Structure-activity relationship of flavonoid bifunctional inhibitors against Zika virus infection

Min Zou; Hongmiao Liu; Jingyan Li; Xingang Yao; Yi Chen; Changwen Ke; Shuwen Liu

doi:10.1016/j.bcp.2020.113962

Structure-activity relationship of flavonoid bifunctional inhibitors against Zika virus infection

Biochem Pharmacol. 2020 Jul:177:113962. doi: 10.1016/j.bcp.2020.113962. Epub 2020 Apr 6.

Authors

Min Zou¹, Hongmiao Liu², Jingyan Li², Xingang Yao², Yi Chen², Changwen Ke³, Shuwen Liu⁴

Affiliations

¹ Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China. Electronic address: zoum2000@smu.edu.cn.
² Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
³ Guangdong Provincial Center for Disease Control and Prevention, Guangdong, China.
⁴ Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China. Electronic address: liusw@smu.edu.cn.

PMID: 32272109
DOI: 10.1016/j.bcp.2020.113962

Abstract

Zika virus (ZIKV) infection is a global public health problem due to its rapid spread and the possibility of causing microcephaly. Currently, no specific antivirals against ZIKV are available for treatment. In the present study, several flavonoids (galangin, kaempferide, quercetin, myricetin and EGCG) were found to reduce ZIKV induced plaques and viral RNA copies with negligible cytotoxic effects on host cells. In addition, inhibition of ZIKV propagation by flavonoids showed structure-activity relationship. Our results demonstrate flavonoids as inhibitors of ZIKV entry and NS2B-NS3 protease. Hence, these flavonoids could be used as potential bifunctional drugs for treating ZIKV infections.

Keywords: Antiviral; Entry inhibitors; Flavonoids; Protease; Zika virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Chlorocebus aethiops
Flavonoids / chemistry
Flavonoids / pharmacology*
Humans
Kaempferols / chemistry
Kaempferols / pharmacology
Molecular Structure
Quercetin / chemistry
Quercetin / pharmacology
Serine Endopeptidases / metabolism
Structure-Activity Relationship
Vero Cells
Viral Nonstructural Proteins / antagonists & inhibitors
Viral Nonstructural Proteins / metabolism
Viral Proteins / antagonists & inhibitors
Viral Proteins / metabolism
Virus Internalization / drug effects
Virus Replication / drug effects
Zika Virus / drug effects*
Zika Virus / genetics
Zika Virus / physiology
Zika Virus Infection / prevention & control*
Zika Virus Infection / virology

Substances

Antiviral Agents
Flavonoids
Kaempferols
NS2B protein, flavivirus
Viral Nonstructural Proteins
Viral Proteins
galangin
kaempferide
myricetin
Quercetin
NS3 protein, zika virus
Serine Endopeptidases