Heptad repeat-derived peptides block the protease-mediated direct entry from cell surface of SARS coronavirus but not entry via endosomal pathway

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

^* To whom correspondence should be addressed. Email: nfujii{at}pharm.kyoto-u.ac.jp. ftaguchi{at}nih.go.jp.

	Abstract

The peptides derived from the heptad repeat (sHRP) of severe acute respiratory syndrome (SARS) coronavirus (SCoV) spike (S) protein 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 infection via a previously-known endosomal entry. To compare the inhibitory effect of sHRP in each pathway, we selected two sHRP, 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 it efficiently inhibited SCoV infection of the protease-mediated cell-surface pathway, but had little effect on the endosomal pathway. This finding suggests that sHRP may effectively prevent the 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 the virus that takes endosomal pathway and one that enters directly from cell surface.