CN114469919B - Dha或其衍生物在制备冠状病毒抑制剂中的应用 - Google Patents
Dha或其衍生物在制备冠状病毒抑制剂中的应用 Download PDFInfo
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Abstract
本发明公开了DHA或其衍生物在制备冠状病毒抑制剂中的应用,属于医用配制品领域。本发明还公开了一种冠状病毒抑制剂,所述冠状病毒抑制剂包括DHA或其衍生物和抗冠状病毒的抗体,所述冠状病毒可为β属冠状病毒,如SARS‑CoV‑2。本发明提供的试验结果表明DHA可影响RBD热变温度,降低RBD蛋白的稳定性;同时,DHA或其衍生物与抗新冠抗体联用可提高抗体的中和率。
Description
技术领域
本发明属于医用配制品领域,具体涉及DHA或其衍生物在制备冠状病毒抑制剂中的应用。
背景技术
新型冠状病毒,是一种可引起人新型冠状病毒肺炎 (COVID-19) 的新发呼吸道病原体,与重症急性呼吸道综合征冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)同属于β-冠状病毒,具有较高的传染性和一定的致死率。新型冠状病毒,世界卫生组织称其为2019-nCoV,世界病毒分类委员会称其为SARS-CoV-2。
SARS-CoV-2是一种单链RNA 病毒,该病毒进入宿主细胞的关键蛋白是位于病毒颗粒表面的刺突糖蛋白。刺突糖蛋白全长1274个氨基酸,其中319-529位的氨基酸折叠形成的结构域介导与宿主细胞膜受体结合,因而这些氨基酸所组成的结构域也称之为RBD结构域(Receptor binding domain,RBD)。RBD结构域是新冠病毒药物研发的重要靶标。
抗体(antibody,Ab)是B细胞被B细胞抗原表位特异性刺激后增殖分化为浆细胞所产生的效应免疫分子,介导体液免疫。当抗体与病原体表面,或者细菌毒素关键表位相结合,则封闭了病原体或毒素的毒力结构,使病毒丧失感染能力,并使毒素丧失毒力,称为中和作用(neutralization)。大部分抗体是通过向T-淋巴细胞发出锁定抗原的信号,激发细胞免疫反应,杀死病毒,而中和抗体是B淋巴细胞产生的能够与病原微生物表面的抗原结合的一类抗体,是特异针对病毒中和表位产生的抗体,可直接靶定到病毒中和表位,使病毒失去结合受体的能力。
靶向病毒的疫苗和药物研发面对的另外一个巨大挑战是病毒的高度变异性,尤其是冠状病毒这类单链RNA病毒。针对易产生变异和耐药性的病毒,目前比较成功的治疗策略是“鸡尾酒疗法”,即通过把不同靶向的药物分子进行配比后复方联合使用,可以从病毒感染周期的不同阶段对其进行多重遏制,有效抑制病毒变异逃逸,进而实现病毒控制与清除。这一策略已经成功用于HIV病毒以及丙肝病毒的临床治疗。目前我国首个获批国产中和抗体联合治疗药物也已经写入新版新冠肺炎诊疗方案中。
发明内容
本发明要解决的技术问题是如何抑制冠状病毒的活性,例如抑制SARS-CoV-2的侵入活性。
为解决上述技术问题,第一个方面,本发明提供DHA或其衍生物的应用,所述应用可为以下(a)和/或(b)和/或(c):
(a)DHA或其衍生物在制备增强抗冠状病毒的抗体对冠状病毒的抗病毒活性的产品(药物或疫苗)中的应用;
(b)DHA或其衍生物在制备预防和/或治疗冠状病毒所致疾病或冠状病毒感染的药物中的应用;
(c)DHA或其衍生物在制备冠状病毒抑制剂中的应用。
进一步地,上述的应用中,所述冠状病毒可为β冠状病毒属病毒,α冠状病毒属病毒,γ冠状病毒属病毒和/或δ冠状病毒属病毒。
进一步地,上述的应用中,所述β冠状病毒属病毒可为SARS-CoV-2。
本发明中,DHA即二十二碳六烯酸,英文名为Docosahexaenoic Acid,简称DHA。
进一步地,上述的应用中,所述衍生物可为DHA环氧化物 (DHA-epoxides, EDPs)。
本发明中,DHA环氧化物的制备方法如下:
将50 mg DHA溶解在2 mL的二氯甲烷中,得到2 mL DHA浓度为25 mg/mL的DHA二氯甲烷溶液。将该2 mL DHA二氯甲烷溶液与49.5 mg的间氯过氧苯甲酸(mCPBA)室温(25℃)反应(进行非特异性环氧化反应)1 小时后,加入等体积10% NaHCO3水溶液淬灭mCPBA,水层用等体积的二氯甲烷重新萃取三次,将水层从有机层中取出,用等体积的二氯甲烷重新萃取水层,合并有机层,真空干燥。使用Waters CSH C18反相色谱柱 (1.7 μm, 2.1 mm × 100mm,),采用流动相梯度洗脱,收集保留时间为15.62 min的洗脱峰即为DHA环氧化物EDPs。
