CN116492352A - ASGR1竞争结合剂在制备抑制SARS-CoV-2感染宿主细胞的制剂中的用途 - Google Patents
ASGR1竞争结合剂在制备抑制SARS-CoV-2感染宿主细胞的制剂中的用途 Download PDFInfo
- Publication number
- CN116492352A CN116492352A CN202210065284.7A CN202210065284A CN116492352A CN 116492352 A CN116492352 A CN 116492352A CN 202210065284 A CN202210065284 A CN 202210065284A CN 116492352 A CN116492352 A CN 116492352A
- Authority
- CN
- China
- Prior art keywords
- asgr1
- infection
- cov
- cells
- sars
- 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.)
- Pending
Links
- 101000785944 Homo sapiens Asialoglycoprotein receptor 1 Proteins 0.000 title claims abstract description 28
- 208000025721 COVID-19 Diseases 0.000 title claims abstract description 23
- 102100026292 Asialoglycoprotein receptor 1 Human genes 0.000 title claims abstract description 19
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 13
- 239000011230 binding agent Substances 0.000 title claims abstract description 10
- 230000009137 competitive binding Effects 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 208000037847 SARS-CoV-2-infection Diseases 0.000 title description 10
- 241001678559 COVID-19 virus Species 0.000 claims abstract description 41
- 229930182830 galactose Natural products 0.000 claims abstract description 33
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 claims abstract description 32
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims abstract description 32
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims abstract description 32
- 230000000694 effects Effects 0.000 claims abstract description 19
- 210000005229 liver cell Anatomy 0.000 claims description 42
- 210000004027 cell Anatomy 0.000 claims description 37
- 208000015181 infectious disease Diseases 0.000 claims description 23
- 230000027455 binding Effects 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 4
- 210000002919 epithelial cell Anatomy 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 210000002540 macrophage Anatomy 0.000 claims description 2
- 210000005087 mononuclear cell Anatomy 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 15
- 239000000126 substance Substances 0.000 abstract description 13
- 229940079593 drug Drugs 0.000 abstract description 7
- 238000002474 experimental method Methods 0.000 abstract description 7
- 241001112090 Pseudovirus Species 0.000 description 18
- 108060001084 Luciferase Proteins 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 8
- 238000002965 ELISA Methods 0.000 description 6
- 239000005089 Luciferase Substances 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 4
- 239000013592 cell lysate Substances 0.000 description 4
- 241000711573 Coronaviridae Species 0.000 description 3
