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.

Life (Basel, Switzerland)
|September 28, 2024
PubMed

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.