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Raltegravir

別名: MK-0518 中文名稱：拉替拉韋，雷特格韋

Raltegravir是一種有效的integrase (IN)抑制劑，作用于WT和S217Q PFV IN，在無細胞試驗中IC50分別為90 nM和40 nM。它對HIV-1 IN的選擇性比對其他相關Mg2+依賴性酶要高1000倍以上，如HCV聚合酶、HIV反轉錄酶、HIV RNaseH、人類α-, β-, γ-聚合酶。

Raltegravir Chemical Structure

Raltegravir Chemical Structure

CAS: 518048-05-0

規(guī)格 價格 庫存 購買數(shù)量
10mM (1mL in DMSO) 1722.95 現(xiàn)貨
5mg 983.46 現(xiàn)貨
10mg 1729.52 現(xiàn)貨
50mg 5494.35 現(xiàn)貨
200mg 10401.3 現(xiàn)貨
1g 13677.3 現(xiàn)貨
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Raltegravir相關產(chǎn)品

相關信號通路圖

Integrase Signaling Pathways

Integrase信號通路圖

細胞實驗數(shù)據(jù)示例

細胞系 實驗類型 給藥濃度 孵育時間 活性描述 文獻信息
U373-MAGI Antiviral assay 50 or 100 nM 72 hrs Antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as reduction in gag level at 50 or 100 nM measured at 72 hrs post infection by qPCR method 27117260
U373-MAGI Antiviral assay 50 or 100 nM 72 hrs Antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as reduction in U5-gag level at 50 or 100 nM measured at 72 hrs post infection by qPCR method 27117260
MT2 Antiviral assay 1 uM 30 hrs Antiviral activity against wild-type HIV1 NL4-3 infected infected in human MT2 cells assessed as reduction in HIV1 integrated DNA at 1 uM and measured after 30 hrs post infection by Alu-LTR PCR protocol based method 30996780
MT2 Antiviral assay 3 to 4 days Antiviral activity against HIV1 NL4-3 infected in human MT2 cells measured after 3 to 4 days by luciferase reporter gene assay, EC50 = 0.002 μM. 32081010
MT2 Antiviral assay 5 days Antiviral activity against HIV1 3B infected in human MT2 cells after 5 days by chemiluminescence in presence of fetal bovine serum, EC50 = 0.004 μM. 19285389
HOS Antiviral assay 3 hrs Antiviral activity against wild-type Human immunodeficiency virus 1 infected in HOS cells preincubated for 3 hrs followed by viral infection measured after 48 hrs by luciferase reporter gene assay, EC50 = 0.004 μM. 24471816
MT2 Antiviral assay 5 days Antiviral activity against HIV1 3B in MT2 cells after 5 days, EC50 = 0.006 μM. 18207398
MT4 Function assay 1 hr Inhibition of wild type HIV1 3B infected in human MT4 cells using cells pre-incubated with compound for 1 hr measured 4 days post viral infection by MTT assay, IC50 = 0.0062 μM. 22963135
MT4 Antiviral assay 48 to 72 hrs Antiviral activity against HIV1 infected in human MT4 cells expressing GFP incubated for 48 to 72 hrs in absence of 50% normal human serum by multiple round viral replication kinetics assay, IP = 0.009 μM. 26397965
HeLa Antiviral assay 48 hrs Antiviral activity against VSV-G pseudotyped HIV1 lentiviral particles infected in human HeLa cells incubated for 48 hrs by spectrofluorometry, IC50 = 0.01 μM. 22858300
cat FL-4 Antiviral assay 7 days Antiviral activity against Feline immunodeficiency virus infected in cat FL-4 cells assessed as inhibition of viral replication after 7 days by quantitative RT-PCR analysis, EC50 = 0.01 μM. 25702849
cat FL-4 Antiviral assay 7 days Antiviral activity against FIV infected in cat FL-4 cells assessed as reduction in viral RNA level measured after 7 days by qRT-PCR analysis, EC50 = 0.01 μM. 31395510
BL21(DE3) Function assay 1 hr Inhibition of recombinant HIV-1 integrase stand transfer activity expressed in Escherichia coli BL21(DE3) cells using 32P-labeled DNA substrate after 1 hr by densitometric analysis, IC50 = 0.013 μM. 26451771
MT4 Antiviral assay 5 days Antiviral activity against HIV1 3B infected in human MT4 cells incubated for 5 days by MTT assay, EC50 = 0.015 μM. 31324562
MT-4 Antiviral assay 5 days Antiviral activity against HIV1 3B/LAI infected in human MT-4 cells assessed as inhibition of virus-induced cytopathic effect measured survival after 5 days by MTT assay, EC50 = 0.016 μM. 24124919
HeLa-CD4-LTR-beta-gal Antiviral assay 1 day Antiviral activity against HIV-1 3B infected in human HeLa-CD4-LTR-beta-gal cells after 1 day by spectroscopic analysis, EC50 = 0.016 μM. 25629256
MT2 Antiviral assay 5 days Antiviral activity against HIV1 3B infected in human MT2 cells after 5 days by chemiluminescence in presence of human serum albumin, EC50 = 0.02 μM. 19285389
