Synthesis and evaluation of 1,2,3-dithiazole inhibitors of the nucleocapsid protein of feline immunodeficiency virus (FIV) as a model for HIV infection

Abstract

We disclose a series of potent anti-viral 1,2,3-dithiazoles, accessed through a succinct synthetic approach from 4,5-dichloro-1,2,3-dithiazolium chloride (Appel's salt). A series of small libraries of compounds were screened against feline immunodeficiency virus (FIV) infected cells as a model for HIV. This approach highlighted new structure activity relationship understanding and led to the development of sub-micro molar anti-viral compounds with reduced toxicity. In addition, insight into the mechanistic progress of this system is provided via advanced QM-MM modelling. The 1,2,3-dithiazole represents a versatile scaffold with potential for further development to treat both FIV and HIV.

Keywords: 1,2,3-Dithiazoles; Feline Immunodeficiency Virus (FIV); Human Immunodeficiency Virus (HIV); Nucleocapsid protein; Zinc ejection.