Biomedical R&D Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, Guangdong, People's Republic of China.
Appl Microbiol Biotechnol. 2010 Apr;86(3):805-12. doi: 10.1007/s00253-010-2470-1. Epub 2010 Feb 17.
Human immunodeficiency virus (HIV)/AIDS continues to spread worldwide, and most of the HIV-infected people living in developing countries have little or no access to highly active antiretroviral therapy. The development of efficient and low-cost microbicides to prevent sexual transmission of HIV should be given high priority because there is no vaccine available yet. Cyanovirin-N (CVN) is an entry inhibitor of HIV and many other viruses, and it represents a new generation of microbicide that has specific and potent activity, a different mechanism of action, and unusual chemicophysical stability. In vitro and in vivo antiviral tests suggested that the anti-HIV effect of CVN is stronger than a well-known gp120-targeted antibody (2G12) and another microbicide candidate, PRO2000. CVN is a cyanobacteria-derived protein that has special structural features, making the artificial production of this protein very difficult. In order to develop an efficient and relatively low-cost approach for large-scale production of recombinant CVN to satisfy medical use, this protein has been expressed in many systems by trial and error. Here, to summarize the potential and remaining challenges for the development of this protein into an HIV prevention agent, the progress in the structural mechanism determination, heterologous production and pharmacological evaluation of CVN is reviewed.
人类免疫缺陷病毒(HIV)/艾滋病继续在全球范围内传播,大多数生活在发展中国家的 HIV 感染者几乎无法获得高效抗逆转录病毒治疗。由于目前尚无疫苗,因此应高度重视开发高效且低成本的杀微生物剂来预防 HIV 的性传播。Cyanovirin-N(CVN)是 HIV 和许多其他病毒的进入抑制剂,它代表了新一代的杀微生物剂,具有特定且强效的活性、不同的作用机制和不寻常的理化稳定性。体外和体内抗病毒测试表明,CVN 的抗 HIV 作用比一种著名的 gp120 靶向抗体(2G12)和另一种杀微生物候选物 PRO2000 更强。CVN 是一种来源于蓝藻的蛋白质,具有特殊的结构特征,使得人工生产这种蛋白质非常困难。为了开发一种高效且相对低成本的方法来大规模生产重组 CVN 以满足医疗用途,已经通过反复试验在许多系统中表达了这种蛋白质。在这里,为了总结将这种蛋白质开发成 HIV 预防剂的潜力和剩余挑战,综述了 CVN 的结构机制测定、异源生产和药理学评价方面的进展。