Combating influenza: natural products as neuraminidase inhibitors

The ever increasing threat of influenza pandemic outbreaks represents a serious concern for public health. Various therapeutic and prophylactic means are available which helps to counter viral infections including vaccines and curative such as zanamivir and oseltamivir. However, with the inception of unfamiliar strains which show resistance to the available drugs manifests the rapid demand for discovery of rational drug as antiviral agents. Neuraminidase, a crucial enzyme for viral replication is the most promising target for new drugs because of its highly conserved residues. Nature provides with a myriad of natural bioactive compounds constituting a plethora of chemical entities that can be useful in drug discovery against influenza. This review is an update on neuraminidase enzyme highlighting its structure, function, catalytic mechanism and its inhibition by natural products. Various approved neuraminidase inhibitors and neuraminidase inhibition assays along with their susceptibility have been described. A discussion on published reports about 267 plant secondary metabolites tested in the past 7 years (2011–2017) for their neuraminidase inhibition activity is presented. Moreover, the recent techniques using QSAR to develop third generation neuraminidase inhibitors have been described. This work summarizes the recent development in experimental and theoretical research based on neuraminidase inhibitors that will help in the discovery of antiviral agents in coming future.