- 108700008625 Reporter Genes Proteins 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229940126585 therapeutic drug Drugs 0.000 description 3
- HBZBAMXERPYTFS-SECBINFHSA-N (4S)-2-(6,7-dihydro-5H-pyrrolo[3,2-f][1,3]benzothiazol-2-yl)-4,5-dihydro-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)[C@H]1CSC(=N1)c1nc2cc3CCNc3cc2s1 HBZBAMXERPYTFS-SECBINFHSA-N 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 229940125645 monoclonal antibody drug Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229940126586 small molecule drug Drugs 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 102000053723 Angiotensin-converting enzyme 2 Human genes 0.000 description 1
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 description 1
- 101150075175 Asgr1 gene Proteins 0.000 description 1
- 108091033409 CRISPR Proteins 0.000 description 1
- 238000010354 CRISPR gene editing Methods 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明属于医药技术领域,及ASGR1竞争结合剂的新的药用用途,具体涉及一组用于阻碍2019新型冠状病毒通过ASGR1蛋白感染宿主细胞的化学药物,尤其涉及所述化学药物在制备抑制SARS‑CoV‑2感染宿主细胞的制剂中的用途,所述的ASGR1竞争结合剂是半乳糖和半乳糖胺。本发明经试验显示,所述化学药物具有抗Covid‑19感染的作用,该类药物可与Covid‑19潜在受体ASGR1结合,从而阻碍Covid‑19通过ASGR1进入宿主细胞,进而抑制Covid‑19感染。
Description
技术领域
本发明属于医药技术领域,涉及ASGR1竞争结合剂的新的药用用途,具体涉及一组用于阻碍2019新型冠状病毒通过ASGR1蛋白感染宿主细胞的化学药物,尤其涉及所述化学药物在制备抑制SARS-CoV-2感染宿主细胞的制剂中的用途,所述的ASGR1竞争结合剂化合物通过结合宿主ASGR1受体,阻碍SARS-CoV-2感染宿主细胞。
背景技术
据报道,由2019新型冠状病毒(2019-nCoV)感染宿主可引起新型冠状病毒肺炎(Corona Virus Disease 2019,COVID-19),临床实践显示,新型冠状病毒肺炎感染后的常见症状包括呼吸道症状、发热、咳嗽、气促和呼吸困难等。除此以外,还有研究发现,除了呼吸系统,2019新型冠状病毒还能感染脑,心脏,肾脏,肝脏等多个低表达,甚至不表达ACE2受体的组织。本申请研究团队在前期研究中,通过CRISPR激活型全基因组文库筛选,发现了新的2019新型冠状病毒感染受体-ASGR1,并证明2019新型冠状病毒能够通过ASGR1感染宿主肝脏细胞。
目前,2019新型冠状病毒治疗药物主要包括单克隆抗体药物和小分子药物。单克隆抗体药物虽然有一定的临床治疗效果,但是存在生产,保存,运输不便,价格昂贵等局限,并且由于2019新型冠状病毒属于RNA病毒,突变率高,容易导致免疫逃逸。目前的小分子药物显示了一定的疗效但成本较高。因此研发新型的2019新型冠状病毒治疗药物,增加新冠患者的治疗药物选择,是目前本领域亟待解决的问题。
现有技术公开了ASGR1蛋白是一种表达在细胞表面的膜蛋白,并且该蛋白可以作为半乳糖的运输蛋白,因此半乳糖和半乳糖胺可以与ASGR1结合,进而与 2019新型冠状病毒竞争ASGR1受体,阻碍2019新型冠状病毒通过ASGR1受体感染宿主细胞。迄今为止,有关半乳糖和半乳糖胺抗2019新型冠状病毒感染宿主细胞的作用尚未见报道。
基于现有技术的现状,本申请的发明人拟提供一组用于阻碍2019新型冠状病毒通过ASGR1蛋白感染宿主细胞的化学药物。
发明内容
本发明的目的是基于现有技术的现状,提供一组用于阻碍2019新型冠状病毒通过ASGR1蛋白感染宿主细胞的化学药物。该类化学药物属于ASGR1结合竞争剂。本发明尤其涉及所述化学药物在制备抑制SARS-CoV-2感染宿主细胞的制剂中的用途,所述的ASGR1竞争结合剂化合物通过结合宿主ASGR1受体,阻碍 SARS-CoV-2感染宿主细胞。
具体的,
本发明所述的化学药物是一类可抑制Covid-19感染细胞的化学药物半乳糖和半乳糖胺。本发明所用的半乳糖和半乳糖胺由国药集团提供,均溶于PBS(购自 Gbico),储存浓度500mM。
本发明中,半乳糖和半乳糖胺可以与Covid-19受体ASGR1蛋白结合。
本发明中,半乳糖和半乳糖胺能够阻碍Covid-19与受体ASGR1结合感染细胞的作用。
本发明中,所述的细胞属于人上皮细胞,单个核细胞,人巨噬细胞,人肝脏细胞等等。
本发明所用主要试剂材料如下:
本发明使用的原代人肝脏细胞是从Lonza公司获得。所使用的人肝脏永生化细胞系THLE-2来源于ATCC细胞库。
本申请基于目前的研究中,ASGR1能够通过结合半乳糖和半乳糖胺,从而阻止2019新型冠状病毒通过ASGR1受体感染宿主细胞。为了证实该类化学药物对 2019新型冠状病毒感染宿主细胞的抑制作用,本发明的技术方案如下所述。
本发明进行了半乳糖和半乳糖胺在人原代肝脏细胞和人永生化肝细胞系 THLE-2中抑制2019新型冠状病毒感染宿主细胞实验,
本发明的一个实施例中,进行了不同时间处理的半乳糖和半乳糖胺在人原代肝脏细胞和人永生化肝细胞系THLE-2中具有抗SARS-CoV-2假病毒感染的作用。
