Ott S, Wunderli-Allenspach H
Department of Pharmacy, Biopharmacy, Swiss Federal Institute of Technology, Zürich.
Antiviral Res. 1994 May;24(1):37-42. doi: 10.1016/0166-3542(94)90050-7.
The effect of the virostatic norakin on various in vitro activities of influenza viruses was studied. The infectivity of the [A/PR/8/34 (H1N1)] strain for MDCK (Madin Darby canine kidney) cells was reduced by a factor of 10 with 10(-7) M norakin. At 10(-5) M, it was below 1% of the control value without norakin. At higher concentrations (> or = 10(-4) M), cytotoxic effects occurred. Neither hemolysis nor hemagglutination were affected by norakin concentrations up to 10(-4) M. An in vitro fluorescence dequenching assay was used to study the viral fusion activity in the presence and absence of norakin. Fusion between influenza viruses and virus receptor-containing liposomes was not significantly affected up to norakin concentrations of 10(-3) M. However, the intracellular pH in MDCK cells was raised from pH 5.3 (without norakin) to about pH 6 with 10(-5) M norakin. This parallels the pH dependence of PR8 viral activities like hemolysis and fusion. We therefore suggest that norakin does not interact directly with the viral hemagglutinin, but inhibits viral infection through increase of the internal pH in the prelysosomal compartment.
研究了病毒抑制剂诺拉金对流感病毒各种体外活性的影响。对于[A/PR/8/34 (H1N1)]毒株感染MDCK（马-达二氏犬肾）细胞的活性，10(-7) M的诺拉金使其降低了10倍。在10(-5) M时，其低于无诺拉金时对照值的1%。在更高浓度（≥10(-4) M）时，出现细胞毒性作用。高达10(-4) M的诺拉金浓度对溶血和血凝均无影响。采用体外荧光猝灭试验研究有无诺拉金存在时的病毒融合活性。在诺拉金浓度高达10(-3) M时，流感病毒与含病毒受体的脂质体之间的融合未受到显著影响。然而，10(-5) M的诺拉金使MDCK细胞内的pH从pH 5.3（无诺拉金时）升高至约pH 6。这与PR8病毒活性如溶血和融合对pH的依赖性相似。因此，我们认为诺拉金不直接与病毒血凝素相互作用，而是通过提高溶酶体前区室的内部pH来抑制病毒感染。
