Davidson Andrew, Siddell Stuart
Department of Pathology and Microbiology, Medical and Veterinary Sciences, University of Bristol, Bristol, UK.
Curr Opin Infect Dis. 2003 Dec;16(6):565-71. doi: 10.1097/00001432-200312000-00009.
Severe acute respiratory syndrome is a new, sometimes lethal disease of humans that is caused by a novel coronavirus. To date there have been over 750 related deaths and there is clearly an urgent need to develop specific antiviral drugs to combat this disease. In this review, the authors shall focus on the molecular biology of the coronavirus and suggest how this information can be used to identify possible targets for antiviral drugs.
Within a remarkably short period of time, the severe acute respiratory syndrome coronavirus has been isolated, its genome has been sequenced and the structure of at least one key viral enzyme has been deduced. In addition, bioinformatic analysis has predicted a number of enzymatic activities associated with proteins of the viral replicase-transcriptase complex. In some cases, these functions have been confirmed by biochemical analysis. Thus, there has been significant progress in the rational approach to anti-severe acute respiratory syndrome coronavirus drug design. This approach, combined with the random screening of licensed compounds or existing compound libraries, should result in the identification of novel lead compounds and the expeditious development of antiviral drugs.
Although the initial severe acute respiratory syndrome epidemic has been controlled by conventional measures, the animal reservoir for the coronavirus progenitor has not been identified. It is therefore likely that the virus will be reintroduced into the human population in the future. When this happens, the most economical and effective way to contain the virus will be the therapeutic use of antiviral drugs.
严重急性呼吸综合征是一种由新型冠状病毒引起的、有时会致命的新型人类疾病。迄今为止,已有超过750人死于该病,显然迫切需要研发特效抗病毒药物来对抗这种疾病。在这篇综述中,作者将聚焦于冠状病毒的分子生物学,并探讨如何利用这些信息来确定抗病毒药物的潜在靶点。
在极短的时间内,严重急性呼吸综合征冠状病毒已被分离出来,其基因组已被测序,至少一种关键病毒酶的结构已被推导出来。此外,生物信息学分析预测了一些与病毒复制酶-转录酶复合体蛋白相关的酶活性。在某些情况下,这些功能已通过生化分析得到证实。因此,在合理设计抗严重急性呼吸综合征冠状病毒药物方面取得了重大进展。这种方法与对已获许可的化合物或现有化合物库进行随机筛选相结合,应能鉴定出新的先导化合物,并加速抗病毒药物的研发。
尽管最初的严重急性呼吸综合征疫情已通过常规措施得到控制,但冠状病毒祖病毒的动物宿主尚未确定。因此,该病毒未来有可能再次传播给人类。一旦发生这种情况,控制病毒传播最经济有效的方法将是使用抗病毒药物进行治疗。