Vere Hodge R Anthony
Vere Hodge Antivirals Ltd, Old Denshott, Leigh, Reigate, Surrey, UK.
Antiviral Res. 2014 Nov;111:143-53. doi: 10.1016/j.antiviral.2014.08.009. Epub 2014 Sep 16.
The 27th International Conference on Antiviral Research (ICAR) was held in Raleigh, North Carolina, USA from May 12 to 16, 2014. This article summarizes the principal invited lectures. John Drach (Elion Award) described the early days of antiviral drugs and their novel modes of action. Piet Herdewijn (Holý Award) used evolutionary pressure to select DNA polymerases that accept nucleoside analogs. Replacing thymine by 5-chlorouracil led to the generation of a new form of Escherichia coli. Adrian Ray (Prusoff Award) demonstrated how prodrugs can markedly improve both the efficacy and safety of potential drugs. The keynote addresses, by David Margolis and Myron Cohen, tackled two emerging areas of HIV research, to find an HIV "cure" and to prevent HIV transmission, respectively. These topics were discussed further in other presentations - a cure seems to be a distant prospect but there are exciting developments for reducing HIV transmission. TDF-containing vaginal rings and GSK-744, as a long-lasting injection, offer great hope. There were three mini-symposia. Although therapy with TDF/FTC gives excellent control of HBV replication, there are only a few patients who achieve a functional cure. Myrcludex, an entry inhibitor, is active against both HBV and HDV. The recent progress with HBV replication in cell cultures has transformed the search for new antiviral compounds. The HBV capsid protein has been recognized as key player in HBV DNA synthesis. Unexpectedly, compounds which enhance capsid formation, markedly reduce HBV DNA synthesis. The development of BCX4430, which is active against Marburg and Ebola viruses, is of great current interest.
第27届国际抗病毒研究会议（ICAR）于2014年5月12日至16日在美国北卡罗来纳州罗利市举行。本文总结了主要的特邀讲座内容。约翰·德拉奇（获得埃利恩奖）讲述了抗病毒药物的早期情况及其新颖的作用方式。皮特·赫德维恩（获得霍利奖）利用进化压力筛选出能接受核苷类似物的DNA聚合酶。用5-氯尿嘧啶取代胸腺嘧啶导致了一种新型大肠杆菌的产生。阿德里安·雷（获得普鲁索夫奖）展示了前药如何能显著提高潜在药物的疗效和安全性。大卫·马戈利斯和迈伦·科恩的主题演讲分别探讨了艾滋病病毒研究中两个新兴领域，即寻找艾滋病病毒“治愈方法”和预防艾滋病病毒传播。这些主题在其他报告中得到了进一步讨论——治愈似乎是一个遥远的前景，但在减少艾滋病病毒传播方面有令人兴奋的进展。含替诺福韦的阴道环和作为长效注射剂的GSK-744带来了很大希望。会议设有三场小型专题讨论会。虽然用替诺福韦/恩曲他滨治疗能很好地控制乙肝病毒复制，但只有少数患者能实现功能性治愈。进入抑制剂Myrcludex对乙肝病毒和丁型肝炎病毒均有活性。细胞培养中乙肝病毒复制的最新进展改变了新型抗病毒化合物的研发方向。乙肝病毒衣壳蛋白已被认为是乙肝病毒DNA合成中的关键因素。出乎意料的是，增强衣壳形成的化合物能显著降低乙肝病毒DNA合成。对马尔堡病毒和埃博拉病毒有活性的BCX4430的研发目前备受关注。
