MedChemExpress compounds prevent neuraminidase N1 via physics- and knowledge-based methods

Area of Science:

• Virology
• Computational Chemistry
• Drug Discovery

Background:

• Influenza A viruses pose a significant global health threat.
• Developing effective neuraminidase inhibitors is crucial for influenza treatment.

Purpose of the Study:

• To identify novel neuraminidase inhibitors for influenza A virus.
• To elucidate the binding mechanisms of potential inhibitors.

Main Methods:

• Machine learning model to screen ~10,000 compounds for neuraminidase inhibitory potential.
• Atomistic simulations (molecular docking and dynamics) to confirm binding affinity.
• Analysis of physical insights into ligand-neuraminidase interactions.

Main Results:

• Five compounds (micronomicin, didesmethyl cariprazine, argatroban, Kgp-IN-1, AY 9944) identified as potential neuraminidase N1 inhibitors.
• Binding affinity was confirmed through molecular docking and dynamics simulations.
• Ten key residues (Glu119, Asp151, Arg152, Trp179, Gln228, Glu277, Glu278, Arg293, Asn295, Tyr402) identified as critical for ligand binding.

Conclusions:

• The study successfully identified novel compounds with potential to inhibit influenza A virus neuraminidase.
• Computational methods provide valuable insights into drug-target interactions for antiviral development.
• Specific amino acid residues play a critical role in the binding of inhibitors to neuraminidase N1.