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Identifying HSV-1 Inhibitors from Natural Compounds via Virtual Screening Targeting Surface Glycoprotein D
Jiadai Wu1,2,3, Helen Power1,2,4, Monica Miranda-Saksena3
1School of Chemical and Biomolecular Engineering, Faculty of Engineering, The University of Sydney, Sydney 2006, Australia.
Pharmaceuticals (Basel, Switzerland)
|March 26, 2022
Summary
This study used computational methods to screen over 500,000 natural compounds for new herpes simplex virus (HSV) treatments. Two compounds showed antiviral activity, with one demonstrating a novel mechanism of action against HSV.
Area of Science:
- Virology
- Computational Chemistry
- Drug Discovery
Background:
- Herpes simplex virus (HSV) infections pose a global health challenge requiring novel therapeutic strategies.
- Existing antiherpetic drugs face limitations, necessitating the identification of agents with distinct mechanisms of action for synergistic effects.
Purpose of the Study:
- To identify novel antiviral compounds targeting herpes simplex virus (HSV) using a structure-based molecular docking approach.
- To discover agents with potentially new mechanisms of action that could complement current therapies.
Main Methods:
- Virtual screening of over 527,000 natural compounds against the binding interfaces of HSV glycoprotein D (gD) using molecular docking.
- Filtering compounds for favorable Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiles.
- Experimental evaluation of top-ranked compounds in VERO cells.
Main Results:
- Two compounds exhibited potential antiherpetic activity.
- One compound demonstrated weak but significant antiviral activity against HSV, acting via viral inactivation in a dose-dependent manner.
- The identified compound's mechanism appears distinct from current antiherpetic agents like acyclovir.
Conclusions:
- In silico approaches are effective for discovering novel antiviral compounds.
- The identified compound warrants further investigation and optimization through medicinal chemistry for potential development as an antiherpetic agent.
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