Identification of novel small-molecular inhibitors of Staphylococcus aureus sortase A using hybrid virtual screening.

ABSTRACT: Staphylococcus aureus is one of the most dangerous pathogens commonly associated with high levels of morbidity and mortality. Sortase A is considered as a promising molecular target for the development of antistaphylococcal agents. Using hybrid virtual screening approach and FRET analysis, we have identified five compounds able to decrease the activity of sortase A by more than 50% at the concentration of 200 µM. The most promising compound was 2-(2-amino-3-chloro-benzoylamino)-benzoic acid which was able to inhibit S. aureus sortase A at the IC₅₀ value of 59.7 µM. This compound was selective toward sortase A compared to other four cysteine proteases - cathepsin L, cathepsin B, rhodesain, and the SARS-CoV2 main protease. Microscale thermophoresis experiments confirmed that this

SUBMITTER: Volynets GP 

PROVIDER: S-EPMC9016125 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature