Antiviral activity of Embelia ribes Burm. f. against influenza virus in vitro.

Arch Virol. 2018 Apr 10. doi: 10.1007/s00705-018-3842-6. [Epub ahead of print] Hossan MS1, Fatima A2, Rahmatullah M3, Khoo TJ1, Nissapatorn V4, Galochkina AV5, Slita AV5, Shtro AA6, Nikolaeva Y6, Zarubaev VV7, Wiart C8. Author information 1 School of Pharmacy, University of Nottingham, Malaysia Campus, 43500, Semenyih, Malaysia. 2 Faculty of Pharmacy, Quest International University, 30250, Ipoh, Malaysia. 3 Department of Pharmacy, Faculty of Life Science, University of Development Alternative (UODA), Dhaka, 1207, Bangladesh. 4 School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat, 80161, Thailand. 5 Pasteur Institute of Epidemiology and Microbiology, 14 Mira str, 197101, St. Petersburg, Russia. 6 Influenza Research Institute, 15/17 prof. Popova str, 197376, St. Petersburg, Russia. 7 Pasteur Institute of Epidemiology and Microbiology, 14 Mira str, 197101, St. Petersburg, Russia. zarubaev@gmail.com. 8 School of Pharmacy, University of Nottingham, Malaysia Campus, 43500, Semenyih, Malaysia. Christophe.Wiart@nottingham.edu.my. Abstract Viral respiratory infections are raising serious concern globally. Asian medicinal plants could be useful in improving the current treatment strategies for influenza. The present study examines the activity of five plants from Bangladesh against influenza virus. MDCK cells infected with influenza virus A/Puerto Rico/8/34 (H1N1) were treated with increasing concentrations of ethyl acetate extracts, and their cytotoxicity (CC50), virus-inhibiting activity (IC50), and selectivity index (SI) were calculated. The ethyl acetate extract of fruits of Embelia ribes Burm. f. (Myrsinaceae) had the highest antiviral activity, with an IC50 of 0.2 µg/mL and a SI of 32. Its major constituent, embelin, was further isolated and tested against the same virus. Embelin demonstrated antiviral activity, with an IC50 of 0.3 µM and an SI of 10. Time-of-addition experiments revealed that embelin was most effective when added at early stages of the viral life cycle (0-1 h postinfection). Embelin was further evaluated against a panel of influenza viruses including influenza A and B viruses that were susceptible or resistant to rimantadine and oseltamivir. Among the viruses tested, avian influenza virus A/mallard/Pennsylvania/10218/84 (H5N2) was the most susceptible to embelin (SI = 31), while A/Aichi/2/68 (H3N2) virus was the most resistant (SI = 5). In silico molecular docking showed that the binding site for embelin is located in the receptor-binding domain of the viral hemagglutinin. The results of this study provide evidence that E. ribes can be used for development of a novel alternative anti-influenza plant-based agent. PMID: 29633078 DOI: 10.1007/s00705-018-3842-6