease, Gakuen 4-7-1, Musashi-murayama, Tokyo 208-0011, Japan,¹ Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan,² Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770-8505, Japan,³ Department of Molecular Virology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan,⁴ Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan⁵

Received 6 August 2007/ Accepted 6 October 2007

The peptides derived from the heptad repeat (HRP) of severe acute respiratory syndrome coronavirus (SCoV) spike protein (sHRPs) are known to inhibit SCoV infection, yet their efficacies are fairly low. Recently our research showed that some proteases facilitated SCoV's direct entry from the cell surface, resulting in a more efficient infection than the previously known infection via endosomal entry. To compare the inhibitory effect of the sHRP in each pathway, we selected two sHRPs, which showed a strong inhibitory effect on the interaction of two heptad repeats in a rapid and virus-free in vitro assay system. We found that they efficiently inhibited SCoV infection of the protease-mediated cell surface pathway but had little effect on the endosomal pathway. This finding suggests that sHRPs may effectively prevent infection in the lungs, where SCoV infection could be enhanced by proteases produced in this organ. This is the first observation that HRP exhibits different effects on virus that takes the endosomal pathway and virus that enters directly from the cell surface.

Published ahead of print on 17 October 2007.

M.U. and H.N. contributed equally to this work.