Identification of the phytobioactive Polygonum cuspidatum as an antiviral source for restricting dengue virus entry

• Published in: Scientific reports Vol. 10; no. 1; p. 16378
• Main Authors: Kuo, Yu-Ting, Liu, Ching-Hsuan, Li, Jin-Wei, Lin, Chien-Ju, Jassey, Alagie, Wu, Huey-Nan, Perng, Guey Chuen, Yen, Ming-Hong, Lin, Liang-Tzung
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.10.2020; Nature Publishing Group
• Subjects: 631/326/22/1295; 631/326/596/1413; Animal behavior; Animals; Antiviral Agents - pharmacology; Associative learning; Cell Line; Cell Line, Tumor; Chlorocebus aethiops; Dengue - drug therapy; Dengue Virus - drug effects; Extinction behavior; Fallopia japonica - chemistry; Firing pattern; Hepacivirus - drug effects; Humanities and Social Sciences; Humans; multidisciplinary; Phytochemicals - chemistry; Phytochemicals - pharmacology; Plant Extracts - pharmacology; Plants, Medicinal - chemistry; Science; Science (multidisciplinary); Vero Cells; Virus attachment; Virus Attachment - drug effects; Virus Internalization - drug effects; Virus Replication - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-71849-3

Dengue virus (DENV) is a mosquito-borne pathogen that is becoming a serious global threat, owing to its rising incidence in inter-tropical regions that yield over 50 million annual infections. There are currently no approved antiviral agents for the management of dengue, and recent shortcomings in its immunization called for immediate action to develop effective drugs with prophylactic ability to better manage its infection. In an attempt to discover novel antiviral sources, we identified the medicinal herb Polygonum cuspidatum (PC) as a bioactive botanical material against DENV infectivity. Specifically, the methanolic extract from PC rhizomes (PCME) potently inhibited DENV infection without causing significant cytotoxicity. Further examination on the viral life cycle demonstrated that PCME particularly targeted the initial stages of DENV infection, while pre- and post-infection treatments had no effect. More importantly, the PCME could efficiently inactivate DENV free virus particles and block the viral attachment and entry/fusion events without apparently influencing viral replication, egress, and cell-to-cell spread. The antiviral effect of PCME was also recapitulated in infection analysis using DENV pseudoparticles displaying viral structural proteins that mediate DENV particle entry. Besides, PCME treatment also inhibited direct DENV entry into several cell types relevant to its infection and reduced viral infectivity of other members of the Flaviviridae family, including the hepatitis C virus (HCV) and Zika virus (ZIKV). Due to its potency against DENV entry, we suggest that the phytobioactive extract from PC is an excellent starting point as an antiviral source material for further development of therapeutic strategies in the prophylactic management of DENV infection.