Introduction & Background

Influenza remains a major global health challenge. Respiratory illnesses caused by the influenza virus (Influenzavirus A and B) are responsible for 290,000 to 650,000 deaths annually worldwide. In the United States, seasonal influenza causes approximately 36,000 deaths and over 200,000 hospitalizations each year, with associated healthcare costs nearing $10 billion. In this collaborative research, the focus was on investigating the structural and functional characteristics of neuraminidase, a key enzyme essential for the influenza virus’s biological activity.

Challenge / Objective

The primary objective was to identify potential inhibitors targeting neuraminidase. This was driven by the need to explore new chemical classes beyond the traditional salicylic acid-based inhibitors and address the challenges posed by the virus’s variability.

Approach

The project combined in-silico and in-vitro strategies:

• Computational Screening:

Our team employed a proprietary, state-of-the-art in-silico screening tool to analyze the Ultralight ZINC database within a couple of weeks. A multi-target strategy was implemented to identify hit compounds capable of simultaneously binding to the neuraminidase proteins of both influenza A and B viruses with high affinity.

• Molecular Dynamics Simulations:

The most promising candidates were further validated and assessed for stability through classical molecular dynamics simulations.

• Laboratory Validation:

The top-selected compounds advanced to laboratory (in vitro) testing, which was conducted in collaboration with the Anti-Viral Drug Discovery Laboratory at the Molecular Biology Institute of the National Academy of Sciences.