Abstract：
:Antiviral medication is used for the treatment of severe influenza infections, of which the neuraminidase inhibitors (NAIs) are the most effective drugs, approved so far. Here, we investigated the antiviral efficacy of the peptidomimetic furin inhibitor MI-701 in combination with oseltamivir carboxylate and ribavirin against the infection of highly pathogenic avian influenza viruses (HPAIV) that are activated by the host protease furin. Cell cultures infected with the strains A/Thailand/1(KAN-1)/2004 (H5N1) and A/FPV/Rostock/1934 (H7N1) were treated with each agent alone, or in double and triple combinations. MI-701 alone achieved a concentration-dependent reduction of virus propagation. Double treatment of MI-701 with oseltamivir carboxylate and triple combination with ribavirin showed synergistic inhibition and a pronounced delay of virus propagation. MI-701 resistant mutants were not observed. Emergence of NA mutation H275Y conferring high oseltamivir resistance was significantly delayed in the presence of MI-701. Our data indicate that combination with a potent furin inhibitor significantly enhances the therapeutic efficacy of conventional antivirals drugs against HPAIV infection.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Lu Y,Hardes K,Dahms SO,Böttcher-Friebertshäuser E,Steinmetzer T,Than ME,Klenk HD,Garten Wdoi
10.1016/j.antiviral.2015.05.006subject
Has Abstractpub_date
2015-08-01 00:00:00pages
89-100eissn
0166-3542issn
1872-9096pii
S0166-3542(15)00126-6journal_volume
120pub_type
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