Melaleuca alternifolia concentrate inhibits in vitro entry of influenza virus into host cells

Abstract

Influenza virus causes high morbidity among the infected population annually and occasionally the spread of pandemics. Melaleuca alternifolia Concentrate (MAC) is an essential oil derived from a native Australian tea tree. Our aim was to investigate whether MAC has any in vitro inhibitory effect on influenza virus infection and what mechanism does the MAC use to fight the virus infection. In this study, the antiviral activity of MAC was examined by its inhibition of cytopathic effects. In silico prediction was performed to evaluate the interaction between MAC and the viral haemagglutinin. We found that when the influenza virus was incubated with 0.010% MAC for one hour, no cytopathic effect on MDCK cells was found after the virus infection and no immunofluorescence signal was detected in the host cells. Electron microscopy showed that the virus treated with MAC retained its structural integrity. By computational simulations, we found that terpinen-4-ol, which is the major bioactive component of MAC, could combine with the membrane fusion site of haemagglutinin. Thus, we proved that MAC could prevent influenza virus from entering the host cells by disturbing the normal viral membrane fusion procedure.

Figure 1

Effects of MAC on the MDCK cell viability.

Figure 2

Protection efficacy by MAC against 2009 H1N1 virus infection to MDCK cell.

Figure 3

Treatment with MAC prevents the influenza virus entering the host cell.

Figure 4

The role of MAC on destroying the structural integrity of the virion.

Figure 5

(A) The structures of complex obtained from docking calculations. (B) RMSDs of terpinen-4-ol-HA complex compared to their original conformations as a function of time.

Figure 6

(A) Hydrogen bonds formed between terpinen-4-ol and residues in binding pocket. (B) The time dependent distance of terpinen-4-ol _I-56 (red) and terpinen-4-ol_N-60 (black).