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Exploring the Effectiveness of Acyclovir against Ranaviral Thymidine Kinases: Molecular Docking and Experimental
Richárd Rácz1, Ákos Gellért1, Tibor Papp1
1HUN-REN Veterinary Medical Research Institute, H-1143 Budapest, Hungary.
Abstract:
The effectiveness of acyclovir, a selective anti-herpesvirus agent, was tested both in silico and in vitro against two ranaviruses, namely the European catfish virus (ECV) and Frog virus 3 (FV3). ECV can cause significant losses in catfish aquaculture, while FV3 poses a risk to vulnerable amphibian populations. The genome of ranaviruses encodes thymidine kinases (TKs) similar to those of herpesviruses. Molecular docking simulations demonstrated that the acyclovir molecule can bind to the active sites of both investigated viral TKs in an orientation conducive to phosphorylation. Subsequently, the antiviral effect of acyclovir was tested in vitro in Epithelioma Papulosum Cyprini (EPC) cells with endpoint titration and qPCR. Acyclovir was used at a concentration of 800 µM, which significantly reduced the viral loads and titers of the ranaviruses. A similar reduction rate was observed with Ictalurid herpesvirus 2, which was used as a positive control virus. These promising results indicate that acyclovir might have a wider range of uses; besides its effectiveness against herpesviruses, it could also be used against ranavirus infections.
Insights
Acyclovir effectively reduced ranavirus infections in laboratory tests. This antiviral drug, typically used for herpesviruses, shows promise for treating European catfish virus and Frog virus 3.
Area of Science:
- Virology
- Molecular Biology
- Aquaculture
Background:
- Ranaviruses, such as European catfish virus (ECV) and Frog virus 3 (FV3), cause significant economic losses in aquaculture and pose threats to amphibian populations.
- Ranaviruses possess thymidine kinases (TKs) analogous to those found in herpesviruses, suggesting potential susceptibility to antiviral drugs targeting these enzymes.
Purpose of the Study:
- To investigate the in silico and in vitro efficacy of acyclovir, a known anti-herpesvirus agent, against ECV and FV3.
- To determine if acyclovir's mechanism of action, involving TK phosphorylation, is applicable to ranaviruses.
Main Methods:
- In silico molecular docking simulations to assess acyclovir binding to ranaviral TKs.
- In vitro antiviral assays using Epithelioma Papulosum Cyprini (EPC) cells, employing endpoint titration and quantitative PCR (qPCR) to measure viral loads.
- Utilized Ictalurid herpesvirus 2 as a positive control.
Main Results:
- Molecular docking confirmed acyclovir's ability to bind to the active sites of ECV and FV3 TKs.
- In vitro studies demonstrated that acyclovir (800 µM) significantly reduced viral loads and titers for both ECV and FV3.
- A comparable reduction was observed with the positive control, Ictalurid herpesvirus 2.
Conclusions:
- Acyclovir exhibits significant antiviral activity against ranaviruses (ECV and FV3) in vitro.
- The findings suggest that acyclovir's mechanism targeting viral thymidine kinases is effective against ranaviruses.
- Acyclovir represents a potential therapeutic agent for ranaviral infections, expanding its application beyond herpesviruses.
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