Parvaneh Mehrbod - Department of Veterinary Tropical Diseases, University of Pretoria, Pretoria, South Africa
Fatemeh Fotouhi - Influenza and Another Respiratory Viruses Department, Pasteur Institute of IRAN, Tehran, Iran
Jacobus Nicolaas Eloff - Phytomedicine Programme, Department of Paraclinical Sciences, University of Pretoria, Pretoria, South Africa
Folorunso Oludayo Fasina - ECTAD, Food and Agriculture Organization of the United Nations (FAO), Dar es Salaam, Tanzania
Lyndy J. McGaw - Phytomedicine Programme, Department of Paraclinical Sciences, University of Pretoria, Pretoria, South Africa

Introduction and Objectives: Influenza A virus (IAV) is still a threat for human and animal health. The clinical manifestations of this infection are related to immune dysregulation, which causes serious risk factor for morbidity and mortality. The usage of traditional medication with immunomodulatory properties against influenza infection has been increased recently. Our previous study has shown the antiviral activity of quercetin-3-O-α-L-rhamnopyranoside (Q3R) isolated from Rapanea melanophloeos (RM) (L.) Mez (family Myrsinaceae) against H1N1 (A/PR/8/34) infection. This study aimed to confirm the immunomodulatory effect of Q3R on selective pro- and anti-inflammatory cytokines against IAV in vitro, also, to evaluate the physical interaction of Q3R with virus glycoproteins using computational docking. Materials and Methods: The MDCK cells were exposed to the Q3R and 100CCID50/100μl of H1N1 in combined treatments (co-, pre- and post-penetration treatments). Cell-free supernatants treated for 48 hr were collected and stored at -80°C until further processing. TNF-α, IL-6 and CCL-2 as pro-inflammatory cytokines and IL-27 and IFN-β as anti-inflammatory cytokines were measured by ELISA. Computational molecular docking as a virtual screen of the potential anti-influenza activity of Q3R was also performed. Results: The expression of cytokines proteins was significantly affected by Q3R treatment. It was shown that Q3R was much more effective against IAV when it was applied in co-penetration treatment. The molecular docking results showed the strong binding ability of Q3R with neuraminidase/hemagglutinin from H1N1 (A/PR/8/34). Conclusion: Quercetin-3-O-α-L-rhamnopyranoside was significantly effective against influenza infection outcome by immunomodulatory properties and binding ability to the viral receptors. Further research will focus on detecting the detailed specific mechanism of Q3R in virus-host interactions.

Influenza A virus, Quercetin-3-O-α-L-rhamnopyranoside, Cytokine, Molecular docking