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ABOUT News and Events Identification of novel small-molecular inhibitors of Staphylococcus aureus sortase A using hybrid virtual screening

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

Recently, the article dedicated to the development of Staphylococcus aureus sortase A inhibitors using the methods of molecular docking and pharmacophore screening has been published.

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-bonzoylamino)-benzoic acid which was able to inhibit S. aureus sortase A at the IC50 value of 59.7 mM. 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 compound bound sortase A with KD value of 189 mM. Antibacterial and antibiofilm assays also confirmed high specificity of the hit compound against two standard and three wild-type, S. aureus hospital infection isolates. The effect of the compound on biofilms produced by two S. aureus ATCC strains was also observed suggesting that the compound reduced biofilm formation by changing the biofilm structure and thickness.

  • Identification of novel small-molecular inhibitors of Staphylococcus aureus sortase A using hybrid virtual screening. Volynets GP, Barthels F, Hammerschmidt SJ, Moshynets OV, Lukashov SS, Starosyla SA, Vyshniakova HV, Iungin OS, Bdzhola VG, Prykhod'ko AO, Syniugin AR, Sapelkin VM, Yarmoluk SM, Schirmeister T. The Journal of Antibiotics. 2022,  75: 321-332.

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