Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay.

Maywan Hariono,Shaharum Shamsuddin,Sharifah Syed Hassan,Habibah A Wahab,Nornisah Mohamed,Ezatul E Kamarulzaman,Nurshariza Abdullah,K V Damodaran

doi:10.1038/srep38692

Abstract

We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ~0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.

Highlights

Your manuscript entitled "Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay" has been reviewed and the reviewer comments are appended below
The authors should try to ascertain what is the MoA of the compounds, as probably it won't be related to Neuraminidase inhibition
The authors should try to ascertain what is the MoA of the compounds, as probably it won't be related to Neuraminidase inhibition; as such, the conclusions are too generic/unspecific

Summary

Introduction

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Results

Conclusion