液相色谱条件如下:
色谱柱:Waters CSH C18反相色谱柱,粒径1.7 μm,2.1 mm ×100 mm;
柱温:30℃;
流速:0.25 mL/min;
进样量:2 μL;
流动相及梯度洗脱程序如说明书附图中图4所示。
进一步地,本发明中所述抗病毒活性也可称为抑制病毒活性,具体可为抑制病毒进行细胞融合和/或抑制病毒侵入细胞和/或抑制病毒复制。
所述抗冠状病毒的抗体可为冠状病毒的中和抗体,如P2C-1F11或P2B-1G5。
其中,P2C-1F11的重链可变区(VH)的氨基酸序列是SEQ ID No.1,核苷酸序列是SEQ ID No.5;轻链可变区(VL)的氨基酸序列为SEQ ID No.2,核苷酸序列是SEQ ID No.6;
P2B-1G5的重链可变区(VH)的氨基酸序列是SEQ ID No.3,核苷酸序列是SEQ IDNo.7;轻链可变区(VL)的氨基酸序列为SEQ ID No.4,核苷酸序列是SEQ ID No.8。
中和抗体P2C-1F11和P2B-1G5的重链恒定区均为人IgG1,其氨基酸序列为SEQ IDNo.9,核苷酸序列为SEQ ID No.12;中和抗体P2B-1G5的轻链恒定区为lambda,其氨基酸序列为SEQ ID No.10,核苷酸序列为SEQ ID No.13;中和抗体P2C-1F11的轻链恒定区为Kappa,其氨基酸序列为SEQ ID No.11,核苷酸序列为SEQ ID No.14。
为解决上述技术问题,第二个方面,本发明提供冠状病毒抑制剂,所述冠状病毒抑制剂包括M1和M2,所述M1可为DHA或其衍生物,所述M2可为抗冠状病毒的抗体。
所述冠状病毒抑制剂对冠状病毒具有抗病毒活性。
进一步地,上述的冠状病毒抑制剂中,所述抗冠状病毒的抗体与DHA或其衍生物的质量比可为0.075:1-2.43:1。
进一步地,上述的冠状病毒抑制剂中,所述冠状病毒可为β冠状病毒属病毒,α冠状病毒属病毒,γ冠状病毒属病毒和/或δ冠状病毒属病毒。
进一步地,上述的冠状病毒抑制剂中,所述β冠状病毒属病毒可为SARS-CoV-2。
进一步地,上述的冠状病毒抑制剂中,所述衍生物可为所述DHA环氧化物(DHA-epoxides, EDPs)。
进一步地,上述的冠状病毒抑制剂中,所述抗冠状病毒的抗体可为冠状病毒的中和抗体,如所述P2C-1F11或所述P2B-1G5。
本发明所述冠状病毒抑制剂或药物中,DHA或其衍生物可作为有效成分之一。
本发明中,制备冠状病毒抑制剂或药物时,还可加入载体材料。
所述载体材料包括但不限于水溶性载体材料(如聚乙二醇、聚乙烯吡咯烷酮、有机酸等)、难溶性载体材料(如乙基纤维素、胆固醇硬脂酸酯等)、肠溶性载体材料(如醋 酸纤维素酞酸酯和羧甲乙纤维素等)。使用这些材料可以制成多种剂型,包括但不限于片剂、胶囊、滴丸、气雾剂、丸剂、粉剂、溶液剂、混悬剂、乳剂、颗粒剂、脂质体、透皮剂、口含片、栓剂、冻干粉针剂等。可以是普通制剂、缓释制剂、控释制剂及各种微粒给药系统。为了将单位给药剂型制成片剂,可以广泛使用本领域公知的各种载体。关于载体的例子是,例如稀释剂与吸收剂,如淀粉、糊精、硫酸钙、乳糖、甘露醇、蔗糖、氯化钠、葡萄糖、尿素、碳酸钙、白陶土、微晶纤维素、硅酸铝等;湿润剂与粘合剂,如水、甘油、聚乙二醇、乙醇、丙醇、淀粉浆、糊精、糖浆、蜂蜜、葡萄糖溶液、阿拉伯胶浆、明胶浆、羧甲基纤维素钠、紫胶、甲基纤维素、磷酸钾、聚乙烯吡咯烷酮等;崩解剂,例如干燥淀粉、海藻酸盐、琼脂粉、褐藻淀粉、碳酸氢钠与枸橼酸、碳酸钙、聚氧乙烯、山梨糖醇脂肪酸酯、十二烷基磺酸钠、甲基纤维素、乙基纤维素等;崩解抑制剂,例如蔗糖、三硬脂酸甘油酯、可可脂、氢化油等;吸收促进剂,例如季铵盐、十二烷基硫酸钠等;润滑剂,例如滑石粉、二氧化硅、玉米淀粉、硬脂酸盐、硼酸、液体石蜡、聚乙二醇等。还可以将片剂进一步制成包衣片,例如糖包衣片、薄膜包衣片、肠溶包衣片,或双层片和多层片。为了将单位给药剂型制成丸剂,可以广泛使用本领域公知的各种载体。