CN111402968B - 基于分子模拟发现山柰酚在covid-19病毒中的新用途 - Google Patents
基于分子模拟发现山柰酚在covid-19病毒中的新用途 Download PDFInfo
- Publication number
- CN111402968B CN111402968B CN202010247402.7A CN202010247402A CN111402968B CN 111402968 B CN111402968 B CN 111402968B CN 202010247402 A CN202010247402 A CN 202010247402A CN 111402968 B CN111402968 B CN 111402968B
- Authority
- CN
- China
- Prior art keywords
- kaempferol
- covid
- virus
- novel coronavirus
- molecular simulation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- IYRMWMYZSQPJKC-UHFFFAOYSA-N kaempferol Chemical compound C1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 IYRMWMYZSQPJKC-UHFFFAOYSA-N 0.000 title claims abstract description 58
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 title claims abstract description 31
- UBSCDKPKWHYZNX-UHFFFAOYSA-N Demethoxycapillarisin Natural products C1=CC(O)=CC=C1OC1=CC(=O)C2=C(O)C=C(O)C=C2O1 UBSCDKPKWHYZNX-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 235000008777 kaempferol Nutrition 0.000 title claims abstract description 29
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 241001678559 COVID-19 virus Species 0.000 title claims abstract description 11
- 238000012900 molecular simulation Methods 0.000 title claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 21
- 208000025721 COVID-19 Diseases 0.000 claims abstract description 13
- 241000711573 Coronaviridae Species 0.000 claims abstract description 11
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 11
- 230000005764 inhibitory process Effects 0.000 claims abstract description 10
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 10
- 230000000694 effects Effects 0.000 claims abstract description 8
- 229940079593 drug Drugs 0.000 claims description 11
- 238000003032 molecular docking Methods 0.000 claims description 10
- 238000003041 virtual screening Methods 0.000 claims description 7
- 101800000535 3C-like proteinase Proteins 0.000 claims description 6
- 101800002396 3C-like proteinase nsp5 Proteins 0.000 claims description 6
- 101100338269 Caenorhabditis elegans his-41 gene Proteins 0.000 claims description 3
- 230000000120 cytopathologic effect Effects 0.000 abstract description 11
- 238000002474 experimental method Methods 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 108091005804 Peptidases Proteins 0.000 abstract description 2
- 102000035195 Peptidases Human genes 0.000 abstract description 2
- 238000004458 analytical method Methods 0.000 abstract description 2
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 235000019833 protease Nutrition 0.000 abstract 1
- 241000700605 Viruses Species 0.000 description 9
- 150000003384 small molecules Chemical class 0.000 description 6
- 241000315672 SARS coronavirus Species 0.000 description 5
- 101800000504 3C-like protease Proteins 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 231100000491 EC50 Toxicity 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- 231100000645 Reed–Muench method Toxicity 0.000 description 2
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000001503 joint Anatomy 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- JMGZEFIQIZZSBH-UHFFFAOYSA-N Bioquercetin Natural products CC1OC(OCC(O)C2OC(OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5)C(O)C2O)C(O)C(O)C1O JMGZEFIQIZZSBH-UHFFFAOYSA-N 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 description 1
- 206010035737 Pneumonia viral Diseases 0.000 description 1
- 108010076039 Polyproteins Proteins 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- 108010055591 SARS coronavirus 3C-like protease Proteins 0.000 description 1
- 241001174051 Thesium arvense Species 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000002832 anti-viral assay Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- IVTMALDHFAHOGL-UHFFFAOYSA-N eriodictyol 7-O-rutinoside Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C=C3C(C(C(O)=C(O3)C=3C=C(O)C(O)=CC=3)=O)=C(O)C=2)O1 IVTMALDHFAHOGL-UHFFFAOYSA-N 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- -1 flavonoid compounds Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- IQPNAANSBPBGFQ-UHFFFAOYSA-N luteolin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C(O)=C1 IQPNAANSBPBGFQ-UHFFFAOYSA-N 0.000 description 1
- LRDGATPGVJTWLJ-UHFFFAOYSA-N luteolin Natural products OC1=CC(O)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 LRDGATPGVJTWLJ-UHFFFAOYSA-N 0.000 description 1
- 235000009498 luteolin Nutrition 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- FDRQPMVGJOQVTL-UHFFFAOYSA-N quercetin rutinoside Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 FDRQPMVGJOQVTL-UHFFFAOYSA-N 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 235000005493 rutin Nutrition 0.000 description 1
- IKGXIBQEEMLURG-BKUODXTLSA-N rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 description 1
- ALABRVAAKCSLSC-UHFFFAOYSA-N rutin Natural products CC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5 ALABRVAAKCSLSC-UHFFFAOYSA-N 0.000 description 1
- 229960004555 rutoside Drugs 0.000 description 1
- 238000000547 structure data Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 208000009421 viral pneumonia Diseases 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16C—COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
- G16C20/00—Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
- G16C20/50—Molecular design, e.g. of drugs
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Urology & Nephrology (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Cell Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Bioinformatics & Computational Biology (AREA)
- Computing Systems (AREA)
- Theoretical Computer Science (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及基于分子模拟发现山柰酚在COVID‑19病毒中的新用途，发明人以COVID‑19的3CL主蛋白酶为靶标蛋白，从含有57278个中药小分子TCM的数据库中，虚拟筛选出了化合物山柰酚，通过山柰酚在细胞水平的抗新型冠状病毒实验，发明人发现山柰酚在62.50‑125.00µg/ml的浓度范围内对新型冠状病毒感染Vero E6细胞致细胞病变具有显著的抑制作用，这一发现从治疗靶标分析角度为中医药抗新型冠状病毒的科学性和潜在疗效提供了佐证。
Description
技术领域
本发明涉及生物技术领域，具体涉及基于分子模拟发现山柰酚在COVID-19病毒中的新用途。
背景技术
2019年12月，一种新型冠状病毒（COVID-19,又名2019-nCoV）在一批患者中被发现。患者表现出类似于中东呼吸综合征冠状病毒（MERS-CoV）和严重急性呼吸综合征冠状病毒（SARS-CoV）的病毒性肺炎症状。目前尚未有药物被批准专门用于COVID-19感染。随着COVID-19在世界范围持续蔓延，研发广谱抗冠状病毒药物和疫苗成为全球公共卫生、医学界、科研界的一个重大挑战。
冠状病毒主蛋白酶（Mpro，又叫3CLpro）是一种蛋白水解酶，可以水解加工复制酶前体多聚蛋白，并释放病毒RNA复制所需的聚合酶与解螺旋酶，是病毒复制过程中的关键步骤。3CLpro在病毒生命周期中的重要作用使其成为开发广谱抗冠状病毒药物的重要靶标蛋白。
近期，饶子和团队解析了COVID-19的3CL主蛋白酶 (COVID-19 3CLpro)的晶体结构（PDB ID：6LU7）。其活性位点结构以及基因序列与SARS-CoV 3CLpro 的非常相近，说明二者可能有相似的抑制机制。发明人曾基于SARS冠状病毒主蛋白酶（SARS-CoV 3CLpro）的蛋白活性位点设计了一种八肽AVLQSGFR（专利申请号200410018679.3，名称为“一种抑制冠状病毒的多肽及其衍生物”），并证明了计算机辅助虚拟筛选出的八肽制剂对SARS病毒有一定的抑制作用。相关筛选流程和实验方法为本发明的研究技术基础。
山柰酚（kaempferol）又名百蕊草素Ⅲ，属于黄酮类化合物，大量临床研究表明，其具有抗炎、抗氧化、抗菌等广泛的药理作用。具体结构如下：
山柰酚是否可以作为抗COVID-19病毒药物，对抗COVID-19病毒是否能起到有效作用，目前还尚未有文献提及。
发明内容
本发明的目的在于提供基于分子模拟发现山柰酚在COVID-19病毒中的新用途，以COVID-19 3CL主蛋白酶为靶标蛋白，通过药物虚拟筛选得到山柰酚，并用实验证明其对COVID-19感染细胞的致细胞病变效应具有显著的抑制作用。
为了实现上述目的，本发明提供的技术方案如下：
基于分子模拟发现山柰酚在COVID-19病毒中的新用途。
发明人进行了以下实验：
1、以中药小分子TCM数据库为对接配体库进行虚拟筛选。
2、根据对接得分进行排序并获得前5名化合物的小分子结构。
3、选取山柰酚进行抗病毒实验验证，评价其对COVID-19感染的细胞病变作用。
其中，虚拟筛选以COVID-19的3CL主蛋白酶为靶标蛋白，HIS41和CYS145为对接活性口袋。
其中，化合物山柰酚从中药小分子TCM数据库中虚拟筛选而出。
其中，山柰酚在62.50-125.00µg/ml的浓度范围内对新型冠状病毒感染Vero E6细胞致细胞病变具有显著的抑制作用。
本发明的有益效果是：发明人通过虚拟筛选和抗病毒实验，首次发现了山柰酚在62.50-125.00µg/ml的浓度范围内对COVID-19感染Vero E6细胞的致细胞病变具有显著的抑制作用。这一发现从治疗靶标分析角度为中医药抗新型冠状病毒的科学性和潜在疗效提供了佐证。
附图说明
图1为药物筛选前五名化合物的二维描述及其对接得分图。
图2为山柰酚对COVID-19药效检测结果图。
具体实施方式
以下结合附图和具体实施例对本发明作具体的介绍。
本发明所用到的虚拟筛选软件为SAMM(Shanghai Molecular Modelling)。2019-nCoV受试药物为山柰酚粉末，所用到的细胞为VeroE6细胞，由广州呼吸健康研究院呼吸疾病国家重点实验室病毒室保存，病毒为SARS-COV-2，滴度为TCID50 = 10-6/100 μL，由广州海关技术中心BSL-3实验室（呼吸疾病国家重点实验室高致病病原微生物研究室）-80℃保存，使用病毒滴度为100TCID50。
实施例1，虚拟筛选。实验以COVID-19 3CLpro为靶标蛋白（PDB ID：6LU7），其三维结构数据来源于PDB数据库。配体数据来源于 TCM Database@Taiwa (http://tcm.cmu.edu.)获取的中药小分子和发明人自建的中药化学数据库，进行对接的中药小分子数共计 57278 个。对接前先按照Lipinski类药五规则进行初步筛选，所得小分子需满足以下五个条件条件：（1）分子量小于500；（2）氢键给体数目小于5；（3）氢键受体数目小于10；（4）脂水分配系数小于5；（5）可旋转键的数量不超过10个。对接使用SAMM软件，对接前用对靶标蛋白进行预处理，包括蛋白质加氢、计算电荷、添加原子类型。对接参考发明人已设计的八肽抑制剂结合SARS-Cov 3CLpro的结合位点，以HIS41和CYS145作为对接活性口袋，据此展开基于结构的药物筛选。 最终，根据37800个化合物的对接分进行排序，筛选出了前五名化合物：芦丁、山柰酚、木犀草素、槲皮素和长春花碱，如图1所示。
实施例2，山柰酚抗病毒实验。实验设计如表1所示，无菌96孔培养板,每孔加入100μL浓度为2×105 cells/mL VeroE6细胞，37℃、5% CO2培养箱培养24小时；培养板实验组和病毒对照组加入100 TCID50病毒液100 μL/孔，37℃、5% CO2培养箱吸附2小时；2小时后，弃去96孔培养板中细胞培养液；山柰酚稀释成125μM、62.5μM和31.25μM三个不同浓度，每个浓度3个复孔，100μL/孔加入上述药液；细胞37℃、5% C02孵箱孵育3-4天；光学显微镜下观察细胞病变（CPE），细胞出现病变程度按以下6级标准记录：“-”无病变出现；“±”为细胞病变少于10%；“+”为细胞病变约25%；“+ +”为细胞病变约50%；“+ + +”为约75%的细胞出现病变：“+ + + +”为75%以上病变。采用Reed-Muench法或GraphPad Prism5.0计算半数有效浓度(IC50)。判断药效标准：具有50%的抑制病毒CPE的浓度视为有效浓度。以上实验操作均在BSL-3实验室内完成。
表1 实验分组及药物浓度
| 分组 | 药物 | 药物浓度（μM） |
| 实验组 | 山柰酚 | 125、62.5、31.25 |
| 病毒对照组 | COVID-19病毒液 | 100 TCID50/孔 |
| 细胞对照 | 培养基 |
通过观察细胞病变（CPE）并记录实验结果，采用Reed-Muench法或GraphPadPrism5.0计算半数有效浓度(IC50)，实验结果如表2和图2所示。
表2 山柰酚抗新型冠状病毒药效结果
| 药物浓度（μM） | 抑制率（%） |
| 125.00 | 88.33±12.58 |
| 62.50 | 93.33±5.77 |
| 31.25 | 40.00±34.64 |
从表2和图2的实验结果可以看出山柰酚在62.50-125.00µg/ml的浓度范围内对新型冠状病毒感染Vero E6细胞致细胞病变具有显著的抑制作用。
Claims (1)
1.基于分子模拟发现山柰酚在COVID-19病毒中的新用途，其特征在于，虚拟筛选以COVID-19的3CL主蛋白酶为靶标蛋白，HIS41和CYS145为对接活性口袋，山柰酚在62.50-125.00μg/ml的浓度范围内对新型冠状病毒感染Vero E6细胞致细胞病变具有抑制作用，在药物浓度为62.5μM时对COVID-19病毒感染的Vero E6细胞的抑制率达93.33±5.77％。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010247402.7A CN111402968B (zh) | 2020-04-01 | 2020-04-01 | 基于分子模拟发现山柰酚在covid-19病毒中的新用途 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010247402.7A CN111402968B (zh) | 2020-04-01 | 2020-04-01 | 基于分子模拟发现山柰酚在covid-19病毒中的新用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111402968A CN111402968A (zh) | 2020-07-10 |
| CN111402968B true CN111402968B (zh) | 2023-11-03 |
Family
ID=71429335
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010247402.7A Active CN111402968B (zh) | 2020-04-01 | 2020-04-01 | 基于分子模拟发现山柰酚在covid-19病毒中的新用途 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111402968B (zh) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112063708A (zh) * | 2020-09-11 | 2020-12-11 | 成都中医药大学 | 一种从中药中筛选药物活性化合物的方法及作用剂 |
| CN112168899B (zh) * | 2020-09-30 | 2022-07-01 | 上海中医药大学 | 抑制冠状病毒3cl蛋白水解酶的藤茶提取物及其用途 |
| CN112525804B (zh) * | 2020-11-21 | 2022-07-22 | 烟台智医医药科技有限公司 | 全血细胞计数在预测SARS-CoV-2感染中的应用 |
| CN113230288A (zh) * | 2021-06-29 | 2021-08-10 | 安徽省森湶谷药业股份有限公司 | 百蕊草或百蕊草提取物或百蕊草萃取物作为新型冠状病毒治疗药物或抗病毒制剂用途 |
| CN113230289A (zh) * | 2021-07-01 | 2021-08-10 | 安徽省森湶谷药业股份有限公司 | 桑黄和百蕊草复方作为新型冠状病毒治疗药物或抗病毒制剂的用途 |
| CN116211966A (zh) * | 2021-12-04 | 2023-06-06 | 西北大学 | 植物提取物的用途、新型冠状病毒主蛋白酶抑制剂及筛选方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1472336A (zh) * | 2003-06-04 | 2004-02-04 | 中国科学院上海药物研究所 | Sars冠状病毒3cl蛋白酶三维结构模型与抗sars药物 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7166435B2 (en) * | 2001-08-06 | 2007-01-23 | The Quigley Corporation | Compositions and methods for reducing the transmissivity of illnesses |
-
2020
- 2020-04-01 CN CN202010247402.7A patent/CN111402968B/zh active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1472336A (zh) * | 2003-06-04 | 2004-02-04 | 中国科学院上海药物研究所 | Sars冠状病毒3cl蛋白酶三维结构模型与抗sars药物 |
Non-Patent Citations (7)
| Title |
|---|
| Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequistite conformational state for receptor binding;Miao Gui等;《Cell Search》;第27卷;全文 * |
| 中药抗病毒活性成分研究进展;陈鸿平;王福;尤强;申梦园;李泽娜;吴蓓;杨森给;陈林;刘友平;;中药与临床(第01期);全文 * |
| 刘川 ; 苏锦松 ; 李轩豪 ; 唐策 ; 刘悦 ; 张艺 ; .基于网络药理学和分子对接法筛选藏药五味沙棘散治疗新型冠状病毒肺炎（COVID-19）活性成分的研究.世界科学技术-中医药现代化.2020,(03),第632-641页. * |
| 刘川 等.基于网络药理学和分子对接法筛选藏药五味沙棘散治疗新型冠状病毒肺炎（COVID-19）活性成分的研究.《世界科学技术-中医药现代化》.2020,第第22卷卷(第第22卷期),第632-641页. * |
| 基于网络药理学和分子对接探讨痰热清注射液治疗新型冠状病毒肺炎(COVID-19)的机制;孔艺;吴红卫;陈永;赖莎;杨泽民;陈吉生;;中草药(第07期);全文 * |
