SARS-CoV-2 Nsp16蛋白分子特征及其对男性生殖功能潜在影响  

Molecular characteristics of SARS-CoV-2 Nsp16 protein and analysis of its potential effect on male reproductive function

作　　者：张凌寒 张婉玉 徐小璐 郭艺红[1] ZHANG Ling-han;ZHANG Wan-yu;XU Xiao-lu;GUO Yi-hong(Center for Reproductive Medicine,the First Affiliated Hospital of Zhengzhou University,Henan Province Key Laboratory of Reproduction and Genetics,Zhengzhou 450001,China)

机构地区：[1]郑州大学第一附属医院生殖医学中心,河南省生殖与遗传重点实验室,郑州450001

出　　处：《中华疾病控制杂志》2021年第4期439-444,共6页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(81571409);河南省高校科技创新团队支持计划(18IRTSTHN030)。

摘　　要：目的COVID-19可能并发生殖功能损伤的问题已引起关注。本研究分析SARS-CoV-2 Nsp16蛋白遗传特征、分子结构与生物功能,探讨病毒侵入睾丸组织后Nsp16对生殖细胞的潜在影响,为该病发病机制和治疗策略研究奠定基础。方法应用生物信息技术和国际生物数据库,分析nsp16基因变异性、Nsp16空间结构与功能及对生殖细胞的潜在影响,并利用DrugBank数据库筛选可靶向结合Nsp16的药物。结果基于3种30株冠状病毒的nsp16序列构建了进化树;SARS-CoV-2毒株间nsp16基因保守性为99%;Nsp16属于亲水蛋白,在体外细胞的半衰期(half-life)是1.9 h;Nsp16具有甲基转移酶活性,具有调节精子和睾丸间质细胞基因和功能蛋白甲基化潜能;Nsp16具有线性B细胞和CTL细胞抗原表位,可能通过激发免疫反应损伤睾丸组织;从DrugBank数据库筛选出2种可靶向结合Nsp16的抑制性药物。结论SARS-CoV-2 Nsp16是基因高度保守的功能蛋白;病毒经血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2)受体侵入睾丸组织后,Nsp16可能通过促进宿主细胞基因和蛋白甲基化机制,影响生殖细胞生长发育。该研究首次报道靶向结合Nsp16的化疗药物,对COVID-19及相关男性生殖系统疾病的防治研究具有重要参考价值。Objective The possibility of coronavirus disease 2019(COVID-19)involving injury to reproductive function has attracted attention.This study analyzed the genetic characteristics,molecular structure and biological function of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Nsp16 protein,and explored potential effects of Nsp16 on germ cells following the virus′invading testicular tissue,aiming to lay basis for studies of pathogenic mechanisms and therapeutic strategies.Methods Bioinformatic techniques and international biological databases were used to analyze nsp16 genetic variability,Nsp16 spatial structure and function,and effects on genes and proteins of germ cells.DrugBank databases were applied in screening for drugs targeted at Nsp16.Results An evolutionary tree was constructed based on the nsp16 sequences of 30 isolates of 3 coronavirus species.The nsp16 conserved property was 99%amongst SARS-CoV-2 isolates.Nsp16 is a hydrophilic protein,with a 1.9 h half-life inside cells in vitro.Nsp16 has methyltransferase activity,showing potential to regulate gene and functional protein methylation of sperm and Leydig cells.Nsp16 has both linear B cell epitopes and CTL cell epitopes,with capacity to induce immune responses and damage to testicular tissue.Two inhibitory drugs targeted at Nsp16 were found by screening the DrugBank database.Conclusions SARS-CoV-2 Nsp16 is a functional protein encoded by a highly conserved gene,may affect germ cell growth and development by promoting methylation of host cellular genes and proteins following the virus′invasion into testis tissue through angiotensin-converting enzyme 2 receptors.This report presents Nsp16-targeted chemotherapeutic drugs for the first time,showing high reference value for prevention and treatment of COVID-19 and related lesions of the male reproductive system.

关 键 词：核糖甲基转移酶 新型冠状病毒 Nsp16 治疗策略 遗传特征 

分 类 号：R373[医药卫生—病原生物学]