Key Takeaways

  • Single Key Interaction: Disrupting one amino acid interaction in herpes glycoprotein B blocks viral entry.
  • AI Insights: Machine learning pinpointed the most critical fusion-driving interaction.
  • Antiviral Potential: Targeting viral entry represents a novel approach for drug development.

Breakthrough in Viral Entry Research

A new study from Washington State University (WSU) uses simulations and machine learning to identify a single high-impact interaction within a viral fusion protein. The long-term goal is that this method may reveal a new potential target for drug development.

Disrupting a Key Molecular Interaction

The researchers found a way to disrupt a key molecular interaction that herpes viruses use to enter cells, a finding that could inform new approaches to antiviral drug discovery. The paper, published in Nanoscale, demonstrates that modulating a single reaction within a viral fusion protein can hinder the virus’s ability to fuse with host cells and initiate infection.

Focus on Glycoprotein B

Glycoprotein B, a fusion protein that herpes viruses rely on to merge with cell membranes, was the core focus of the study. Viral entry is a complicated and multifaceted process that involves thousands of molecular interactions. Therefore, uncovering actionable drug targets becomes very difficult.

Machine Learning and Simulations

The researchers isolated one interaction that played a more prominent role in fusion and demonstrated that not all parts of the protein contribute equally to infectivity. The machine learning and simulations analysed thousands of amino acid interactions within glycoprotein B. Next, the algorithm examines the interactions, and the applied machine learning distinguishes which ones were most critical for enabling the protein to change shape and drive membrane fusion.

Experimental Validation

Experimental validation conducted in WSU’s Department of Veterinary Microbiology and Pathology confirmed the computational predictions. When the team introduced a targeted mutation to one of the identified amino acids, the herpes virus showed a major reduction in its ability to fuse with and enter cells, effectively blocking infection in the experimental system.

Implications for Antiviral Strategies

Overall, this study highlights that viral entry is a potential tractable intervention point. The researchers caution that the current study does not yet provide a complete picture of how altering one interaction affects the structure and dynamics of the entire fusion protein. However, identifying high-impact interactions within entry proteins could open the door to small molecules or biologics designed to prevent infection before it begins, rather than limiting viral spread after the fact.