Original Paper Intervirology 2018;61:14–22 Parthenolide Influences Herpes simplex virus 1 Replication in vitro Érica Benassi-Zanqueta a Caroline Fernandes Marques b Samara Requena Nocchi a, b Benedito Prado Dias Filho a, b Celso Vataru Nakamura a Tania Ueda-Nakamura a, b a Postgraduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Brazil; b Department of Basic Health Sciences, State University of Maringá, Maringá, Brazil Received: June 13, 2017 Accepted: May 14, 2018 Published online: July 12, 2018 Tania Ueda-Nakamura Department of Basic Health Sciences, State University of Maringá Av. Colombo 5790 Maringá, PR 87020-900 (Brazil) E-Mail tunakamura @uem.br © 2018 S. Karger AG, Basel E-Mail karger@karger.com www.karger.com/int DOI: 10.1159/000490055 Keywords Caspase · Herpes simplex virus 1 · Mitogen-activated protein kinase · NF-κB · Parthenolide Abstract Background/Aims: Parthenolide is a sesquiterpene lactone that is present in plants of the Tanacetum genus, for which many biological effects have already been reported, includ- ing antiherpetic activity. Although the effectiveness of par- thenolide against Herpes simplex virus 1 (HSV-1) has already been demonstrated, such findings are still controversial. The objective of this study was to investigate the ways in which parthenolide exerts anti-HSV-1 activity. Methods: The cyto- toxicity and antiviral activity of parthenolide were deter- mined by the MTT method and plaque reduction assay, re- spectively. The expression of cell and viral proteins during the treatment of infected cells was investigated by Western blot. Results: Both strains of HSV-1 were sensitive to parthe- nolide, and parthenolide was active only after penetration of the virus into the host cell. The expression of p65 protein decreased, the expression of caspases 8 and 9 increased, and the expression of c-Jun N-terminal kinase (JNK) and p38 pro- tein was altered in infected cells after parthenolide treat- ment, resulting in lower cell survival. The low expression of viral proteins gB, gD, and ICP0 confirmed the reduction of HSV-1 particle production. Conclusion: Parthenolide exerts anti-HSV-1 activity by impairing cell viability, which conse- quently interferes with the efficient infection and produc- tion of new viral particles. © 2018 S. Karger AG, Basel Introduction Herpes simplex virus 1 (HSV-1) is a DNA virus that is protected by an enveloped icosahedral capsid that causes latent infection. An estimated 60–80% of the world’s pop- ulation carry the virus, regardless of whether they mani- fest recurring symptoms [1]. The treatment of choice for HSV-1 is the use of nucleoside analogs that modulate the enzymatic activity necessary for the multiplication of vi- ral genetic material. Mutations, insertions, or deletions of the HSV-1 genome can lead to resistance, which can be problematic for immunocompromised patients, the el- derly, and patients with recurrent infection [2]. The