Human parainfluenza viruses, or HPIVs, are the leading cause of childhood respiratory infections, responsible for 30% to 40% of illnesses like croup and pneumonia. The viruses also affect the elderly and people with compromised immune systems.
To sicken people, HPIVs must latch onto cells and inject their genetic material to start making new viruses. HPIV3 is the most prevalent among these viruses. There are currently no approved vaccines or antivirals for HPIV3 infection in people.
In a study led by the Sam Gellman lab in the chemistry department at the University of Wisconsin-Madison, and the lab of Anne Moscona and Matteo Porotto at Columbia University, researchers built upon years of work on peptide treatments to generate one capable of blocking the HPIV3 attachment process.
The researchers published their findings April 7 in the Journal of the American Chemical Society. To enter host cells, HPIVs use specialized fusion proteins that resemble three corkscrews laid side-by-side. Earlier work by the Moscona-Porotto lab showed that scientists could a partial chunk of this corkscrew protein.
As the research team hoped, when they gave the new peptide to cotton rats it lasted much longer in the lungs than the previous version did thanks to its resistance to digestion by enzymes. The peptide was delivered into the rats’ noses.
To test how well the peptide worked to prevent infection, cotton rats received the new peptide before they were exposed to HPIV3. Compared to animals given no antiviral peptides, those given the improved peptide had 10 times fewer viruses in their lungs. And compared to the peptide that was more susceptible to enzymes, the hardier peptide reduced viral load by about three times, suggesting that the new peptide’s ability to avoid digestion in the body helps it better block infection.
The research collaboration is now looking to make second-generation peptides that last even longer in the body. They also want to test how well the modified peptide might block infection by related viruses. That additional research could move the peptide treatment closer to clinical trials.
Victor K. Outlaw et al, Engineering Protease-Resistant Peptides to Inhibit Human Parainfluenza Viral Respiratory Infection, Journal of the American Chemical Society (2021). DOI: 10.1021/jacs.1c01565