Glycosylated diphyllin as a broad-spectrum antiviral agent against Zika virus

Alicia Martinez-Lopez, Mirjana Persaud, Maritza Puray Chavez, Hongjie Zhang, Lijun Rong, Shufeng Liu, Tony T. Wang, Stefan G. Sarafianos, Felipe Diaz-Griffero

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Flaviviruses such as Zika cause sporadic pandemic outbreaks worldwide. There is an urgent need for anti-Zika virus (ZIKV) drugs to prevent mother-to-child transmission of ZIKV, new infections in high-risk populations, and the infection of medical personnel in ZIKV-affected areas. Methods: Here, we showed that the small molecule 6-deoxyglucose-diphyllin (DGP) exhibited anti-ZIKV activity both in vitro and in vivo. DGP potently blocked ZIKV infection across all human and monkey cell lines tested. DGP also displayed broad-spectrum antiviral activity against other flaviviruses. Remarkably, DGP prevented ZIKV-induced mortality in mice lacking the type I interferon receptor (Ifnar1−/−). Cellular and virological experiments showed that DGP blocked ZIKV at a pre-fusion step or during fusion, which prevented the delivery of viral contents into the cytosol of the target cell. Mechanistic studies revealed that DGP prevented the acidification of endosomal/lysosomal compartments in target cells, thus inhibiting ZIKV fusion with cellular membranes and infection. Findings: These investigations revealed that DGP inhibits ZIKV infection in vitro and in vivo. Interpretation: The small molecule DGP has great potential for preclinical studies and the ability to inhibit ZIKV infection in humans.

Original languageEnglish (US)
Pages (from-to)269-283
Number of pages15
JournalEBioMedicine
Volume47
DOIs
StatePublished - Sep 1 2019

Fingerprint

Viruses
Antiviral Agents
Flavivirus
Interferon alpha-beta Receptor
Fusion reactions
Aptitude
Pandemics
Infection
Cytosol
Haplorhini
Disease Outbreaks
diphyllin
Zika Virus
Mothers
Molecules
Acidification
Cell Line
Membranes
Mortality
Zika Virus Infection

Keywords

  • Endosomal
  • Fusion
  • Glycosylated diphyllin
  • Ifnar1
  • pH
  • Zika

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Glycosylated diphyllin as a broad-spectrum antiviral agent against Zika virus. / Martinez-Lopez, Alicia; Persaud, Mirjana; Chavez, Maritza Puray; Zhang, Hongjie; Rong, Lijun; Liu, Shufeng; Wang, Tony T.; Sarafianos, Stefan G.; Diaz-Griffero, Felipe.

In: EBioMedicine, Vol. 47, 01.09.2019, p. 269-283.

Research output: Contribution to journalArticle

Martinez-Lopez, A, Persaud, M, Chavez, MP, Zhang, H, Rong, L, Liu, S, Wang, TT, Sarafianos, SG & Diaz-Griffero, F 2019, 'Glycosylated diphyllin as a broad-spectrum antiviral agent against Zika virus', EBioMedicine, vol. 47, pp. 269-283. https://doi.org/10.1016/j.ebiom.2019.08.060
Martinez-Lopez A, Persaud M, Chavez MP, Zhang H, Rong L, Liu S et al. Glycosylated diphyllin as a broad-spectrum antiviral agent against Zika virus. EBioMedicine. 2019 Sep 1;47:269-283. https://doi.org/10.1016/j.ebiom.2019.08.060
Martinez-Lopez, Alicia ; Persaud, Mirjana ; Chavez, Maritza Puray ; Zhang, Hongjie ; Rong, Lijun ; Liu, Shufeng ; Wang, Tony T. ; Sarafianos, Stefan G. ; Diaz-Griffero, Felipe. / Glycosylated diphyllin as a broad-spectrum antiviral agent against Zika virus. In: EBioMedicine. 2019 ; Vol. 47. pp. 269-283.
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