| 沈浮 ; 付中应 ; 吴泳蓉 ; 邝高艳 ; 李玲 ; 朱恺民 ; 赵昱东 ; 夏雨 ; 陈苇 ; 郭垠梅 ; 赖庆来 ; .基于网络药理学及分子对接技术研究疏风解毒胶囊治疗新型冠状病毒肺炎的潜在靶标及机制.中医药导报.2020,(05),全文. * |
| 马青云 等.基于高通量分子对接虚拟筛选SARS-CoV-2 3CL水解酶中药小分子抑制剂及抗新型冠状病毒肺炎（COVID-19）的中药及其复方预测.《中草药》.2020,第第51卷卷(第第51卷期),第1397-1405页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111402968A (zh) | 2020-07-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111402968B (zh) | 基于分子模拟发现山柰酚在covid-19病毒中的新用途 | |
| Wu et al. | Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods | |
| Ye et al. | Network pharmacology, molecular docking integrated surface plasmon resonance technology reveals the mechanism of Toujie Quwen Granules against coronavirus disease 2019 pneumonia | |
| Citarella et al. | SARS-CoV-2 Mpro: a potential target for peptidomimetics and small-molecule inhibitors | |
| CN116236580B (zh) | 金诺芬等老药及其组合物在抗单正链rna病毒中的应用 | |
| CN113262224A (zh) | 奈非那韦在制备防治新冠肺炎药物中的应用 | |
| Laajala et al. | Therapeutic targets for enterovirus infections | |
| Panoutsopoulos | Conjunctivitis as a sentinel of SARS-CoV-2 infection: a need of revision for mild symptoms | |
| Mahrosh et al. | Computer‐Aided Prediction and Identification of Phytochemicals as Potential Drug Candidates against MERS‐CoV | |
| Yan et al. | Drug repositioning for hand, foot, and mouth disease | |
| Chen et al. | Recent progress in the development of potential drugs against SARS-CoV-2 | |
| Kandeel et al. | Antiviral drug discovery by targeting the SARS-CoV-2 polyprotein processing by inhibition of the main protease | |
| CN104887694A (zh) | 一种靶向非编码rna的反义寡核苷酸及其在制备抗流感病毒药物中的应用 | |
| Ghasemlou et al. | Exploration of potential inhibitors for SARS‐CoV‐2 Mpro considering its mutants via structure‐based drug design, molecular docking, MD simulations, MM/PBSA, and DFT calculations | |
| Valipour et al. | An overview on anti-COVID-19 drug achievements and challenges ahead | |
| CN113456657B (zh) | 糖基聚醚化合物在制备抗rna病毒药物中的用途 | |
| Zhao et al. | Multi-target mechanisms against coronaviruses of constituents from Chinese Dagang Tea revealed by experimental and docking studies | |
| Siddique et al. | Evidence and speculations: vaccines and therapeutic options for COVID-19 pandemic | |
| Kandeel | An overview of the recent progress in Middle East Respiratory Syndrome Coronavirus (MERS-CoV) drug discovery | |
| Miatmoko et al. | The Use of Azithromycin and Lopinavir-Ritonavir in the Treatment of COVID-19 | |
| Mishra et al. | Computational studies of drugs for possible action against Covid-19 infections | |
| CN113712976B (zh) | 小分子化合物肌醇六磷酸酯钠水合物在制备抗SARS-CoV-2药物中的应用 | |
| Chaudhury et al. | Case report on recovery from Japanese encephalitis virus infection by complementary use of phytolacca-mother tincture and in silico analysis | |
| Arif et al. | An overview of Covid-19 pandemic: immunology and Pharmacology | |
| CN114272244B (zh) | 恩曲替尼或其盐的新用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |