Catechin inhibition of influenza neuraminidase and its molecular basis with mass spectrometry

• Experimental evidence that catechins bind to inhibit influenza neuraminidase.
• Catechins bind in 430-cavity as shown by mass spectrometry and molecular docking.
• Catechins bind differently to current inhibitors and overcome resistance mutations.

The molecular basis for the antiviral inhibitory properties of three catechins epigallocatechin gallate, epicatechin gallate and catechin-5-gallate derived from green tea was assessed in terms of their ability to interact with influenza neuraminidase. This was investigated using a molecular based MALDI mass spectrometry approach in conjunction with companion inhibition assays employing confocal microscopy. Together with computational molecular docking, all three catechins were found to bind to influenza neuraminidase in the vicinity of a structurally conserved cavity adjacent to residue 430 that has been suggested to be a secondary sialic acid binding site. In doing so, they were effective inhibitors of the enzyme preventing the release of progeny viruses from host cells at inhibitor concentrations (IC50 values) of between 100 and 173 μM. Importantly, their different binding profiles avoid the limitations of existing neuraminidase inhibitors manifested by the evolution of antiviral resistance strains.

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