Ginkgolic Acid Inhibits Herpes Simplex Virus Type 1 Skin Infection and Prevents Zosteriform Spread in Mice
Herpes simplex virus type 1 (HSV-1) causes a lifelong latent infection with an estimated global prevalence of 66%. Primary and recurrent HSV infections are characterized by a tingling sensation, followed by an eruption of vesicles, which can cause painful erosions. Commonly used antiviral drugs agai...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-01-01
|
Series: | Viruses |
Subjects: | |
Online Access: | https://www.mdpi.com/1999-4915/13/1/86 |
id |
doaj-422602d3d3f644a6a0d2f0090d909ae0 |
---|---|
record_format |
Article |
spelling |
doaj-422602d3d3f644a6a0d2f0090d909ae02021-01-10T00:03:38ZengMDPI AGViruses1999-49152021-01-0113868610.3390/v13010086Ginkgolic Acid Inhibits Herpes Simplex Virus Type 1 Skin Infection and Prevents Zosteriform Spread in MiceMaimoona S. Bhutta0Oren Shechter1Elisa S. Gallo2Stephen D. Martin3Esther Jones4Gustavo F. Doncel5Ronen Borenstein6Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USADepartment of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USABoard-Certified Dermatologist and Independent Researcher, Norfolk, VA 23507, USADepartment of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USADepartment of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USACONRAD, Arlington, VA 22209, USADepartment of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USAHerpes simplex virus type 1 (HSV-1) causes a lifelong latent infection with an estimated global prevalence of 66%. Primary and recurrent HSV infections are characterized by a tingling sensation, followed by an eruption of vesicles, which can cause painful erosions. Commonly used antiviral drugs against HSV infection are nucleoside analogues including acyclovir (ACV), famciclovir, and valacyclovir. Although these nucleoside analogues reduce morbidity and mortality in immunocompetent individuals, ACV-resistant HSV strains (ACV<sup>R</sup>-HSV) have been isolated from immunocompromised patients. Thus, ACV<sup>R</sup>-HSV infection poses a critical emerging public health concern. Recently, we reported that ginkgolic acid (GA) inhibits HSV-1 by disrupting viral structure, blocking fusion, and inhibiting viral protein synthesis. Additionally, we showed GA affords a broad spectrum of fusion inhibition of all three classes of fusion proteins, including those of HIV, Ebola, influenza A and Epstein Barr viruses. Here we report GA’s antiviral activity against HSV-1 skin infection in BALB/cJ mice. GA-treated mice demonstrated a significantly reduced mortality rate and decreased infection scores compared to controls treated with dimethylsulfoxide (DMSO)-vehicle. Furthermore, GA efficiently inhibited ACV<sup>R</sup>-HSV-1 strain 17+ in vitro and in vivo. Since GA’s mechanism of action includes virucidal activity and fusion inhibition, it is expected to work alone or synergistically with other anti-viral drugs, and we anticipate it to be effective against additional cutaneous and potentially systemic viral infections.https://www.mdpi.com/1999-4915/13/1/86ginkgolic acidantiviralherpes simplex type 1acyclovir-resistancezosteriform infectionfusion inhibition |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maimoona S. Bhutta Oren Shechter Elisa S. Gallo Stephen D. Martin Esther Jones Gustavo F. Doncel Ronen Borenstein |
spellingShingle |
Maimoona S. Bhutta Oren Shechter Elisa S. Gallo Stephen D. Martin Esther Jones Gustavo F. Doncel Ronen Borenstein Ginkgolic Acid Inhibits Herpes Simplex Virus Type 1 Skin Infection and Prevents Zosteriform Spread in Mice Viruses ginkgolic acid antiviral herpes simplex type 1 acyclovir-resistance zosteriform infection fusion inhibition |
author_facet |
Maimoona S. Bhutta Oren Shechter Elisa S. Gallo Stephen D. Martin Esther Jones Gustavo F. Doncel Ronen Borenstein |
author_sort |
Maimoona S. Bhutta |
title |
Ginkgolic Acid Inhibits Herpes Simplex Virus Type 1 Skin Infection and Prevents Zosteriform Spread in Mice |
title_short |
Ginkgolic Acid Inhibits Herpes Simplex Virus Type 1 Skin Infection and Prevents Zosteriform Spread in Mice |
title_full |
Ginkgolic Acid Inhibits Herpes Simplex Virus Type 1 Skin Infection and Prevents Zosteriform Spread in Mice |
title_fullStr |
Ginkgolic Acid Inhibits Herpes Simplex Virus Type 1 Skin Infection and Prevents Zosteriform Spread in Mice |
title_full_unstemmed |
Ginkgolic Acid Inhibits Herpes Simplex Virus Type 1 Skin Infection and Prevents Zosteriform Spread in Mice |
title_sort |
ginkgolic acid inhibits herpes simplex virus type 1 skin infection and prevents zosteriform spread in mice |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2021-01-01 |
description |
Herpes simplex virus type 1 (HSV-1) causes a lifelong latent infection with an estimated global prevalence of 66%. Primary and recurrent HSV infections are characterized by a tingling sensation, followed by an eruption of vesicles, which can cause painful erosions. Commonly used antiviral drugs against HSV infection are nucleoside analogues including acyclovir (ACV), famciclovir, and valacyclovir. Although these nucleoside analogues reduce morbidity and mortality in immunocompetent individuals, ACV-resistant HSV strains (ACV<sup>R</sup>-HSV) have been isolated from immunocompromised patients. Thus, ACV<sup>R</sup>-HSV infection poses a critical emerging public health concern. Recently, we reported that ginkgolic acid (GA) inhibits HSV-1 by disrupting viral structure, blocking fusion, and inhibiting viral protein synthesis. Additionally, we showed GA affords a broad spectrum of fusion inhibition of all three classes of fusion proteins, including those of HIV, Ebola, influenza A and Epstein Barr viruses. Here we report GA’s antiviral activity against HSV-1 skin infection in BALB/cJ mice. GA-treated mice demonstrated a significantly reduced mortality rate and decreased infection scores compared to controls treated with dimethylsulfoxide (DMSO)-vehicle. Furthermore, GA efficiently inhibited ACV<sup>R</sup>-HSV-1 strain 17+ in vitro and in vivo. Since GA’s mechanism of action includes virucidal activity and fusion inhibition, it is expected to work alone or synergistically with other anti-viral drugs, and we anticipate it to be effective against additional cutaneous and potentially systemic viral infections. |
topic |
ginkgolic acid antiviral herpes simplex type 1 acyclovir-resistance zosteriform infection fusion inhibition |
url |
https://www.mdpi.com/1999-4915/13/1/86 |
work_keys_str_mv |
AT maimoonasbhutta ginkgolicacidinhibitsherpessimplexvirustype1skininfectionandpreventszosteriformspreadinmice AT orenshechter ginkgolicacidinhibitsherpessimplexvirustype1skininfectionandpreventszosteriformspreadinmice AT elisasgallo ginkgolicacidinhibitsherpessimplexvirustype1skininfectionandpreventszosteriformspreadinmice AT stephendmartin ginkgolicacidinhibitsherpessimplexvirustype1skininfectionandpreventszosteriformspreadinmice AT estherjones ginkgolicacidinhibitsherpessimplexvirustype1skininfectionandpreventszosteriformspreadinmice AT gustavofdoncel ginkgolicacidinhibitsherpessimplexvirustype1skininfectionandpreventszosteriformspreadinmice AT ronenborenstein ginkgolicacidinhibitsherpessimplexvirustype1skininfectionandpreventszosteriformspreadinmice |
_version_ |
1724343712998227968 |