本发明的另一个实施例中,进行了不同浓度处理的半乳糖和半乳糖胺在人原代肝脏细胞和人永生化肝细胞系THLE-2中具有抗SARS-CoV-2假病毒感染的作用。
更具体的,
本发明以50mM浓度的半乳糖和半乳糖胺人原代肝脏细胞和人永生化肝细胞系THLE-2,分别处理0,1,2,4,8,12h后,使用带有荧光素酶报告基因的SARS-CoV-2 假病毒感染人原代肝脏细胞和人永生化肝细胞系THLE-2,感染12h后去除上清,补加完全培养基继续培养48h,收集细胞,通过荧光素酶基因报告实验检测半乳糖和半乳糖胺抑制SARS-CoV-2假病毒感染人原代肝脏细胞和人永生化肝细胞系 THLE-2效率。
本发明以0nM,10nM,100nM,1mM,10mM,100mM浓度的半乳糖和半乳糖胺分别处理人原代肝脏细胞和人永生化肝细胞系THLE-2 6h,之后使用带有荧光素酶报告基因的SARS-CoV-2假病毒感染人原代肝脏细胞和人永生化肝细胞系THLE-2,感染12h后去除上清,补加完全培养基继续培养48h,收集细胞,通过荧光素酶基因报告实验检测半乳糖和半乳糖胺抑制SARS-CoV-2假病毒感染人原代肝脏细胞和人永生化肝细胞系THLE-2效率。
上述两组实验研究了半乳糖和半乳糖胺在人原代肝脏细胞和人永生化肝细胞系THLE-2中抗SARS-CoV-2感染的作用,结果显示,使用半乳糖或者半乳糖胺处理的细胞,SARS-CoV-2在不同浓度处理条件下,均能够显著降低SARS-CoV-2对人原代肝脏细胞或者人永生化肝细胞系THLE-2的感染效率,并且具有统计学显著差异性。本发明实验结果表明,半乳糖和半乳糖胺具有抗SARS-CoV-2感染的作用。
本发明所述化学药物半乳糖和半乳糖胺可用于制备抑制SARS-CoV-2感染宿主细胞的制剂,所述的化学药物半乳糖和半乳糖胺作为ASGR1竞争结合剂通过结合宿主ASGR1受体,阻碍SARS-CoV-2感染宿主细胞。
附图说明
图1,不同时间处理的半乳糖和半乳糖胺在健康人原代肝脏细胞和人永生化肝细胞系THLE-2中具有抗SARS-CoV-2假病毒感染的作用,荧光素酶报告基因实验检测SARS-CoV-2假病毒感染后不同时间点细胞中荧光素酶的活性。
图2,不同浓度处理的半乳糖和半乳糖胺在健康人原代肝脏细胞和人永生化肝细胞系THLE-2中具有抗SARS-CoV-2假病毒感染的作用。荧光素酶报告基因实验检测SARS-CoV-2假病毒感染后不同浓度处理的细胞中荧光素酶的活性。
具体实施方式
实施例1不同时间处理的半乳糖和半乳糖胺在人原代肝脏细胞和人永生化肝细胞系THLE-2中具有抗SARS-CoV-2假病毒感染的作用
在24孔板中每孔加入2×105个人原代肝脏细胞或者人永生化肝细胞系THLE-2,每孔加入0.5mL人原代肝脏细胞或者人永生化肝细胞系专用培养基,将1M的半乳糖和半乳糖胺与培养基1:20比例加入。药物分别处理0,1,2,4,8,12h后,更换完全培养基。在上清中加入10μL的SARS-CoV-2假病毒(MOI=30)感染细胞。感染12h去除含有SARS-CoV-2假病毒的上清。病毒感染后48h收集细胞,加入 500μL细胞裂解液裂解细胞。在白色酶标板中每孔加入100μL的细胞裂解液,再加入50μL的荧光素酶底物,摇床混匀5min。将混匀好的酶标板放入酶标仪中,测定450nm处的发光值。将未处理,仅用SARS-CoV-2假病毒感染组的发光值归一,分别计算不同处理时间组的细胞SARS-CoV-2假病毒感染效率。
结果显示,使用半乳糖或者半乳糖胺处理的细胞,SARS-CoV-2在不同处理时间条件下,均能够显著降低SARS-CoV-2对人原代肝脏细胞或者人永生化肝细胞系 THLE-2的感染效率,并且具有统计学显著差异性。本发明结果提示,半乳糖和半乳糖胺具有抗SARS-CoV-2感染的作用。
实施例2不同浓度处理的半乳糖和半乳糖胺在人原代肝脏细胞和人永生化肝细胞系THLE-2中具有抗SARS-CoV-2假病毒感染的作用。
在24孔板中每孔加入2×105个人原代肝脏细胞或者人永生化肝细胞系THLE-2,每孔加入0.5mL人原代肝脏细胞或者人永生化肝细胞系专用培养基,将0nM,200 nM,2mM,20mM,200mM,2M的半乳糖和半乳糖胺与培养基1:20比例加入处理6 h后,更换完全培养基。在上清中加入10μL的SARS-CoV-2假病毒(MOI=30)感染细胞。感染12h去除含有SARS-CoV-2假病毒的上清。病毒感染后48h收集细胞,加入500μL细胞裂解液裂解细胞。在白色酶标板中每孔加入100μL的细胞裂解液,再加入50μL的荧光素酶底物,摇床混匀5min。将混匀好的酶标板放入酶标仪中,测定450nm处的发光值。将未处理,仅用SARS-CoV-2假病毒感染组的发光值归一,分别计算不同浓度处理组的细胞SARS-CoV-2假病毒感染效率。
结果显示,使用半乳糖或者半乳糖胺处理的细胞,SARS-CoV-2在不同浓度处理条件下,均能够显著降低SARS-CoV-2对人原代肝脏细胞或者人永生化肝细胞系 THLE-2的感染效率,并且具有统计学显著差异性。本发明结果提示,半乳糖和半乳糖胺具有抗SARS-CoV-2感染的作用。
Claims (4)
1.ASGR1竞争结合剂在制备抑制SARS-CoV-2感染宿主细胞的制剂中的用途,所述的ASGR1竞争结合剂是半乳糖和半乳糖胺。
2.按权利要求1所述的用途,其特征在于,所述的半乳糖和半乳糖胺能与Covid-19受体ASGR1蛋白结合。
3.按权利要求1所述的用途,其特征在于,所述的半乳糖和半乳糖胺能阻碍Covid-19与受体ASGR1结合感染细胞的作用。
4.按权利要求1所述的用途,其特征在于,所述的细胞属人上皮细胞,单个核细胞,人巨噬细胞或人肝脏细胞。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210065284.7A CN116492352A (zh) | 2022-01-18 | 2022-01-18 | ASGR1竞争结合剂在制备抑制SARS-CoV-2感染宿主细胞的制剂中的用途 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210065284.7A CN116492352A (zh) | 2022-01-18 | 2022-01-18 | ASGR1竞争结合剂在制备抑制SARS-CoV-2感染宿主细胞的制剂中的用途 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116492352A true CN116492352A (zh) | 2023-07-28 |
