The therapeutic potential of thiocyanate and hypothiocyanous acid against pulmonary infections

Hypothiocyanous acid (HOSCN) is an endogenous oxidant produced by peroxidase oxidation of thiocyanate (SCN−), an ubiquitous sulfur-containing pseudohalide synthesized from cyanide. HOSCN serves as a potent microbicidal agent against pathogenic bacteria, viruses, and fungi, functioning through thiol-targeting mechanisms, independent of currently approved antimicrobials. Additionally, SCN− reacts with hypochlorous acid (HOCl), a highly reactive oxidant produced by myeloperoxidase (MPO) at sites of inflammation, also producing HOSCN. This imparts both antioxidant and antimicrobial potential to SCN−. In this review, we discuss roles of HOSCN/SCN− in immunity and potential therapeutic implications for combating infections. [Display omitted] •Hypothiocyanous acid (HOSCN) is an endogenous oxidant that demonstrates antimicrobial activities against viruses, bacteria and fungi.•Multiple preclinical studies reported benefits of promoting HOSCN formation in vivo to treat pulmonary infections.•HOSCN is better tolerated by mammalian cells than other chordata peroxidase-derived oxidants, such as hypochlorous acid.•Some bacterial strains are resistant to HOSCN, primarily via similar oxidoreductase mechanisms to those reported in mammalian cells.•HOSCN/SCN- treatment holds promise for viral, bacterial, and fungal infections, but potential toxicity and HOSCN resistance must be considered.