关于载体的例子是,例如稀释剂与吸收剂,如葡萄糖、乳糖、淀粉、可可脂、氢化植物油、聚乙烯吡咯烷酮、高岭土、滑石粉等;粘合剂如阿拉伯胶、黄蓍胶、明胶、乙醇、蜂蜜、液糖、米糊或面糊等;崩解剂,如琼脂粉、干燥淀粉、海藻酸盐、十二烷基磺酸钠、甲基纤维素、乙基纤维素等。为了将单位给药剂型制成栓剂,可以广泛使用本领域公知的各种载体。关于载体的例子是,例如聚乙二醇、卵磷脂、可可脂、高级醇、高级醇的酯、明胶、半合成甘油酯等。为了将单位给药剂型制成注射用制剂,如溶液剂、乳剂、冻干粉针剂和混悬剂,可以使用本领域常用的所有稀释剂,例如,水、乙醇、聚乙二醇、1,3-丙二醇、乙氧基化的异硬脂醇、多氧化的异硬脂醇、聚氧乙烯山梨醇脂肪酸酯等。另外,为了制备等渗注射液,可以向注射用制剂中添加适量的氯化钠、葡萄糖或甘油,此外,还可以添加常规的助溶剂、缓冲剂、pH调节剂等。此外,如需要,也可以向药物制剂中添加着色剂、防腐剂、香料、矫味剂、甜味剂或其它材料。
使用上述剂型可以经注射给药,包括皮下注射、静脉注射、肌肉注射和腔内注射等;呼吸道给药,如经鼻腔;粘膜给药。
本发明基于发明人创建的药物筛选平台,以新冠刺突糖蛋白RBD结构域蛋白为靶点进行药物筛选,发现了不饱和脂肪酸DHA能够结合新冠病毒RBD结构域蛋白。药效研究结果进一步表明,DHA及其环氧衍生物具有协同病毒中和抗体发挥抗病毒感染的功能和效果,可用于制备预防和/或治疗冠状病毒所致疾病或冠状病毒感染的药物。
附图说明
图1新冠刺突糖蛋白RBD结构域蛋白的SDS-PAGE凝胶电泳结果。
图2为表面等离子共振实验显示DHA结合新冠刺突糖蛋白RBD结构域。
图3为热漂移实验显示生理条件下,DHA影响新冠病毒刺突糖蛋白RBD结构域稳定性。
图4为DHA环氧化物制备中液相色谱的流动相及梯度洗脱程序。
图5为新冠假病毒入侵实验显示DHA及其衍生物(EDPs)可以协同增强中和抗体P2C-1F11抑制病毒入侵。
图6为新冠假病毒入侵实验显示DHA及其衍生物(EDPs)可以协同增强中和抗体P2B-1G5抑制病毒入侵。
图7为抗体与DHA或其衍生物添加浓度、添加量及质量比值。
图8为中和抗体IC50测定数据。
具体实施方式
下面结合具体实施方式对本发明进行进一步的详细描述,给出的实施例仅为了阐明本发明,而不是为了限制本发明的范围。以下提供的实施例可作为本技术领域普通技术人员进行进一步改进的指南,并不以任何方式构成对本发明的限制。
下述实施例中的实验方法,如无特殊说明,均为常规方法,按照本领域内的文献所描述的技术或条件或者按照产品说明书进行。下述实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
重组RBD蛋白表达载体pFastBac-Dual质粒、Sf9细胞以及Hi5细胞由清华大学生命科学学院王新泉课题组惠赠,在文献“Lan, J., et al., Structure of the SARS-CoV-2spike receptor-binding domain bound to the ACE2 receptor. Nature, 2020. 581(7807): p. 215-220.”中公开,公众可从申请人获得上述生物材料,所得上述生物材料只为重复本发明的实验所用,不可作为其它用途使用。
假病毒rVSV-eGFP-SARS-CoV-2由中国科学院动物研究所郑爱华课题组赠予,在文献“Li, H., et al., Establishment of replication-competent vesicularstomatitis virus-based recombinant viruses suitable for SARS-CoV-2 entry andneutralization assays. Emerg Microbes Infect, 2020. 9(1): p. 2269-2277. ”中公开,公众可从申请人获得上述生物材料,所得上述生物材料只为重复本发明的实验所用,不可作为其它用途使用。
DHA购买于上海毕得医药科技股份有限公司,货号为BD121651,CAS No. 6217-54-5。
实施例1、重组RBD蛋白制备
1.1、重组RBD蛋白表达载体构建
新冠刺突糖蛋白受体结合区域(Receptor binding domain,RBD,下文中简称为RBD)蛋白的编码序列(核苷酸序列是SEQ ID No.2)通过同源重组的方法构建于pFastBac-Dual表达载体质粒中,获得的阳性重组表达载体命名为pFastBac-RBD。重组表达载体pFastBac-RBD的结构为:用核苷酸序列是SEQ ID No.2的DNA分子替换骨架载体pFastBac-Dual的多克隆位点BamHI-HindIII之间的序列,保持pFastBac其他核苷酸序列不变得到的重组表达载体。
RBD的氨基酸序列如SEQ ID No.1,其中SEQ ID No.1第1-20位是信号肽,第21-214位是RBD蛋白的氨基酸序列,第215-220是His标签。
将50 ng pFastBac-RBD质粒转化DH10β感受态细胞(康体生命,KTSM102L),通过抗性和蓝白斑筛选到重组克隆,扩增培养5 mL菌液,提取bacmid 后使用 FuGENE ® HD 转染试剂( Promega, E2311 )转染Sf9昆虫细胞,培养48 hr 收集细胞上清液,该上清液包含重组病毒P1。获得的P1病毒再次侵染新鲜培育的Sf9昆虫细胞,培养72 hr后收集细胞上清液,该上清液包含病毒滴度较高的P2病毒,病毒液4℃保存。具体操作流程按照官方使用说明书(Bac-to-Bac™ Baculovirus Expression System USER GUIDE,Publication NumberMAN0000414)。
1.2、重组RBD蛋白表达纯化
我们选用Hi5昆虫细胞分泌表达RBD。将Sf9细胞包装好的P2病毒按1:200的体积比加入到细胞密度为1.2~1.5×106/mL的Hi5细胞中,48 hr后收取病毒上清,利用2 mL Ni亲和重力柱(常州天地人和生物科技有限公司,SA00501L)捕获目的蛋白RBD,经20个柱体积的洗杂缓冲盐冲洗后,5个柱体积(10 mL)洗脱缓冲盐洗脱获得RBD蛋白,通过SDS-PAGE聚丙烯酰胺凝胶蛋白电泳(SDS-PAGE)检测蛋白纯度,电泳结果如图1所示:箭头所指的条带大小接近25kDa的为目的蛋白RBD(理论大小为23 kDa)。
洗杂缓冲盐成分:PBS pH7.4,添加pH 7.5的4M 咪唑储液,至咪唑终浓度为 20mM;
洗脱缓冲盐成分:PBS pH7.4,添加pH 7.5的4M 咪唑储液,至咪唑终浓度为200mM。
实施例2、高通量筛选发现DHA结合RBD及两者相互作用的验证
2.1、表面等离子共振成像实验筛选发现DHA结合RBD
我们通过SPRi表面等离子共振成像技术手段发现DHA可以结合RBD。具体的实验方法如下:
利用Plexera HT SPRi生物分子相互作用分析仪高通量检测蛋白-小分子的亲和力。首先利用Arrayjet飞行喷墨式生物芯片点样平台将化合物库中的小分子DMSO溶液以微阵列的形式打印在Plexera提供的小分子光交联芯片表面,芯片在真空中经过干燥后,通过紫外激发交联反应,将小分子共价固定在芯片表面,清洗多余的小分子的芯片上机进行检测。将RBD蛋白进行梯度稀释(0.1、1、2、10 μM/L),浓度从低到高以5 μL/sec的速度依次通入芯片进行亲和力检测,总共流通时间为120 sec,每个样品检测的间隔,使用10mM pH 2.0甘氨酸盐酸溶液清洗3min进行重生。采集得到的高通量数据使用Langmuir 1:1模型进行动力学拟合。
结果如图2所示,图2中,纵坐标为响应值,横坐标为流通时间;4个不同灰度值颜色的曲线代表流通不同浓度0.1、1、2、10 μM/L的RBD蛋白所获得的信号,曲线颜色越深,浓度越高。结果表明DHA对流通的RBD蛋白有明显的响应信号,且随着RBD蛋白浓度的升高,响应值增大,表现出了明显的浓度剂量效应,这显示在体外DHA能够结合RBD。
2.2、DHA结合RBD的生化互作验证
TSA实验(Thermal Shift Assay,热漂移检测)结果显示,在生理pH和盐离子浓度条件下,与等体积DMSO(二甲集亚砜) 溶剂空白对照组相比,DHA促使RBD热变温度降低,降低了 RBD蛋白的稳定性。
具体实验步骤如下:
RBD蛋白经截留孔径为10 kDa浓缩管浓缩至4mg/mL (0.16 mM/L)。通过TSA(Thermal Shift Assay,热漂移分析)实验方法检测DHA与RBD蛋白的分子互作,实验采用等体积DMSO作为溶剂空白对照。反应体系如下:在体系中加入0.16 mM/L的RBD蛋白1μL与1. 6mM/L的DHA小分子1μL (用DMSO溶解, RBD与DHA摩尔比为1:10) ,加入50 x工作液的SYPROOrange蛋白染料(Thermo Fisher,S6651) 2 μL,用PBS补充至反应终体积为20 μL。
