Augmented antiviral activity of chlorhexidine gluconate on herpes simplex virus type 1, H1N1 influenza A virus, and adenovirus in combination with salicylic acid

Arch Virol. 2023 Nov 30;168(12):302. doi: 10.1007/s00705-023-05932-1.


Background: The excessive usage of chlorhexidine gluconate (CHG) as a broad-spectrum antimicrobial reagent can have a negative impact on the environment and on human health. The aim of this study was to investigate the effectiveness of some plant-derived compounds in reducing the CHG concentration required to exert its antiviral activity.

Methods: Antiviral assays were conducted according to EN 14476 (2019) against herpes simplex virus type 1 (HSV-1), H1N1 influenza A virus, and adenovirus type 5 (Ad-5) as enveloped and non-enveloped viral models to assess the synergistic interaction of CHG and natural additive compounds.

Results: The effective concentration of 0.247 mM CHG against HSV-1 was decreased tenfold in combination with 0.0125 mM salicylic acid, with a titer reduction of 1.47 ⋅ 104 CCID50/ml. The time required for complete inactivation of HSV-1 particles was reduced to 15 min when the virus was exposed to 0.061 mM CHG and 0.0125 mM salicylic acid. Additionally, the presence of salicylic acid protected the CHG activity against interfering substances.

Conclusion: Our supplemented CHG formulation showed immediate antiviral effectiveness, which is important for management of the infections. CHG can be combined with salicylic acid to exhibit synergistic antiviral activity at lower concentrations and reduce the time required for inactivation. Furthermore, in the presence of interfering substances, the combination has higher antiviral activity than CHG alone.

Keywords: Adenovirus type 5; Chlorhexidine gluconate; HSV-1; Influenza virus H1N1; Salicylic acid; Synergy.

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae Infections*
  • Anti-Infective Agents, Local*
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Herpesvirus 1, Human*
  • Humans
  • Influenza A Virus, H1N1 Subtype*
  • Salicylic Acid / pharmacology


  • chlorhexidine gluconate
  • Salicylic Acid
  • Antiviral Agents
  • Anti-Infective Agents, Local