Brilacidin as a Broad-Spectrum Inhibitor of Enveloped, Acutely Infectious Viruses



Anderson, Carol

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Rift Valley Fever virus (RVFV) is a Bunyavirus known to cause severe disease in livestock. Its zoonotic capability makes it a serious threat as it has become endemic in many parts of the world. While primarily spread through Aedes and Culex mosquitos, it can also be transmitted via aerosol and direct contact with infected bodily fluids. In humans it is known to cause hemorrhagic fever and liver failure. There are currently no FDA approved treatments for RVFV, making it an area of serious concern for the development and implementation of novel therapeutics. In this investigation Brilacidin (BRL), a defensin mimetic, was tested against RVFV among other viruses such as Sindbis (SINV) and an Echovirus. BRL was previously designed for antibiotic-resistant bacteria and its amphipathic nature enables it to disrupt membranes. It has been shown to be effective on both gram-positive and gram-negative bacteria, including MRSA. This work on bacteria has since been expanded to enveloped viruses such as SARS-COV-2, the causative agent of COVID-19. RVFV was tested in Human small airway epithelial cells (HSAECs) via plaque assay, and then this was repeated in other cell lines including Huh7s and HepG2s. Cytotoxicity analyses were conducted to determine cell viability when BRL was applied to the cells. Through direct viral treatment, a significant decrease was seen in viral load, that was not seen with pre-treatment and post-treatment of the cells. Cell viability was also tested for, demonstrating that the presence of BRL aids cell survival. This work was then expanded out to Sindbis virus (SINV), and an Echovirus. The Echovirus served as a negative control due to its unenveloped nature. In both viruses, BRL was once again found to be effective at reducing viral titer.


This thesis has been embargoed for 2 years. It will be available for access in November 2023 at the earliest.


Brilacidin, Echovirus, Enveloped, Sindbis Virus, Rift Valley Fever Virus, Defensin mimetic