利用荧光定量PCR仪运行下述程序并采集荧光数据:25℃孵育5min;25-95℃,0.5℃/10 sec程序梯度升温,同步采集荧光信号。
实验结果如图3所示,纵坐标为荧光信号的变化率(荧光信号对温度的一阶负导数),横坐标为温度,在生理pH和盐离子浓度条件下,与作为溶剂空白对照的DMSO对照组(灰色点图)相比,添加DHA组(黑色点图),蛋白融解曲线左移,融解温度从49℃降低为38℃,表明DHA促进RBD蛋白疏水核心的暴露,降低了RBD的稳定性。
实施例3、DHA协同增强抗体抑制新冠假病毒入侵
本发明基于清华大学医学院张林琦课题组构建的新冠假病毒入侵体系对DHA的抗病毒活性进行了检测,该体系相关的病毒制备、抗体药物活性检测方法以及数据处理方法均已在文献中公开。
结果表明:DHA及其衍生物EDPs可以有效增强多个新冠病毒中和抗体中和病毒的效应。
以编号为P2C-1F11和P2B-1G5的中和抗体为例,在添加DHA或者DHA衍生物EDPs的情况下,量效关系曲线明显左移。就IC50来说,P2C-1F11的IC50由0.039 μg/mL 分别降低为0.023 μg/mL(DHA)和0.013μg/mL(EDPs),P2B-1G5的IC50由0.047 μg/mL分别降低到0.018μg/mL(DHA)和0.012 μg/mL(EDPs),这说明无论是DHA还是其环氧化物EDPs都能增强中和抗体的病毒中和率,提高抗体中和新冠病毒的能力。
DHA及其衍生物(EDPs)增强中和抗体P2C-1F11中和率的结果如图5所示。
DHA及其衍生物(EDPs)增强中和抗体P2B-1G5中和率的结果如图6所示。
结果表明:与添加溶剂DMSO的空白对照组相比,DHA及其衍生物(EDPs)能够有效地协同增强中和抗体抑制新冠病毒假病毒入侵细胞的能力,具有抗新冠病毒的功效。
3.1、DHA环氧化物(EDPs)的制备
DHA环氧化物EDPs的制备方法如下:
将50 mg DHA溶解在2 mL的二氯甲烷中,得到2 mL DHA浓度为25 mg/mL的DHA二氯甲烷溶液。将该2 mL DHA二氯甲烷溶液与49.5 mg的间氯过氧苯甲酸(mCPBA)室温(25℃)反应(进行非特异性环氧化反应)1 小时后,加入等体积10% NaHCO3水溶液淬灭mCPBA,水层用等体积的二氯甲烷重新萃取三次,将水层从有机层中取出,用等体积的二氯甲烷重新萃取水层,合并有机层,真空干燥。使用Waters CSH C18反相色谱柱 (1.7 μm, 2.1mm × 100mm,),采用流动相梯度洗脱,收集保留时间为15.62min的洗脱峰即为DHA环氧化物EDPs。
液相色谱条件如下:
色谱柱:Waters CSH C18反相色谱柱,粒径1.7 μm,2.1 mm ×100 mm;
柱温:30℃;
流速:0.25 mL/min;
进样量:2 μL;
流动相及梯度洗脱结果见图4:
3.2、SARS-CoV-2假病毒的制备
本实验使用的SARS-CoV-2假病毒为下述文献中的rVSV-eGFP-SARS-CoV-2,该假病毒基于水疱性口角炎病毒(vesicular stomatitis virus, VSV)制备,由中国科学院动物研究所郑爱华课题组赠予,该假病毒材料及制备方法在文献“Li, H., et al.,Establishment of replication-competent vesicular stomatitis virus-basedrecombinant viruses suitable for SARS-CoV-2 entry and neutralization assays.Emerg Microbes Infect, 2020. 9(1): p. 2269-2277.”中公开。
3.3、DHA协同增强抗体中和率的测定实验
本实验采用新冠病毒中和抗体P2C-1F11和P2B-1G5,中和抗体P2C-1F11和P2B-1G5的制备方法参照公开日为2021年09月23日、公开号为WO2021185346A1的专利文献中实施例1中所示的方法。
其中,P2C-1F11的重链可变区(VH)的氨基酸序列是SEQ ID No.1,核苷酸序列是SEQ ID No.5;轻链可变区(VL)的氨基酸序列为SEQ ID No.2,核苷酸序列是SEQ ID No.6;
