Ginkgolic acid inhibits fusion of enveloped viruses

Sci Rep. 2020 Mar 16;10(1):4746. doi: 10.1038/s41598-020-61700-0.


Ginkgolic acids (GA) are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. GA has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated proteins through AMPK activation; and potential rescue of amyloid-β (Aβ) induced synaptic impairment. GA was also reported to have activity against Escherichia coli and Staphylococcus aureus. Several mechanisms for this activity have been suggested including: SUMOylation inhibition; blocking formation of the E1-SUMO intermediate; inhibition of fatty acid synthase; non-specific SIRT inhibition; and activation of protein phosphatase type-2C. Here we report that GA inhibits Herpes simplex virus type 1 (HSV-1) by inhibition of both fusion and viral protein synthesis. Additionally, we report that GA inhibits human cytomegalovirus (HCMV) genome replication and Zika virus (ZIKV) infection of normal human astrocytes (NHA). We show a broad spectrum of fusion inhibition by GA of all three classes of fusion proteins including HIV, Ebola virus (EBOV), influenza A virus (IAV) and Epstein Barr virus (EBV). In addition, we show inhibition of a non-enveloped adenovirus. Our experiments suggest that GA inhibits virion entry by blocking the initial fusion event. Data showing inhibition of HSV-1 and CMV replication, when GA is administered post-infection, suggest a possible secondary mechanism targeting protein and DNA synthesis. Thus, in light of the strong effect of GA on viral infection, even after the infection begins, it may potentially be used to treat acute infections (e.g. Coronavirus, EBOV, ZIKV, IAV and measles), and also topically for the successful treatment of active lesions (e.g. HSV-1, HSV-2 and varicella-zoster virus (VZV)).

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Astrocytes / metabolism
  • Chlorocebus aethiops
  • DNA Replication / drug effects
  • DNA Virus Infections / metabolism*
  • DNA Virus Infections / virology
  • DNA Viruses / drug effects*
  • DNA Viruses / genetics
  • DNA, Viral / genetics
  • HEK293 Cells
  • Humans
  • RNA Virus Infections / metabolism*
  • RNA Virus Infections / virology
  • RNA Viruses / drug effects*
  • RNA Viruses / genetics
  • Salicylates / pharmacology*
  • Vero Cells
  • Viral Envelope Proteins / antagonists & inhibitors*
  • Viral Envelope Proteins / biosynthesis
  • Viral Fusion Proteins / antagonists & inhibitors*
  • Viral Fusion Proteins / biosynthesis
  • Virion / drug effects
  • Virus Internalization / drug effects
  • Virus Replication / drug effects


  • Antiviral Agents
  • DNA, Viral
  • Salicylates
  • Viral Envelope Proteins
  • Viral Fusion Proteins
  • ginkgolic acid