Antiviral Activity of an Ethanolic Extract of Cinnamomum cassia and Cinnamaldehyde Against the Herpesviruses HSV-1 and VZV

Herpes simplex virus type 1 (HSV-1) and varicella–zoster virus (VZV) are clinically important alphaherpesviruses that establish lifelong latent infections and remain significant causes of morbidity despite the availability of antiviral drugs. The emergence of drug resistance and the inability of current therapies to eliminate latent virus reservoirs underscore the need for novel antiviral agents with alternative mechanisms of action. In the present study, we evaluated the antiviral activity of an ethanolic extract prepared from commercial cinnamon bark marketed as Cinnamomum cassia and cinnamaldehyde, a well-known constituent of cinnamon tested here as a purified compound, against HSV-1 and VZV in vitro. Antiviral activity was assessed using plaque reduction assays, time-of-addition experiments, and quantitative real-time PCR for viral DNA accumulation and specific viral immediate-early transcript levels. Both the C. cassia extract and cinnamaldehyde inhibited HSV-1 and VZV replication in a dose-dependent manner while exhibiting relatively low cytotoxicity. Nonlinear dose–response analysis yielded IC50 values of 3.44 and 2.80 µg/mL for the C. cassia extract against HSV-1 and VZV, respectively, and 0.961 and 1.50 µg/mL for cinnamaldehyde. Time-of-addition experiments demonstrated that antiviral activity was greatest when treatment was maintained throughout infection or initiated after viral entry, whereas pretreatment of cells or direct incubation with virus particles produced minimal effects. Both agents markedly reduced intracellular production of infectious progeny viruses and decreased viral DNA accumulation and the abundance of the specific immediate-early transcripts examined. These findings support a predominantly post-entry antiviral effect of both materials, rather than a primary effect on viral attachment or direct virion inactivation. Collectively, these results support further investigation of these agents as promising natural inhibitors of HSV and VZV infections.