P2B-1G5的重链可变区(VH)的氨基酸序列是SEQ ID No.3,核苷酸序列是SEQ IDNo.7;轻链可变区(VL)的氨基酸序列为SEQ ID No.5,核苷酸序列是SEQ ID No.8。
中和抗体P2C-1F11和P2B-1G5的重链恒定区均为人IgG1,其氨基酸序列为SEQ IDNo.9,核苷酸序列为SEQ ID No.12;中和抗体P2B-1G5的轻链恒定区为lambda,其氨基酸序列为SEQ ID No.10,核苷酸序列为SEQ ID No.13;中和抗体P2C-1F11的轻链恒定区为Kappa,其氨基酸序列为SEQ ID No.11,核苷酸序列为SEQ ID No.14。
试验分为六组,分别为中和抗体P2C-1F11和DHA、中和抗体P2C-1F11和EDPs、中和抗体P2C-1F11和DMSO;中和抗体P2B-1G5和DHA、中和抗体P2B-1G5和EDPs、中和抗体P2B-1G5和DMSO。
将中和抗体从1.825 μg/mL三倍梯度稀释六个浓度,将七个浓度的中和抗体(100μL)分别与48 μL SARS-CoV-2假病毒(1×103 FFU)、2 μL DHA(5 μg/mL)混合并在37℃下孵育1hr,然后加入100 μL Vero细胞液(含1.5×104个细胞),并在37℃下培养24 hr。24 hr后,用opera Phoenix读取每个孔内的GFP阳性细胞数。以不加抗体的对照组为参比,使用Reed-Muench方法计算病毒感染50%抑制率的抗体浓度即为IC50。每组平行设计三个技术重复。
抗体与DHA或其衍生物添加浓度、添加量及质量比值如图7所示,中和抗体IC50测定数据如图8所示。
以上对本发明进行了详述。对于本领域技术人员来说,在不脱离本发明的宗旨和范围,以及无需进行不必要的实验情况下,可在等同参数、浓度和条件下,在较宽范围内实施本发明。虽然本发明给出了特殊的实施例,应该理解为,可以对本发明作进一步的改进。总之,按本发明的原理,本申请欲包括任何变更、用途或对本发明的改进,包括脱离了本申请中已公开范围,而用本领域已知的常规技术进行的改变。
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aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 360
ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 420
gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 480
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 540
agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 600
gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 660
aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 720
ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 780
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 840
ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 900
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 960
cagaagagcc tctccctgtc tccgggtaaa 990
<210> 13
<211> 318
<212> DNA
<213> 智人(Homo sapiens)
<400> 13
ggtcagccca aggctgcccc ctcggtcact ctgttcccac cctcgagtga ggagcttcaa 60
gccaacaagg ccacactggt gtgtctcata agtgacttct acccgggagc cgtgacagtg 120
