BACKGROUND: HHV-6 replication requires complex and poorly understood interactions between viral and cellular factors. OBJECTIVES: Several natural compounds or broad-acting pharmacological agents were studied in an attempt to discover new targets for anti-HHV-6 therapy. STUDY DESIGN: The antiviral activity was determined in human T-lymphoblasts, using HHV-6A (GS)-infected HSB-2 cells, HHV-6B (Z29)-infected MOLT-3 cells and HHV- 6B (HST)-infected MT4 cells. Virus replication was measured by CPE and qPCR assay. Foscarnet was included as the reference compound. RESULTS: Among the 15 natural compounds tested, only 'red marine algae' (an extract rich in sulfated polysaccharides) exhibited strong activity when added during virus adsorption. Among the broad-acting pharmacological agents, chloroquine, artemisinin, hypericin, ribavirin, resveratrol and glycyrrhizic acid were all inactive. Amantadine produced a reproducible inhibition of HHV-6 replication, albeit at relatively high concentrations. Except for lamotrigine, which was moderately active against HHV-6B, several antiepileptic drugs were shown to have no activity. We included several compounds which we previously described as potent HHV-6 inhibitors, i.e., the non-nucleoside inhibitor CMV423 and the acyclic nucleoside phosphonate analogues cidofovir and 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-3-deazaadenine. The latter compound exhibited remarkable anti-HHV-6 activity. CONCLUSION: Further optimization of compounds belonging to diverse classes of antiherpetic agents, for their specific action against HHV-6, is warranted.
BACKGROUND:HHV-6 replication requires complex and poorly understood interactions between viral and cellular factors. OBJECTIVES: Several natural compounds or broad-acting pharmacological agents were studied in an attempt to discover new targets for anti-HHV-6 therapy. STUDY DESIGN: The antiviral activity was determined in human T-lymphoblasts, using HHV-6A (GS)-infected HSB-2 cells, HHV-6B (Z29)-infected MOLT-3 cells and HHV- 6B (HST)-infected MT4 cells. Virus replication was measured by CPE and qPCR assay. Foscarnet was included as the reference compound. RESULTS: Among the 15 natural compounds tested, only 'red marine algae' (an extract rich in sulfated polysaccharides) exhibited strong activity when added during virus adsorption. Among the broad-acting pharmacological agents, chloroquine, artemisinin, hypericin, ribavirin, resveratrol and glycyrrhizic acid were all inactive. Amantadine produced a reproducible inhibition of HHV-6 replication, albeit at relatively high concentrations. Except for lamotrigine, which was moderately active against HHV-6B, several antiepileptic drugs were shown to have no activity. We included several compounds which we previously described as potent HHV-6 inhibitors, i.e., the non-nucleoside inhibitor CMV423 and the acyclic nucleoside phosphonate analogues cidofovir and 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-3-deazaadenine. The latter compound exhibited remarkable anti-HHV-6 activity. CONCLUSION: Further optimization of compounds belonging to diverse classes of antiherpetic agents, for their specific action against HHV-6, is warranted.
Authors: Randy Chi Fai Cheung; Jack Ho Wong; Wen Liang Pan; Yau Sang Chan; Cui Ming Yin; Xiu Li Dan; He Xiang Wang; Evandro Fei Fang; Sze Kwan Lam; Patrick Hung Kui Ngai; Li Xin Xia; Fang Liu; Xiu Yun Ye; Guo Qing Zhang; Qing Hong Liu; Ou Sha; Peng Lin; Chan Ki; Adnan A Bekhit; Alaa El-Din Bekhit; David Chi Cheong Wan; Xiu Juan Ye; Jiang Xia; Tzi Bun Ng Journal: Appl Microbiol Biotechnol Date: 2014-02-23 Impact factor: 4.813
Authors: Mark N Prichard; Samuel L Frederick; Shannon Daily; Katherine Z Borysko; Leroy B Townsend; John C Drach; Earl R Kern Journal: Antimicrob Agents Chemother Date: 2011-02-07 Impact factor: 5.191
Authors: Diane F Birt; Mark P Widrlechner; Kimberly Dp Hammer; Matthew L Hillwig; Jingqiang Wei; George A Kraus; Patricia A Murphy; Joeann McCoy; Eve S Wurtele; Jeffrey D Neighbors; David F Wiemer; Wendy J Maury; Jason P Price Journal: Pharm Biol Date: 2009 Impact factor: 3.503