抗补体活性物质临床应用及开发研究进展

Clinical application and development of anti-complement agents:a review

补体系统是先天免疫系统的重要组分之一,类风湿关节炎、自身免疫性溶血性贫血、2019冠状病毒病等多种疾病的发生与补体系统异常密切相关。目前临床常用的补体抑制剂多为化学合成药物,其选择性较差,长期使用容易导致机体免疫能力降低。天然产物来源的抗补体活性成分毒性小、易于被机体消化吸收,其中微生物来源的抗补体活性物质具有独特的优势和应用潜力,可利用基因组挖掘快速发现和鉴定,并利用代谢工程改造和发酵优化大量生产,但目前相关研究仍处于前期研究开发阶段。本综述总结了近年来国内外较常见补体抑制剂的临床应用,同时对微生物来源抗补体活性物质的研发进展进行了讨论,以期为补体抑制剂的临床研究和天然来源新型抗补体活性物质的开发提供参考。

Complement system is a major component of innate immune system,which provides a vital first-line barrier to invading pathogens.The dysfunction of human complement system is related to multiple diseases,such as rheumatoid arthritis,autoimmune hemolytic anemia,and COVID-19.At the moment,most of the clinical complement inhibitors are chemically synthesized,which show poor selectivity and result in decreased immunity after long-term use.In contrast,natural anti-complement agents feature low toxicity and ease of being absorbed.Particularly,anti-complement agents of microbial origin have unique advantages and application potential,which can be discovered and identified by genome mining and produced in large quantities after metabolic engineering and fermentation optimization.However,related research is still in its infancy.Here we summarized the clinical applications of common complement inhibitors in recent years and reviewed the research and development of anti-complement agents of microbial origin,hoping to provide a reference for the clinical research on complement inhibitors and development of natural anti-complement agents.