Novel Anti-viral Synthetic Peptides as a Therapeutic Strategy for Venezuelan Equine Encephalitis Virus Infection
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Calangi, Nicholas L
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Abstract
The new world alphavirus, Venezuelan Equine Encephalitis Virus (VEEV), is endemic to the Americas and it is transmitted through vector borne arthropods (1). In humans, viral infection manifests in neurological sequelae, febrile illness, and sometimes death. Key to clinical manifestation of VEEV is viral entry across the blood-brain barrier (BBB) (2,3). The BBB is crucial in facilitating nutrient entry while preventing entry of harmful compounds (2). There are no FDA approved therapeutic strategies to treat VEEV exposure. The overall focus of this research is to develop novel therapeutic solutions to treat VEEV infection. Specifically, in this project, the focus was on synthetic peptides as anti-viral agents. A small-scale library of 45 novel synthetic peptides was created in collaboration with the Massachusetts Institute of Technology and provided to George Mason University for anti-viral evaluation. Host defense peptides (HDPs) have long been studied for their bactericidal qualities during the innate immune response to microbial infection. Recent research has yielded that HDP hold antiviral properties as well and thus the focus of the proposed research is to evaluate the synthetic peptides for their promising anti-viral therapeutic potential (4). The synthetic peptide library was initially screened using a cytotoxicity assay to determine host cell viability following treatment. The peptides demonstrating 80-100% cell viability after twenty-four hours at concentrations between 10-100μg/ml. Nontoxic concentrations as determined by this assay were selected for each peptide for further testing. Following the initial screen, a nanoluciferase reporter virus (TC-83 backbone) was used to evaluate the anti-viral characteristics. Using the nano-luciferase reporter virus, cells were infected and then treated with the peptides at the nontoxic concentrations. Those peptides that demonstrated viral inhibition by 50-70% after twenty-four hours were selected for testing in the primary cells. The combination of studies indicated above have identified several candidate peptides that are well positioned for additional in-depth studies on mechanism on action and subsequent transition to in vivo models.
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VEEV, Antimicrobial peptide, AMPs, Synthetic peptides, Venezuelan Equine Encephalitis virus