gcctggaagg cagatagcag ccccgtcaag gcgggagtgg agaccaccac accctccaaa 180
caaagcaaca acaagtacgc ggccagcagc tacctgagcc tgacgcctga gcagtggaag 240
tcccacagaa gctacagctg ccaggtcacg catgaaggga gcaccgtgga gaagacagtg 300
gcccctacag aatgttca 318
<210> 14
<211> 321
<212> DNA
<213> 智人(Homo sapiens)
<400> 14
cgtacggtgg ctgcaccatc tgtcttcatc ttcccgccat ctgatgagca gttgaaatct 60
ggaactgcct ctgttgtgtg cctgctgaat aacttctacc ccagagaagc caaagtgcag 120
tggaaggtgg acaacgccct gcagagcgga aacagccagg aaagcgtgac agagcaggat 180
tccaaggatt ccacatacag cctgagcagc acactgacac tgtccaaggc cgactacgag 240
aagcacaagg tgtacgcctg cgaagtgaca caccagggac tgtcctcccc tgtgacaaag 300
agcttcaaca gaggagaatg c 321
Claims (3)
1.DHA环氧化物在制备增强抗冠状病毒的抗体对冠状病毒的抗病毒活性的产品中的应用;
所述冠状病毒为SARS-CoV-2。
2.根据权利要求1所述的应用,其特征在于:所述抗冠状病毒的抗体为P2C-1F11或P2B-1G5,
所述P2C-1F11的重链可变区(VH)的氨基酸序列是SEQ ID No.1,轻链可变区(VL)的氨基酸序列为SEQ ID No.2;重链恒定区为人IgG1,其氨基酸序列为SEQ ID No.9,轻链恒定区为Kappa,其氨基酸序列为SEQ ID No.11;
所述P2B-1G5的重链可变区(VH)的氨基酸序列是SEQ ID No.3,轻链可变区(VL)的氨基酸序列为SEQ ID No.5;重链恒定区为人IgG1,其氨基酸序列为SEQ ID No.9,轻链恒定区为lambda,其氨基酸序列为SEQ ID No.10。
3.冠状病毒抑制剂,其特征在于:所述冠状病毒抑制剂包括M1和M2,所述M1为DHA环氧化物,所述M2为抗冠状病毒的抗体;
所述抗冠状病毒的抗体与DHA环氧化物的质量比为0.075:1-2.43:1;
所述冠状病毒属病毒为SARS-CoV-2。
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Non-Patent Citations (2)
Title |
---|
Pharmaconutrition strategy to resolve SARS-CoV-2-induced inflammatory cytokine storm in non-alcoholic fatty liver disease:Omega-3 long-chain polyunsaturated fatty acids;Shanmugam M Jeyakumar等;《World Journal of Clinical Cases》;20211106;第9卷(第31期);9333-9349 * |
Shanmugam M Jeyakumar等.Pharmaconutrition strategy to resolve SARS-CoV-2-induced inflammatory cytokine storm in non-alcoholic fatty liver disease:Omega-3 long-chain polyunsaturated fatty acids.《World Journal of Clinical Cases》.2021,第9卷(第31期),9333-9349. * |
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