Diphyllin Shows a Broad-Spectrum Antiviral Activity against Multiple Medically Important Enveloped RNA and DNA Viruses

0555514 - BC 2023 RIV CH eng J - Journal Article
Štefánik, M. - Bhosale, D. - Haviernik, Jan - Straková, Petra - Fojtiková, M. - Dufková, L. - Huvarová, I. - Salát, J. - Bartáček, J. - Svoboda, J. - Sedlák, M. - Růžek, Daniel - Miller, A. - Eyer, Luděk
Diphyllin Shows a Broad-Spectrum Antiviral Activity against Multiple Medically Important Enveloped RNA and DNA Viruses.
Viruses. Roč. 14, č. 2 (2022), č. článku 354. E-ISSN 1999-4915
R&D Projects: GA MŠMT(CZ) LTAUSA18016
Institutional support: RVO:60077344
Keywords : v-atpase inhibitor * lignans * glycosides * cells * arylnaphthalene * enveloped virus * diphyllin * cleistanthin B * vacuolar ATPase inhibitor * antiviral activity * cytotoxicity
OECD category: Microbiology
Impact factor: 4.7, year: 2022
Method of publishing: Open access
https://www.mdpi.com/1999-4915/14/2/354

Diphyllin is a natural arylnaphtalide lignan extracted from tropical plants of particular importance in traditional Chinese medicine. This compound has been described as a potent inhibitor of vacuolar (H+)ATPases and hence of the endosomal acidification process that is required by numerous enveloped viruses to trigger their respective viral infection cascades after entering host cells by receptor-mediated endocytosis. Accordingly, we report here a revised, updated, and improved synthesis of diphyllin, and demonstrate its antiviral activities against a panel of enveloped viruses from Flaviviridae, Phenuiviridae, Rhabdoviridae, and Herpesviridae families. Diphyllin is not cytotoxic for Vero and BHK-21 cells up to 100 mu M and exerts a sub-micromolar or low-micromolar antiviral activity against tick-borne encephalitis virus, West Nile virus, Zika virus, Rift Valley fever virus, rabies virus, and herpes-simplex virus type 1. Our study shows that diphyllin is a broad-spectrum host cell-targeting antiviral agent that blocks the replication of multiple phylogenetically unrelated enveloped RNA and DNA viruses. In support of this, we also demonstrate that diphyllin is more than just a vacuolar (H+)ATPase inhibitor but may employ other antiviral mechanisms of action to inhibit the replication cycles of those viruses that do not enter host cells by endocytosis followed by low pH-dependent membrane fusion.
Permanent Link: https://hdl.handle.net/11104/0340396