Antiviral peptides (AVPs) consist of three spirals (green) that lock around the virus’s fusion protein (orange) to prevent the virus from entering the cell. Gelman Labs adds unique β amino acids to peptides (purple), which do not interfere with this critical interaction and make peptides more stable. By designing a small protein or peptide that prevents human para-flu viruses from attaching to cells, researchers have improved a method in rodent models designed to help keep children healthy.
Human para-flu viruses, or HPIVs, are the leading cause of respiratory infections in children, and 30 to 40 percent of diseases (such as chicken coronary disease and pneumonia) are caused by the virus. These viruses can also affect the elderly and people with compromised immune systems.
To make people sick, HPIVs must grab cells and inject their genetic material to start making new viruses. HPIV3 is one of the most common of these viruses. There are currently no approved vaccines or antiviral drugs for HPIV3 infection.
In a study led by Sam Gellman Of The Department Of Chemistry At The University Of Wisconsin-Madison And Anne MoSconA And Matteo PorottO Of Columbia University, ResearcherS Developed A PepTide That Blocks The HPIV3 Attachment Process Based On Years Of PepTide Therapy.
To enter the host cells, HPIVs use specialized fusion proteins, similar to three side-by-side spirals. Early work at Moscone-Porotto’s lab showed that scientists could extract part of the spiral protein from HPIV3, introduce the peptide into the virus and stop the spiral-driven infection process. The peptide itself is a spiral, essentially zip-up with the virus’s spiral, forming a tight bundle of six spiral shapes.
The team first tried to design primitive peptides that were more resistant to protein digestive enzymes in the body that could easily crush and render them ineffective. As a result, Gelman Labs turned to unusual building blocks to create a stronger peptide.
Cells are made of α amino acids to build proteins. But chemists can create β amino acids, similar to each other but with an extra carbon atom. When peptides use these β amino acid components, they usually take different shapes because of the extra atom. This helps peptides evade protein digestive enzymes and survive longer.