Family
ID=87317158
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210065284.7A Pending CN116492352A (zh) | 2022-01-18 | 2022-01-18 | ASGR1竞争结合剂在制备抑制SARS-CoV-2感染宿主细胞的制剂中的用途 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116492352A (zh) |
-
2022
- 2022-01-18 CN CN202210065284.7A patent/CN116492352A/zh active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Cao et al. | Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence | |
Sohail et al. | Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection | |
Sun et al. | Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3Tyr705 phosphorylation | |
WO2022184056A1 (zh) | 与SARS-CoV-2刺突蛋白特异性结合的多肽、多肽组合物及其制备方法与应用 | |
Aleebrahim-Dehkordi et al. | Acute kidney injury in COVID-19; a review on current knowledge. | |
CN111402968A (zh) | 基于分子模拟发现山柰酚在covid-19病毒中的新用途 | |
Geng et al. | Development of an attenuated tat protein as a highly-effective agent to specifically activate HIV-1 latency | |
Sakuragi | Morphogenesis of the infectious HIV-1 virion | |
Starshinova et al. | Efficacy of different types of therapy for COVID-19: A comprehensive review | |
Jiang et al. | Antibacterial properties and efficacy of a novel SPLUNC1-derived antimicrobial peptide, α4-short, in a murine model of respiratory infection | |
Xiao et al. | Pectolinarigenin prevents bone loss in ovariectomized mice and inhibits RANKL‐induced osteoclastogenesis via blocking activation of MAPK and NFATc1 signaling | |
Srivastava et al. | Silybin B and cianidanol inhibit Mpro and spike protein of SARS-CoV-2: Evidence from in silico molecular docking studies | |
WO2022246873A1 (zh) | 一种抗SARS-CoV-2的药物及应用 | |
Jana et al. | Targeting an evolutionarily conserved “ELL” motif in spike protein to identify a small molecule fusion inhibitor against SARS-CoV-2 | |
Xu et al. | Roles of inflammasomes in viral myocarditis | |
WO2004060360A1 (de) | Verwendung von wirksubstanzen zur prophylaxe und/oder therapie von viruserkrankungen | |
CN116492352A (zh) | ASGR1竞争结合剂在制备抑制SARS-CoV-2感染宿主细胞的制剂中的用途 | |
Monticone et al. | Demethyl fruticulin A (SCO‐1) causes apoptosis by inducing reactive oxygen species in mitochondria | |
CN114989263B (zh) | 与SARS-CoV-2刺突蛋白特异性结合的多肽KVp-N及其制备方法与应用 | |
CN114989255B (zh) | 与SARS-CoV-2刺突蛋白特异性结合的多肽KVp-R及其制备方法与应用 | |
CN114989245B (zh) | 与SARS-CoV-2刺突蛋白特异性结合的多肽KVp-C及其制备方法与应用 | |
CN113288892A (zh) | 聚adp核糖聚合酶抑制剂在抗冠状病毒中的应用 | |
CN114989264B (zh) | 与SARS-CoV-2刺突蛋白特异性结合的多肽组合物及其制备方法与应用 | |
Wang et al. | Utilizing nanozymes for combating COVID-19: advancements in diagnostics, treatments, and preventative measures | |
CN116098893B (zh) | 化合物Thapsigargin在制备预防或治疗猪流行性腹泻药物中的应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication |