Identification of novel small-molecular inhibitors of Staphylococcus aureus sortase A using hybrid virtual screening
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Galyna P Volynets
- Fabian Barthels
- Stefan J Hammerschmidt
- Olena V Moshynets
- Sergiy S Lukashov
- Sergiy A Starosyla
- Hanna V Vyshniakova
- Olga S Iungin
- Volodymyr G Bdzhola
- Andrii O Prykhod'ko
- Anatolii R Syniugin
- Vladislav M Sapelkin
- Sergiy M Yarmoluk
- Tanja Schirmeister
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000784861300001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1038/s41429-022-00524-8
- eISSN
- 1881-1469
- Externe Identifier
- Clarivate Analytics Document Solution ID: 1A5EY
- PubMed Identifier: 35440771
- ISSN
- 0021-8820
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- JOURNAL OF ANTIBIOTICS
- Paginierung
- 321 - 332
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Titel
- Identification of novel small-molecular inhibitors of Staphylococcus aureus sortase A using hybrid virtual screening
- Sub types
- Article
- Ausgabe der Zeitschrift
- 75
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Galyna P Volynets
- Fabian Barthels
- Stefan J Hammerschmidt
- Olena V Moshynets
- Sergiy S Lukashov
- Sergiy A Starosyla
- Hanna V Vyshniakova
- Olga S Iungin
- Volodymyr G Bdzhola
- Andrii O Prykhod’ko
- Anatolii R Syniugin
- Vladislav M Sapelkin
- Sergiy M Yarmoluk
- Tanja Schirmeister
- DOI
- 10.1038/s41429-022-00524-8
- eISSN
- 1881-1469
- ISSN
- 0021-8820
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- The Journal of Antibiotics
- Sprache
- en
- Online publication date
- 2022
- Paginierung
- 321 - 332
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1038/s41429-022-00524-8
- Datum der Datenerfassung
- 2022
- Titel
- Identification of novel small-molecular inhibitors of Staphylococcus aureus sortase A using hybrid virtual screening
- Ausgabe der Zeitschrift
- 75
Data source: Crossref
- 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 IC<sub>50</sub> 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 K<sub>D</sub> 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.
- Addresses
- Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics, the NAS of Ukraine, 150 Zabolotnogo St, 03143, Kyiv, Ukraine. g.p.volynets@gmail.com.
- Autoren
- Galyna P Volynets
- Fabian Barthels
- Stefan J Hammerschmidt
- Olena V Moshynets
- Sergiy S Lukashov
- Sergiy A Starosyla
- Hanna V Vyshniakova
- Olga S Iungin
- Volodymyr G Bdzhola
- Andrii O Prykhod'ko
- Anatolii R Syniugin
- Vladislav M Sapelkin
- Sergiy M Yarmoluk
- Tanja Schirmeister
- DOI
- 10.1038/s41429-022-00524-8
- eISSN
- 1881-1469
- Externe Identifier
- PubMed Identifier: 35440771
- PubMed Central ID: PMC9016125
- Open access
- true
- ISSN
- 0021-8820
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- The Journal of antibiotics
- Schlüsselwörter
- Humans
- Biofilms
- Staphylococcus aureus
- Staphylococcal Infections
- Cysteine Endopeptidases
- Aminoacyltransferases
- Bacterial Proteins
- RNA, Viral
- Anti-Bacterial Agents
- Microbial Sensitivity Tests
- COVID-19
- SARS-CoV-2
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2022
- Open access status
- Open Access
- Paginierung
- 321 - 332
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum der Datenerfassung
- 2022
- Titel
- Identification of novel small-molecular inhibitors of Staphylococcus aureus sortase A using hybrid virtual screening.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 75
Files
https://www.nature.com/articles/s41429-022-00524-8.pdf https://europepmc.org/articles/PMC9016125?pdf=render
Data source: Europe PubMed Central
- 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.
- Date of acceptance
- 2022
- Autoren
- Galyna P Volynets
- Fabian Barthels
- Stefan J Hammerschmidt
- Olena V Moshynets
- Sergiy S Lukashov
- Sergiy A Starosyla
- Hanna V Vyshniakova
- Olga S Iungin
- Volodymyr G Bdzhola
- Andrii O Prykhod'ko
- Anatolii R Syniugin
- Vladislav M Sapelkin
- Sergiy M Yarmoluk
- Tanja Schirmeister
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/35440771
- DOI
- 10.1038/s41429-022-00524-8
- eISSN
- 1881-1469
- Externe Identifier
- PubMed Central ID: PMC9016125
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- J Antibiot (Tokyo)
- Schlüsselwörter
- Aminoacyltransferases
- Anti-Bacterial Agents
- Bacterial Proteins
- Biofilms
- COVID-19
- Cysteine Endopeptidases
- Humans
- Microbial Sensitivity Tests
- RNA, Viral
- SARS-CoV-2
- Staphylococcal Infections
- Staphylococcus aureus
- Sprache
- eng
- Country
- England
- Paginierung
- 321 - 332
- PII
- 10.1038/s41429-022-00524-8
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2022
- Titel
- Identification of novel small-molecular inhibitors of Staphylococcus aureus sortase A using hybrid virtual screening.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 75
Data source: PubMed
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