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 μM 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.

• MeSH
• antigeny virové metabolismus   MeSH
• antivirové látky chemická syntéza   farmakologie   MeSH
• buněčné linie MeSH
• glukosidy farmakologie   MeSH
• lignany chemická syntéza   farmakologie   MeSH
• replikace viru účinky léků   MeSH
• vakuolární protonové ATPasy antagonisté a inhibitory   MeSH
• viabilita buněk účinky léků   MeSH
• viry klasifikace   účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The Letter describes the preparation and characterization of a conjugate of isoniazid (INH) with magnetic nanoparticles Fe3O4@SiO2 115±60 nm in size. The INH molecules were attached to the surface of nanoparticles by a covalent pH-sensitive amidine bond. The conjugate was characterized by X-ray diffraction, SEM, dynamic light scattering, IR spectroscopy and microanalysis. The conjugate released isoniazid under in vitro conditions (pH=4; 37 °C; t1/2≈115 s). In addition, the cytotoxicity of the Fe3O4@SiO2-INH conjugate was evaluated in SK-BR-3 cells using the xCELLigence system.

• MeSH
• antibakteriální látky chemická syntéza   chemie   toxicita   MeSH
• difrakce rentgenového záření MeSH
• isoniazid chemická syntéza   chemie   toxicita   MeSH
• koncentrace vodíkových iontů MeSH
• kultivované buňky MeSH
• magnetismus * MeSH
• mikroskopie elektronová rastrovací MeSH
• nanočástice chemie   MeSH
• oxid křemičitý chemie   MeSH
• proliferace buněk účinky léků   MeSH
• železité sloučeniny chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH