Host-based anti-microbial peptides as therapeutic strategies for alphavirus infections
Abstract
Encephalitic alphaviruses, such as Venezuelan (VEEV), Eastern (EEEV), and Western (WEEV) Equine Encephalitis Viruses, are important threats to the warfighter, particularly when transmitted as aerosols. Currently, we lack effective therapeutic strategies to treat the warfighter following exposure to aerosolized alphavirus. Antimicrobial peptides (AMPs) have demonstrated significant success in controlling bacterial infections and preventing long-term damage resulting from inflammation. We propose to explore synthetic AMPs to control alphavirus multiplication, reduce inflammation, and protect the integrity of the blood brain barrier (BBB). Our approach is based on the success of AMPs in controlling the multiplication of several enveloped viruses, including Influenza and Vaccinia viruses in cell culture and in vivo (1-9). Data from ongoing studies in our laboratory suggest that AMPs can control VEEV multiplication in infected cells. Our approach will focus on a targeted evolutionary strategy for AMP development by an iterative process involving pattern recognition and machine learning algorithms. This strategy will be used to generate AMPs that inhibit alphaviruses and protect the BBB from inflammatory damage. Our team members from MIT have successfully employed this approach to design AMPs that inhibit bacterial agents and exhibit an immunomodulatory phenotype. AMPs designed for antiviral and anti-inflammatory activity will be evaluated for broad spectrum efficacy in cell culture and small animal models of alphavirus infection.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- HDTRA11810041
Entities
People
- Aarthi Narayanan
Organizations
- Defense Threat Reduction Agency
- George Mason University