MT4 Antiviral assay 5 days Antiviral activity against HIV2 ROD infected in human MT4 cells incubated for 5 days by MTT assay, EC50 = 0.02 μM. 31324562
TZM-b1 Antiviral assay 1 hr Antiviral activity against HIV-1 NL4.3 infected in human TZM-b1 cells pretreated for 1 hr followed by viral infection measured after 2 days by CPRG assay, IC50 = 0.021 μM. 28408224
CEM-SS Antiviral assay 6 days Antiviral activity against HIV1 3B infected in human CEM-SS cells assessed as reduction of virus-induced cytopathic effect after 6 days by MTS assay, EC50 = 0.023 μM. 27283261
HeLa Antiviral assay 3 days Antiviral activity against HIV1 3B infected in human HeLa cells expressing CD4-LTR-beta-gal assessed as inhibition of viral replication after 3 days by reporter gene assay, EC50 = 0.0236 μM. 24684270
HeLa Antiviral assay 2 days Antiviral activity against HIV1 3B infected in human HeLa cells expressing CD4 assessed as inhibition of viral replication after 2 days by beta-galactosidase reporter gene assay, EC50 = 0.024 μM. 24124919
TZM-bl Antiviral assay 48 hrs Antiviral activity against Human immunodeficiency virus 1 infected in human TZM-bl cells assessed as inhibition of viral replication after 48 hrs by inverted microscopic analysis, EC50 = 0.025 μM. 22154762
MT4 Function assay 1 hr Inhibition of wild type HIV1 3B infected in human MT4 cells using cells pre-incubated with compound for 1 hr measured 4 days post viral infection in presence of 20 mg/ml HSA by MTT assay, IC50 = 0.029 μM. 22963135
P4R5 MAGI Antiviral assay 24 hrs Antiviral activity against HIV1 infected in CD4/CXCR4/CCR5 expressing human P4R5 MAGI cells preincubated with cells for 24 hrs followed by viral infection measured after 48 hrs by beta-galactosidase reporter gene assay, EC50 = 0.03 μM. 30031976
P4R5 Antiviral assay 24 hrs Antiviral activity against HIV1 infected in CD4/CXCR4/CCR5 expressing human P4R5 cells assessed as inhibition of viral replication preincubated with cells for 24 hrs followed by viral infection measured after 48 hrs by beta-galactosidase reporter gene ass, EC50 = 0.03 μM. 28525279
P4R5 Antiviral assay 24 hrs Antiviral activity against HIV1 infected in human P4R5 cells assessed as reduction in viral infection preincubated with cells for 24 hrs followed by viral infection measured after 48 hrs by fluorescence based beta-galactosidase reporter gene based MAGI as, EC50 = 0.03 μM. 29031062
P4R5 Antiviral assay 24 hrs Antiviral activity against HIV-1 infected in human P4R5 cells assessed as reduction in viral replication preincubated for 24 hrs followed by viral infection and measured after 48 hrs by MAGI assay, EC50 = 0.03 μM. 30739822
P4R5 Antiviral assay 24 hrs Antiviral activity against HIV1 infected in human P4R5 cells assessed as reduction of virus replication preincubated with cells for 24 hrs followed by viral infection for 48 hrs by 4-methylumbelliferylgalactoside-based MAGI assay, EC50 = 0.03 μM. 27283261
MT4 Antiviral assay 48 to 72 hrs Antiviral activity against HIV1 infected in human MT4 cells expressing GFP incubated for 48 to 72 hrs in presence of 50% normal human serum by multiple round viral replication kinetics assay, IP = 0.053 μM. 26397965
BL21(DE3) Function assay 1 hr Inhibition of LEDGF/p75-dependent full length HIV-1 integrase expressed in Escherichia coli BL21(DE3) cells preincubated for 1 hr further incubated for 90 mins with biotin-labeled donor DNA and target DNA by HTRF assay, IC50 = 0.058 μM. 31442684
HeLa-T4 Antiviral assay 48 hrs Antiviral activity against single-round HIV1 NLX.Lux-R harboring inactivating mutations in env, vpr and carries firefly luciferase gene in place of nef infected in human HeLa-T4 cells assessed as luciferase activity after 48 hrs by exogenous RT assay, EC50 = 0.077 μM. 21060108
TZM-bl Antiviral assay 48 hrs Antiviral activity against HIV-1 infected in human TZM-bl cells assessed as inhibition of viral replication for 48 hrs by bright-Glo luciferase assay, EC50 = 0.15 μM. 26487913
HOS Antiviral assay 3 hrs Antiviral activity against Human immunodeficiency virus 1 harboring integrase N155H mutant infected in HOS cells preincubated for 3 hrs followed by viral infection measured after 48 hrs by luciferase reporter gene assay, EC50 = 0.154 μM. 24471816
HOS Antiviral assay 3 hrs Antiviral activity against Human immunodeficiency virus 1 harboring integrase Y143R mutant infected in HOS cells preincubated for 3 hrs followed by viral infection measured after 48 hrs by luciferase reporter gene assay, EC50 = 0.162 μM. 24471816
TZM-bl Antiviral assay 1 hr Antiviral activity against HIV1 NL4.3 infected in human TZM-bl cells expressing CXCR4-tropic incubated for 1 hr prior to infection measured after 48 hrs by luciferase reporter gene assay, IC50 = 0.5 μM. 24291042
TZM-bl Antiviral assay 1 hr Antiviral activity against HIV1 NL4.3 infected in human TZM-bl cells expressing CXCR4-tropic incubated for 1 hr prior to infection measured after 48 hrs by luciferase reporter gene assay, IC50 = 0.50119 μM. 24291042
HeLa-T4 Antiviral assay 48 hrs Antiviral activity against single-round HIV1 NLX.Lux-R harboring inactivating mutations in env, vpr and carries firefly luciferase gene in place of nef infected in human HeLa-T4 cells assessed as luciferase activity after 48 hrs by exogenous RT assay, EC95 = 0.81 μM. 21060108
HOS Antiviral assay 3 hrs Antiviral activity against Human immunodeficiency virus 1 harboring integrase G140S/Q148H double mutant infected in HOS cells preincubated for 3 hrs followed by viral infection measured after 48 hrs by luciferase reporter gene assay, EC50 = 1.9 μM. 24471816
MT2 Antiviral assay 3 to 4 days Antiviral activity against HIV1 NL4-3 harboring G140S/Q148H mutant infected in human MT2 cells measured after 3 to 4 days by luciferase reporter gene assay, EC50 = 2.42 μM. 32081010
HeLaT4 Antiviral assay 24 hrs Antiviral activity against single-round HIV1 NLX.Lux-R harboring inactivating mutations in env, vpr and carries firefly luciferase gene in place of nef assessed as level of infection using human HeLaT4 cells pretreated for 24 hrs followed by exposed to vi, EC50 = 4.6 μM. 21060108
MT4 Cytotoxicity assay 5 days Cytotoxicity in mock-infected human MT4 cells assessed as reduction in cell viability incubated for 5 days by MTT assay, CC50 = 6.51 μM. 31324562
MT-4 Antiviral assay Antiviral activity against vesicular stomatitis virus G-pseudotyped Human immunodeficiency virus infected in human MT-4 cells assessed as inhibition of viral replication, EC50 = 0.002 μM. 18160521
MT-4 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT-4 cells assessed as inhibition of viral replication, EC50 = 0.0018 μM. 18160521
MT4 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT4 cells assessed as inhibition of viral replication, EC50 = 0.0014 μM. 18541726
MT-2 Antiviral assay Antiviral activity against HIV1 3B infected in human MT-2 cells by two fold dilution method in presence of 10% FBS, EC50 = 0.003 μM. 19104010
HOS Antiviral assay Antiviral activity against HIV1 harboring wild-type integrase infected in human HOS cells, EC50 = 0.004 μM. 21493066
MT-4 Antiviral assay Antiviral activity against HIV 1 RIN harboring integrase gene infected in MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.006 μM. 18378713
MT4 Antiviral assay Antiviral activity against HIV1 3B infected in human MT4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.006 μM. 24900718
MT4 Antiviral assay Antiviral activity against HIV-1 3B infected in human MT4 cells assessed as protection against virus-induced cytopathic effect by MTT assay, EC50 = 0.006 μM. 24793360
MT4 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT4 cells assessed as inhibition of virus induced cytopathic effect, EC50 = 0.0061 μM. 20479206
MT4 Antiviral assay Antiviral activity against HIV1 3B infected in human MT4 cells assessed as reduction of virus-induced cytopathogenicity by MTT assay, EC50 = 0.0064 μM. 19447621
MT-4 Antiviral assay Antiviral activity against HIV 1 NL4.3 harboring integrase L74M mutant infected in human MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.007 μM. 18378713
MT4 Antiviral assay Antiviral activity against HIV1 3B infected in human MT4 cells assessed as inhibition of viral-induced cytopathic effect by MTT assay, EC50 = 0.0078 μM. 28951095
MT-4 Antiviral assay Antiviral activity against HIV1 3B infected in human MT-4 cells by two fold dilution method in presence of 10% FBS, EC50 = 0.008 μM. 19104010
MT-4 Antiviral assay Antiviral activity against HIV 1 NL4.3 integrase S230N mutant infected in human MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.009 μM. 18378713
FL-4 Antiviral assay Antiviral activity against Feline immunodeficiency virus infected in cat FL-4 cells assessed as viral RNA production by RT-qPCR, EC50 = 0.00998 μM. 24813732
MT-4 Antiviral assay Antiviral activity against HIV 1 RIN harboring integrase gene infected in MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay after 20 passages selected in presence of compound, EC50 = 0.01 μM. 18378713
MT4 Antiviral assay Antiviral activity against HIV2 ROD 3B infected in human MT4 cells assessed as inhibition of viral-induced cytopathic effect by MTT assay, EC50 = 0.011 μM. 28951095
MT4 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in MT4 cells assessed as protection against virus-induced cytopathic effect measured 5 days post infection by MTT assay, EC50 = 0.0117 μM. 29940462
MT4 Antiviral assay Antiviral activity against HIV1 3B assessed as inhibition of viral-induced cytopathic effect in human MT4 cells, EC50 = 0.013 μM. 18417342
MT4 Antiviral assay Antiviral activity against HIV1 infected in human MT4 cells assessed as inhibition of virus-induced cytopathic effect, EC50 = 0.013 μM. 20630765
MT4 Antiviral assay Antiviral activity against HIV1 3B infected in human MT4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.013 μM. 21227550
MT-4 Antiviral assay Antiviral activity against HIV 1 NL4.3 integrase E92Q mutant infected in human MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.015 μM. 18378713
MT2 Antiviral assay Antiviral activity against HIV in MT2 cells in presence of 35 mg/mL human serum albumin, EC50 = 0.016 μM. 18207398
MT-2 Antiviral assay Antiviral activity against HIV1 3B infected in human MT-2 cells by two fold dilution method in presence of 10% FBS, HSA and alpha1-AGP, EC50 = 0.018 μM. 19104010
MT4 Antiviral assay Antiviral activity against HIV1 3B in human MT4 cells in presence of 10% heat-activated fetal bovine serum, IC95 = 0.019 μM. 18763751
HeLa-CD4-LTR-beta-gal Antiviral assay Antiviral activity against HIV-1 3B infected in human HeLa-CD4-LTR-beta-gal cells assessed as inhibition of viral replication by SpectraMax GEMINI-XS plate reader analysis, EC50 = 0.0236 μM. 25961960
MT-4 Antiviral assay Antiviral activity against HIV 1 RIN HIV 1 RIN harboring integrase gene infected in MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay after 40 passages selected in presence of compound, EC50 = 0.025 μM. 18378713
MT4 Antiviral assay Antiviral activity against HIV1 3B in human MT4 cells in presence of 50% normal human serum, IC95 = 0.031 μM. 18763751
MT-4 Antiviral assay Antiviral activity against HIV 1 RIN HIV 1 RIN harboring integrase gene infected in MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay after 60 passages selected in presence of compound, EC50 = 0.068 μM. 18378713
HeLaT4 Antiviral assay Antiviral activity against single-round HIV1 NLX.Lux-R harboring inactivating mutations in env, vpr and carries firefly luciferase gene in place of nef assessed as level of 2 mins magnetic nanopartials-medated infection in human HeLaT4 cells treated for 1, EC91 = 0.073 μM. 21060108
TZM-bl Antiviral assay Antiviral activity against HIV1 NL4.3 infected in human TZM-bl cells measured upto 24 hrs by bright Glo-luciferase reporter gene assay, IC50 = 0.16 μM. 31557609
CHO Function assay Inhibition of slow delayed inward rectifying potassium current (Iks) in Chinese Hamster Ovary (CHO) cells expressing hKvLQT1/hminK measured using IonWorks Quattro automated patch clamp platform, IC50 = 25.1189 μM. 25087753
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生物活性

產(chǎn)品描述 Raltegravir是一種有效的integrase (IN)抑制劑，作用于WT和S217Q PFV IN，在無細胞試驗中IC50分別為90 nM和40 nM。它對HIV-1 IN的選擇性比對其他相關Mg2+依賴性酶要高1000倍以上，如HCV聚合酶、HIV反轉錄酶、HIV RNaseH、人類α-, β-, γ-聚合酶。
特性 Raltegravir 是第一個被批準的人類免疫缺陷病毒1型（HIV-1）整合酶抑制劑。
靶點
Integrase (S217Q PFV) [1]
(Cell-free assay)		 Integrase (WT PFV) [1]
(Cell-free assay)
40 nM 90 nM
體外研究(In Vitro)
體外研究活性 PFV整合攜帶S217H替換的IN，之后對 Raltegravir 的敏感性降低10倍，IC50為900 nM。PFV IN 具有10% WT 活性，且被Raltegravir抑制，IC50為200 nM,說明與 WT IN相比，對整合酶（IN）鏈轉移抑制劑(INSTI)的敏感性降低約2倍。S217Q PFV IN 對 Raltegravir的敏感性至少與WT 酶相似。[1] Raltegravir由葡萄糖醛酸化，而不是肝臟代謝而來。Raltegravir 在體外作用于人類T 淋巴細胞培養(yǎng)物，有效作用于HIV-1，抑制達95%時濃度為31±20 nM。Raltegravir作用于 CEMx174細胞，也有效作用于HIV-2,IC95為6 nM。Raltegravir 代謝主要通過葡萄糖醛酸化。葡萄糖醛酸化酶的強誘導劑UGT1A1顯著降低 Raltegravir 濃度。Raltegravir 微弱抑制肝細胞色素 P450。Raltegravir不會誘導 CYP3A4 RNA 表達或 CYP3A4依賴的睪丸激素 6-β-羥化酶活性。[2]在鎂和鈣存在時，Raltegravir細胞擴散性降低。[3]Raltegravir 和相關的HIV-1整合酶 (IN) 鏈轉移抑制劑 (INSTIs) 高效阻斷病毒復制。[4] Raltegravir 作用于急性感染人類淋巴 CD4+ T細胞系MT-4和 CEMx174, 高效抑制SIVmac251復制，EC90處于低納摩爾范圍。[5]
激酶實驗 PFV 整合實驗
為了定量分析鏈轉移，供體DNA底物通過退火 HPLC 級寡核苷酸 5′-GACTCACTATAGGGCACGCGTCAAAATTCCATGACA 和 5′-ATTGTCATG GAATTTTGACGCGTGCCCTATAGTGAGTC而形成。反應(40 μL) 含0.75 μM PFV IN, 0.75 μM 供體 DNA, 4 nM (300 ng) 超螺旋 pGEM9-Zf(?) 靶 DNA, 125 mM NaCl, 5 mM MgSO4, 4 μM ZnCl2, 10 mM DTT, 0.8% (vol/vol) DMSO, 和 25 mM BisTris 丙烷–HCl, pH 7.45。加入指定濃度Raltegravir。加入2 μL PFV IN （在150 mM NaCl, 2 mM DTT, 和 10 mM Tris-HCl, pH 7.4中稀釋）開始反應,在 37oC下反應1小時后，加入25 mM EDTA 和 0.5% (wt/vol) SDS終止反應。反應產(chǎn)物通過與 20 μg 蛋白酶 K 在 37oC下消化30分鐘而脫蛋白，隨后使用乙醇 沉淀,在 在1.5％瓊脂糖凝膠上分離，然后通過用溴化乙錠染色觀察。通過實時定量PCR, 使用 Platinum SYBR Green qPCR SuperMix 和三種引物 : 5′-CTACTTACTCTAGCTTCCCGGCAAC, 5′-TTCGCCAGTTAATAGTTTGCGCAAC, 和 5′-GACTCACTATAGGGCACGCGT定量分析整合產(chǎn)物。PCR 反應 (20 μL) 含0.5 μM 每種引物和1 μL 稀釋的整合反應產(chǎn)物。在95oC下進行5分鐘變性，在CFX96 PCR儀上進行35次循環(huán)，再在95oC下變性10秒，在56oC下退火30秒，在68oC下延伸1分鐘。在INSTI存在時，使用連續(xù)稀釋的WT PFV IN 反應，獲得標準曲線。
細胞實驗 細胞系 人類MT-4 細胞
濃度 0.0001 μM -1 μM
孵育時間 2小時
方法

