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Two-component systems (TCSs) are the major signal transduction pathways in bacteria and have emerged as potential targets for antibacterial drugs. Among the 13 pairs of TCSs proteins presenting in <jats:italic>S. pneumoniae<\/jats:italic>, VicR\/K is the unique one essential for bacterium growth, and block agents to which, if can be found, may be developed as effective antibiotics against <jats:italic>S. pneumoniae<\/jats:italic> infection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Using a structure-based virtual screening (SBVS) method, 105 compounds were computationally identified as potential inhibitors of the histidine kinase (HK) VicK protein from the compound library SPECS. Six of them were then validated <jats:italic>in vitro<\/jats:italic> to be active in inhibiting the growth of <jats:italic>S. pneumoniae<\/jats:italic> without obvious cytotoxicity to Vero cell. In mouse sepsis models, these compounds are still able to decrease the mortality of the mice infected by <jats:italic>S. pneumoniae<\/jats:italic> and one compound even has significant therapeutic effect.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>To our knowledge, these compounds are the first reported inhibitors of HK with antibacterial activity <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, and are novel lead structures for developing new drugs to combat pneumococcal infection.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2180-9-129","type":"journal-article","created":{"date-parts":[[2009,6,27]],"date-time":"2009-06-27T06:13:38Z","timestamp":1246083218000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Discovery of novel inhibitors of Streptococcus pneumoniae based on the virtual screening with the homology-modeled structure of histidine kinase (VicK)"],"prefix":"10.1186","volume":"9","author":[{"given":"Nan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqiang","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaifeng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youqiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanlin","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiliang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibing","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,6,27]]},"reference":[{"issue":"11","key":"800_CR1","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1007\/BF02005442","volume":"10","author":"GA Bruyn","year":"1991","unstructured":"Bruyn GA, van Furth R: Pneumococcal polysaccharide vaccines: indications, efficacy and recommendations. 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