Thymus capitatus flavonoids inhibit infection of Kaposi's sarcoma‐associated herpesvirus

Kaposi's sarcoma‐associated herpesvirus (KSHV), also known as human herpes virus 8 (HHV‐8), causes primary effusion lymphoma, multicentric Castleman's disease, and Kaposi's sarcoma. Few antiviral drugs are available to efficiently control KSHV infection, and therefore, the development of novel, effective anti‐KSHV treatments is needed. The aim of this study was to determine the antiviral activity of ethanolic and aqueous extracts, essential oils, and certain flavonoids (hesperidin, eupafolin, and vicenin) derived from Thymus capitatus (commonly known as thyme). We assessed the toxicity of these different extracts and components in RPE‐1 cell cultures using the MTS test and evaluated their antiviral effect using the TCID(50) method. The mechanism of action was determined through time‐of‐addition tests as well as viral entry, attachment, and virucidal assays. Additionally, western blot analysis was also used to assess their modes of action. Total treatment assay showed that the aqueous extract of T. capitatus has the highest inhibitory effect against KSHV(LYT) with an EC(50) value of 0.2388 µg·mL(−1). Both hesperidin and eupafolin showed the ability to inactivate viral infection in a dose–response manner (EC(50) values of 0.2399 and 1.396 µm, respectively). Moreover, they were able to inactivate KSHV(Lyt) postinfection by reducing viral protein expression. In summary, the effective antiviral property of the aqueous extract is likely a result of the inhibition of viral growth within the host cells by both hesperidin and eupafolin.