In vitro and silico studies of geraniin interfering with HSV-2 replication by targeting glycoprotein D

Abstract

Residues ASN94 and GLN41 presented the highest frequency in molecular docking tests. The geraniin-glycoprotein D(gD) complexes was stable with RMSD(root mean square deviation)value less than 0.3 nm. The Molecular dynamic (MD) simulations revealed stable hydrogen bonds between gD and geraniin. Root mean square fluctuation (RMSF) values were less than 0.15 nm around the interface of geraniin-gD complex. In virucidal assays showed a much higher anti-HSV-2 inhibition activity of geraniin as compared to acyclovir(ACV).Human immunodeficiency virus transactivator (HIV-TAT) treatment significantly enhanced HSV-2 replication and lethal effect on HaCaT cells. The inhibitory rate of geraniin against HSV-2 coinfected with HIV-TAT was significantly decreased. The immunofluorescence results also revealed that HSV-2 gD expression presented a green fluorescence on HaCaT cells membranes and showed clear downregulation in geraniin-treated cells, but was expressed clearly on cell membranes under geraniin, HSV-2 and HIV-TAT cotreatment. The anti-apoptotic effect from geraniin persisted after 72 h, while the anti-apoptotic effect from geraniin diminished when HIV-TAT and geraniin were combined.

Graphical Abstract

Keywords:

• Geraniin
• HSV-2
• molecular docking
• molecular dynamics
• membrane fusion

Acknowledgments

We are grateful to Prof. Qinxue Hu, China Institute of Virology, Wuhan, China.

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

The data supporting the findings of the article is available in Supporting Documents.

Additional information

Funding

The authors are very grateful for the support of the Wuxi Medical Development Discipline-Infectious Disease Development Discipline Fund (Grant no.FZXK006).