VCOM Research Day Program Book 2023

Graduate Student Research Biomedical

05 Anti-Inflammatory FDA-Approved Drug, Auranofin, Exhibits Antibacterial Activity In Vitro And In Vivo Against Neisseria Gonorrhoeae

Hsin-Wen Liang 1 ; Ahmed E.M. Elhassanny 1 ; Nader S. Abutaleb 1 ; Mohamed N. Seleem 1 Corresponding author: hwliang@vt.edu

1 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University

screening with significant anti-gonoccocal activity. The activity of these compounds was tested against multidrug-resistant N. gonorrhoeae clinical isolates. The minimal inhibitory concentrations (MICs) of these nine compounds are ranging from 0.03 to 8 µg/ml. One of the drugs, anti-inflammatory drug auranofin, that showed potent activity (0.06 µg/ml) was further investigated. A time-kill kinetics assay revealed that auranofin exhibited rapid bactericidal activity in vitro against N. gonorrhoeae . Additionally, auranofin cleared the N. gonorrhoeae number in vitro in four hours, which is outperform to the drug of choice azithromycin. Moreover, auranofin reduced the N. gonorrhoeae burden in a female murine model of

vaginal infection by 1.04 (91%) and 1.40 (96%) log 10 after three and five days of treatment respectively. In conclusion, drug repurposing is a productive approach for drug discovery. The findings from this study provide the foundation for future gonorrhea therapeutics research.

Neisseria gonorrhoeae , the second most common bacterial cause of sexually transmitted infections (STIs), is listed as an urgent-threat pathogen by the Centers for Disease Control and Prevention (CDC). Due to the growing prevalence of resistance development against first-line treatment and several classes of antibiotics, the discovery of new anti gonorrhea therapeutics is an urgent need. Drug repurposing significantly reduces the time and expense of traditional drug development. In this study, we utilized a drug repurposing approach and screened 3,802 FDA-approved and clinical drugs against Neisseria gonorrhoeae FA1090. A total of nine novel non-antibiotic compounds were identified in the

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