Avian influenza is an RNA virus, with subtypes classified by hemagglutanin and neuraminidase (NA) viral surface membrane glycoproteins. There are 9 NA serotypes of influenza A circulating within the avian population (N1-N9). At present, there are two commercially available NA inhibitors, oseltamivir (Tamiflu) and zanamivir (Relenza) and the threat of drug-resistant viruses is driving the development of new NA inhibitors.
The X-ray crystal structure of zanamivir-bound N1 show the C-4 guanidino group of zanamivir located near the 150-loop adjacent to the active site of NA. In this HOT article, Tsu-An Hsu, Chun-Cheng Lin and co-workers report the synthesis and inhibitory activity of a series of zanamivir derivatives with modified C-4 guanidino groups. The new, structurally modified zanamivir analogues retained inhibitory activity against H1N1 and H3N3 avian influenza viruses.
Synthesis of acylguanidine zanamivir derivatives as neuraminidase inhibitors and the evaluation of their bio-activities
Chien-Hung Lin, Tsung-Che Chang, Anindya Das, Ming-Yu Fang, Hui-Chen Hung, Kai-Cheng Hsu, Jinn-Moon Yang, Mark von Itzstein, Kwok Kong T. Mong, Tsu-An Hsu and Chun-Cheng Lin
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