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administered by vena caudalis route after infection. Two control groups were admin-
istered with 200 μl normal sodium (negative control) and penicillin (0.42 mg/kg/d,
positive control) respectively by the same injection route. Treatments were continued
3 times a day for 3 consecutive days, and these levels of chemicals caused few toxic
influences on normal mice. The results are expressed as cumulative survival rates over
the following 8-day observation.
CONCLUSION
To summarize, we have successfully found out several promising lead compounds for
further drug development in this study, which also can be used as inhibitors to explore
the mechanism of autophosphorylation by VicK as well as other HKs. Important work
in future would be validation of their antibacterial effects in different strains and struc-
tural modification for more effective derivatives with less in vivo toxicity, and inves-
tigation into whether they can bind to other ATP-dependent kinase is also necessary.
KEYWORDS
Autophosphorylation
Cytoplasmic portion
Cytotoxicity
Streptococcus pneumoniae
AUTHORS' CONTRIBUTIONS
Xuemei Zhang and Yibing Yin conceived of the study and participated in its design
and coordination. Nan Li, Fei Wang, and Weiliang Zhu carried out the modeling of
VicK protein and structure-based virtual screening. Nan Li, Siqiang Niu, Youqiang Li,
Kaifeng Wu, and Ju Cao participated in the biological experiments of the in vivo as-
says and the in vitro assays. Nan Li, Fei Wang, and Nanlin Yin participated in analyzed
the data and produced figures. Nan Li, Fei Wang, Weiliang Zhu, Xuemei Zhang and
Yibing Yin drafted the manuscript. All the authors have read and approved the final
manuscript.
ACKNOWLEDGMENTS
This work was supported by the National Natural Science Foundation of China (No.
30671868, 20721003).
 
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