The Cranberry Extract Oximacro ® Exerts in vitro Virucidal Activity Against Influenza Virus by Interfering With Hemagglutinin

• Published in: Frontiers in microbiology Vol. 9; p. 1826
• Main Authors: Luganini, Anna, Terlizzi, Maria E, Catucci, Gianluca, Gilardi, Gianfranco, Maffei, Massimo E, Gribaudo, Giorgio
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 07-08-2018
• Subjects: cranberry extract; dimeric A-type proanthocyanidins; hemagglutinin; influenza virus; Microbiology; Oximacro; PAC-A2; dimeric A-type proanthocyanidins; antiviral and virucidal activities; hemagglutinin; influenza virus; PAC-A2; cranberry extract; Oximacro
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2018.01826

The defense against influenza virus (IV) infections still poses a series of challenges. The current antiviral arsenal against influenza viruses is in fact limited; therefore, the development of new anti-influenza strategies effective against antigenically different viruses is an urgent priority. Bioactive compounds derived from medicinal plants and fruits may provide a natural source of candidates for such broad-spectrum antivirals. In this regard, cranberry (
Aiton) extracts on the basis of their recognized anti-adhesive activities against bacteria, may provide potential compounds able to prevent viral attachment to target cells. Nevertheless, only few studies have so far investigated the possible use of cranberry extracts as an antiviral tool. This study focuses on the suitability of a cranberry extract as a direct-acting anti-influenza compound. We show that the novel cranberry extract Oximacro
inhibits influenza A and B viruses (IAV, IBV) replication
because of its high content of A-type proanthocyanidins (PAC-A) dimers and trimers. Mechanistic studies revealed that Oximacro
prevents attachment and entry of IAV and IBV into target cells and exerts a virucidal activity. Oximacro
was observed to interact with the ectodomain of viral hemagglutinin (HA) glycoprotein, thus suggesting the interference with HA functions and a consequent loss of infectivity of IV particles. Fluorescence spectroscopy revealed a reduction in the intrinsic fluorescence of HA protein after incubation with purified dimeric PAC-A (PAC-A2), thus confirming a direct interaction between HA and Oximacro
PAC-A2.
docking simulations further supported the
results and indicated that among the different components of the Oximacro
chemical profile, PAC-A2 exhibited the best binding propensity with an affinity below 10 nM. The role of PAC-A2 in the anti-IV activity of Oximacro
was eventually confirmed by the observation that it prevented IAV and IVB replication and caused the loss of infectivity of IV particles, thus indicating PAC-A2 as the major active component of Oximacro
. As a whole, these results suggest Oximacro
as a potential candidate to create novel antiviral agents of natural origin for the prevention of IV infections.