title: In vitro antiviral activity of phlorotannins isolated from Ecklonia cava against porcine epidemic diarrhea coronavirus infection and hemagglutination.
abstract: Despite the prepdominat agent causing severe entero-pathogenic diarrhea in swine, there are no effective therapeutical treatment of porcine epidemic diarrhea virus (PEDV). In this study, we evaluated the antiviral activity of five phlorotannins isolated from Ecklonia cava (E. cava) against PEDV. In vitro antiviral activity was tested using two different assay strategies: (1) blockage of the binding of virus to cells (simultaneous-treatment assay) and (2) inhibition of viral replication (post-treatment assay). In simultaneous-treatment assay, compounds 2-5 except compound 1 exhibited antiviral activities of a 50% inhibitory concentration (IC₅₀) with the ranging from 10.8 ± 1.4 to 22.5 ± 2.2 μM against PEDV. Compounds 1-5 were completely blocked binding of viral spike protein to sialic acids at less than 36.6 μM concentrations by hemagglutination inhibition. Moreover, compounds 4 and 5 of five phlorotannins inhibited viral replication with IC₅₀ values of 12.2 ± 2.8 and 14.6 ± 1.3 μM in the post-treatment assay, respectively. During virus replication steps, compounds 4 and 5 exhibited stronger inhibition of viral RNA and viral protein synthesis in late stages (18 and 24 h) than in early stages (6 and 12 h). Interestingly, compounds 4 and 5 inhibited both viral entry by hemagglutination inhibition and viral replication by inhibition of viral RNA and viral protein synthesis, but not viral protease. These results suggest that compounds isolated from E. cava have strong antiviral activity against PEDV, inhibiting viral entry and/or viral replication, and may be developed into natural therapeutic drugs against coronavirus infection.
authors.affiliation: Infection Control Material Research Center, AI Control Material Research Center and Bioindustrial Process Reasearch Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si, Jeonbuk 580-185, Republic of Korea.
authors.forename: Hyung-Jun
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Ryu
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Kim
authors.forename: Naaleum
authors.initials: N
authors.lastname: Song
authors.forename: Cha Young
authors.initials: CY
authors.lastname: Kim
authors.forename: Mun-Chual
authors.initials: MC
authors.lastname: Rho
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Jeong
authors.forename: Kyoung-Oh
authors.initials: KO
authors.lastname: Cho
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology; D018352:Coronavirus Infections / Q000097:blood / Q000188:drug therapy / Q000662:veterinary* / Q000821:virology; D006384:Hemagglutination / Q000187:drug effects; D006386:Hemagglutination Tests; D000459:Phaeophyceae / Q000737:chemistry*; D053485:Porcine epidemic diarrhea virus / Q000187:drug effects*; D013552:Swine; D013553:Swine Diseases / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D013634:Tannins / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D013634:Tannins