A joint team led by Prof. George Fu Gao and Prof. Feng Gao from Chinese Academy of Sciences (CAS), together with collaborators from Griffith University, have recently elucidated the structural features, NA activities, and sensitivities to neuraminidase inhibitors (NAIs) of two influenza-like viral neuraminidases (NAs) derived from fish and amphibian.
Related results were published in The Proceedings of the National Academy of Science on Oct. 3.
NA is an important target for antiviral development against Influenza virus because it plays a crucial role in releasing newly assembled viruses. Two unique influenza-like viral NA genes derived from the Asiatic toad and spiny eel exhibit highly divergent from all known influenza NAs, raising key questions as to whether the Asiatic toad influenza-like virus NA (tNA) and spiny eel NA (eNA) have canonical NA activities and structures and whether they show sensitivity to NA inhibitors (NAIs). This study identified that both tNA and eNA have neuraminidase activities. However, tNA displayed a high resistance to clinically used NAIs (zanamivir, oseltamivir carboxylate, and peramivir), while eNA was still sensitive to NAIs. The structures of NA–inhibitor complexes revealed that P119 in tNA is the key for resistance to anti-influenza virus drugs.
This is the first time to comprehensively characterize the structure and function of NAs from fish and amphibian-derived influenza-like viruses, which may circulate in the vertebrate.
More importantly, it suggested that we should pay more attention on these influenza-like viruses because their NA molecules may play role in the emergence of NAI resistance.