Inhibition of Human Coronaviruses by RNAi

Since it became clear that the outbreak of SARS beginning 2003 is caused by the virus currently known as SARS-coronavirus (SARS-CoV), researchers have tried to find cures for this new virus. It was shown that both shRNAs and siRNAs could efficiently block SARS-CoV replication in tissue culture systems (He et al. 2003; Lu et al. 2004a; Wang et al. 2004b; Zhang et al. 2004b). In these studies, the main target was the polymerase gene, whereas one paper describes inhibition of SARS-CoV by targeting the spike protein, which is essential for particle formation and entry (Zhang et al. 2004b). Additionally, replication of the newly discovered human coronavirus NL63, HCoV-NL63 (Van der Hoek et al. 2004), could also be inhibited by siRNAs that target the spike gene (Pyrc et al. in preparation). Because SARS is a disease of the upper airways and lungs, it could be relatively easy to administer therapeutic siRNAs. For influenza virus, HRSV and HPIV, it has been shown that virus replication in the lungs of mice can be inhibited by intravenous or intranasal administration of siRNAs/shRNAs (Bitko et al. 2005; Ge et al. 2004; Tompkins et al. 2004; Zhang et al. 2005). Following a similar route, siRNAs against SARS-CoV might be effective as a new antiviral therapeutic.

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