The 8-bromobaicalein inhibited the replication of dengue, and Zika viruses and targeted the dengue polymerase

被引：6

作者：

Boonyasuppayakorn, Siwaporn ^{[1
]}

Saelee, Thanaphon ^{[1
]}

Huynh, Thao Nguyen Thanh ^{[2
]}

Hairani, Rita ^{[2
]}

Hengphasatporn, Kowit ^{[3
]}

Loeanurit, Naphat ^{[1
,4
]}

Cao, Van ^{[1
,4
]}

Vibulakhaophan, Vipanee ^{[1
,5
]}

Siripitakpong, Panattida ^{[6
]}

Kaur, Parveen ^{[7
]}

Chu, Justin Jang Hann ^{[7
,8
,9
,10
]}

Tunghirun, Chairat ^{[11
]}

Choksupmanee, Opas ^{[11
]}

Chimnaronk, Sarin ^{[8
]}

Shigeta, Yasuteru ^{[3
]}

Rungrotmongkol, Thanyada ^{[6
,12
]}

Chavasiri, Warinthorn ^{[2
]}

机构：

[1] Chulalongkorn Univ, Fac Med, Ctr Excellence Appl Med Virol, Dept Microbiol, Bangkok 10330, Thailand

[2] Chulalongkorn Univ, Fac Sci, Ctr Excellence Nat Prod Chem, Dept Chem, Bangkok 10330, Thailand

[3] Univ Tsukuba, Ctr Computat Sci, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058577, Japan

[4] Chulalongkorn Univ, Grad Sch, Interdisciplinary Program Microbiol, Bangkok 10330, Thailand

[5] Chulalongkorn Univ, Fac Sci, Dept Biol, Bangkok 10330, Thailand

[6] Chulalongkorn Univ, Fac Sci, Ctr Excellence Biocatalyst & Sustainable Biotechno, Dept Biochem, Bangkok 10330, Thailand

[7] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol & Immunol, Singapore 117545, Singapore

[8] Natl Univ Singapore, Yong Loo Lin Sch Med, Infect Dis Translat Res Programme, Singapore, Singapore

[9] Natl Univ Singapore, Yong Loo Lin Sch Med, NUS Med BSL3 Core Facil, Singapore, Singapore

[10] ASTAR, Inst Mol & Cell Biol IMCB, Singapore, Singapore

[11] Mahidol Univ, Inst Mol Biosci, Lab RNA Biol, Salaya Campus, Nakhon Pathom 73170, Thailand

[12] Chulalongkorn Univ, Fac Sci, Program Bioinformat & Computat Biol, Bangkok 10330, Thailand

来源：

SCIENTIFIC REPORTS | 2023年 / 13卷 / 01期

关键词：

DEPENDENT RNA-POLYMERASE; ANTIVIRAL ACTIVITY; NONCOMPETITIVE INHIBITORS; BAICALEIN; PROTEASE; TYPE-2; FLAVONOIDS; SEROTYPE-2; DISCOVERY; COMPLEX;

D O I：

10.1038/s41598-023-32049-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Dengue and Zika viruses are mosquito-borne flaviviruses burdening millions every year with hemorrhagic fever and neurological symptoms. Baicalein was previously reported as a potential anti-flaviviral candidate and halogenation of flavones and flavanones potentiated their antiviral efficacies. Here, we reported that a chemically modified 8-bromobaicalein effectively inhibited all dengue serotypes and Zika viruses at 0.66-0.88 micromolar in cell-based system. The compound bound to dengue serotype 2 conserved pocket and inhibited the dengue RdRp activity with 6.93 fold more than the original baicalein. Moreover, the compound was mildly toxic against infant and adult C57BL/6 mice despite administering continuously for 7 days. Therefore, the 8-bromobaicalein should be investigated further in pharmacokinetics and efficacy in an animal model.

引用

页数：13

共 67 条

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