Antiviral activity of CAVAC-1901, a combination of 3 standardized medicinal plants, against highly pathogenic influenza A virus in chickens

Three different medicinal plants that consisted of the formulated mixture (CAVAC-1901) have been traditionally used for distinct medicinal purposes in different areas. Angelica dahurica has been used as an important ingredient of a prescription, Gumiganghwal-tang, for the common cold and influenza. Curcuma longa has been utilized for the treatment of asthma, and jaundice. Pinus densiflora (Korean red pine) has been used to improve memory and brain function for the treatment of vascular. Industrial livestock, which are characterized by dense breeding, are vulnerable to influenza infection, causing severe economic loss and social problems. However, there are no viable alternatives due to the risk of the occurrence of variants. Therefore, the aim of this study was to discover anti-influenza combinations of different medicinal plants with the concept of a multicomponent and multitarget (MCMT) strategy in traditional Chinese medicine (TCM). As part of a continuous project, 3 medicinal plants whose inhibitory activity against influenza A was previously reported at the compound level, and the inhibition of cytopathic effects (CPEs) by these formulated mixtures was evaluated against influenza A virus H1N1. A selected combination with an optimal ratio exhibiting synergistic activity was assessed for its antiviral activity in chickens against the highly pathogenic avian influenza (HPAI) H5N6. The selected combination (CAVAC-1901) showed potent inhibitory effects on the expression of neuraminidase and nucleoprotein, by RT-qPCR, Western blot, and immunofluorescence assays. The antiviral activity was more evident in chickens infected with H5N6. The sample-treated group (50 mg/kg/d) decreased mortality and virus titers in various organs. Our results indirectly suggest synergistic inhibitory activity of the combination of 3 different medicinal plants with different modes of action. Taken together, an optimally formulated mixture (CAVAC-1901) could serve as an effective alternative to current measures to minimize damage caused by HPAIs.