Antiviral Activity of Rosemary Extract Against Zika Virus in Human Dermal Fibroblasts

Flaviviruses have increasingly emerged and re-emerged in recent decades, infecting millions of people annually. Zika virus is particularly concerning due to its associated pathological complications, including microcephaly in newborns and Guillain-Barré syndrome in adults, posing a significant threat to public health. Despite efforts made by the scientific community, no licensed drugs against flaviviruses have been developed. Medicinal plants show promise as a novel source of antiviral agents, as they possess a diverse array of biologically active secondary metabolites, making them potential candidates for therapeutic use. We sought to investigate the antiviral potential of rosemary extract (RE) against ZIKV in human dermal fibroblasts (HFF-1 cells), one of the earliest targets of infection. ZIKV was treated with various concentrations of RE or its individual major polyphenols, including rosmarinic acid (RA), carnosic acid (CA), and carnosol (CO), and the remaining infectivity of each sample was measured by plaque reduction assay. To evaluate the impact of RE on different stages of the ZIKV replication cycle, HFF-1 cells were treated before, during, and after infection, or the virus was treated before infection. RE exerted potent antiviral activity against ZIKV in both Vero and HFF-1 cells by directly acting on virus particles before infection. Importantly, RE significantly inhibited the later stages of the virus replication cycle by interfering with post-entry mechanisms within the host cell. Moreover, major RE-derived polyphenols CA and CO, but not RA, were shown to significantly reduce ZIKV infectivity. Overall, RE significantly impairs ZIKV infection in vitro by directly interacting with virus particles prior to adsorption and interfering with post-entry processes of the ZIKV replication cycle. This study provides rigorous evidence indicating the potential development of RE as an antiviral agent, warranting further investigation into the mechanisms underlying its inhibitory activity against ZIKV and its effects on other medically important flaviviruses.