使用 SIVmac251, HIV-1 (IIIB) 和 HIV-2 (CDC 77618)對人類MT-4細胞進行多重感染2小時。然后在PBS中沖洗細胞3次，在有或無一系列一式三份Raltegravir 濃度 (0.0001 μM -1 μM)時，按5 × 105/mL 懸浮在含新鮮培養(yǎng)基 (在原代細胞中加入 50 單位/mL IL-2 ) 的96孔板中。也制備未治療的感染對照和模擬感染對照，用于比較不同處理法得到的實驗數(shù)據(jù)。通過MTT法(MT-4/MTT實驗 )定量分析致MT-4細胞死亡的病毒。顯微鏡檢測發(fā)現(xiàn)病毒感染的細胞培養(yǎng)物由于缺乏成簇的能力而大量死亡。移液打斷成簇，在 37oC下溫育2小時后, 通過光學顯微鏡l (100 × 放大倍數(shù))觀察新簇形成。通過ELISA收集細胞培養(yǎng)上清液，用于測量HIV-1 p24 和 HIV-2/SIVmac251 p27核心抗原。在CEMx174感染的細胞培養(yǎng)物中，具有病毒包膜糖蛋白誘導形成多核體的傾向,按盲實驗形式計數(shù)多核體，感染5天后，通過光學顯微鏡觀察每孔。
實驗圖片 檢測方法 檢測指標 實驗圖片 PMID
Western blot

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