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Article: Screening of an FDA-Approved Drug Library with a Two-Tier System Identifies an Entry Inhibitor of Severe Fever with Thrombocytopenia Syndrome Virus

TitleScreening of an FDA-Approved Drug Library with a Two-Tier System Identifies an Entry Inhibitor of Severe Fever with Thrombocytopenia Syndrome Virus
Authors
KeywordsAntiviral
Broxyquinoline
Bunyavirales
Eltrombopag
Entry
Issue Date2019
PublisherMolecular Diversity Preservation International (MDPI) AG.. The Journal's web site is located at http://www.mdpi.com/journal/viruses
Citation
Viruses, 2019, v. 11, p. 385 How to Cite?
AbstractSevere fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case-fatality rates of up to 30%. There are currently very limited treatment options for SFTSV infection. We conducted a drug repurposing program by establishing a two-tier test system to rapidly screen a Food and Drug Administration- (FDA)-approved drug library for drug compounds with anti-SFTSV activity in vitro. We identified five drug compounds that inhibited SFTSV replication at low micromolar concentrations, including hexachlorophene, triclosan, regorafenib, eltrombopag, and broxyquinoline. Among them, hexachlorophene was the most potent with an IC50 of 1.3 +/- 0.3 mu M and a selectivity index of 18.7. Mechanistic studies suggested that hexachlorophene was a virus entry inhibitor, which impaired SFTSV entry into host cells by interfering with cell membrane fusion. Molecular docking analysis predicted that the binding of hexachlorophene with the hydrophobic pocket between domain I and domain III of the SFTSV Gc glycoprotein was highly stable. The novel antiviral activity and mechanism of hexachlorophene in this study would facilitate the use of hexachlorophene as a lead compound to develop more entry inhibitors with higher anti-SFTSV potency and lower toxicity.
Persistent Identifierhttp://hdl.handle.net/10722/274572
ISSN
2017 Impact Factor: 3.761
2015 SCImago Journal Rankings: 1.873
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYuan, S-
dc.contributor.authorChan, JFW-
dc.contributor.authorYe, ZW-
dc.contributor.authorWen, L-
dc.contributor.authorTsang, TGW-
dc.contributor.authorCao, J-
dc.contributor.authorHuang, J-
dc.contributor.authorChan, CYC-
dc.contributor.authorChik, KKH-
dc.contributor.authorChoi, GKY-
dc.contributor.authorCai, J-
dc.contributor.authorYin, F-
dc.contributor.authorChu, H-
dc.contributor.authorLiang, M-
dc.contributor.authorJin, D-
dc.contributor.authorYuen, KY-
dc.date.accessioned2019-08-18T15:04:25Z-
dc.date.available2019-08-18T15:04:25Z-
dc.date.issued2019-
dc.identifier.citationViruses, 2019, v. 11, p. 385-
dc.identifier.issn1999-4915-
dc.identifier.urihttp://hdl.handle.net/10722/274572-
dc.description.abstractSevere fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case-fatality rates of up to 30%. There are currently very limited treatment options for SFTSV infection. We conducted a drug repurposing program by establishing a two-tier test system to rapidly screen a Food and Drug Administration- (FDA)-approved drug library for drug compounds with anti-SFTSV activity in vitro. We identified five drug compounds that inhibited SFTSV replication at low micromolar concentrations, including hexachlorophene, triclosan, regorafenib, eltrombopag, and broxyquinoline. Among them, hexachlorophene was the most potent with an IC50 of 1.3 +/- 0.3 mu M and a selectivity index of 18.7. Mechanistic studies suggested that hexachlorophene was a virus entry inhibitor, which impaired SFTSV entry into host cells by interfering with cell membrane fusion. Molecular docking analysis predicted that the binding of hexachlorophene with the hydrophobic pocket between domain I and domain III of the SFTSV Gc glycoprotein was highly stable. The novel antiviral activity and mechanism of hexachlorophene in this study would facilitate the use of hexachlorophene as a lead compound to develop more entry inhibitors with higher anti-SFTSV potency and lower toxicity.-
dc.languageeng-
dc.publisherMolecular Diversity Preservation International (MDPI) AG.. The Journal's web site is located at http://www.mdpi.com/journal/viruses-
dc.relation.ispartofViruses-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAntiviral-
dc.subjectBroxyquinoline-
dc.subjectBunyavirales-
dc.subjectEltrombopag-
dc.subjectEntry-
dc.titleScreening of an FDA-Approved Drug Library with a Two-Tier System Identifies an Entry Inhibitor of Severe Fever with Thrombocytopenia Syndrome Virus-
dc.typeArticle-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailCao, J: caojl@hku.hk-
dc.identifier.emailHuang, J: huangjj@hku.hk-
dc.identifier.emailChan, CYC: cyc415@hku.hk-
dc.identifier.emailCai, J: caijuice@hku.hk-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailJin, D: dyjin@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authorityJin, D=rp00452-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturepublished_or_final_version-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/v11040385-
dc.identifier.pmid31027241-
dc.identifier.scopuseid_2-s2.0-85065331478-
dc.identifier.hkuros301132-
dc.identifier.hkuros301649-
dc.identifier.volume11-
dc.identifier.spage385-
dc.identifier.epage385-
dc.identifier.isiWOS:000467310600082-
dc.publisher.placeSwitzerland-

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