Identification of novel small-molecular inhibitors of Staphylococcus aureus sortase A using hybrid virtual screening.
J Antibiot (Tokyo)
; 75(6): 321-332, 2022 06.
Article
in English
| MEDLINE | ID: covidwho-1878523
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 compound bound sortase A with KD value of 189 µM. 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Staphylococcal Infections
/
COVID-19
Limits:
Humans
Language:
English
Journal:
J Antibiot (Tokyo)
Year:
2022
Document Type:
Article
Affiliation country:
S41429-022-00524-8
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