摘要
背景:病毒感染继续严重增加发病率和死亡率。黄病毒属有50个不同的种类,包括登革热病毒、寨卡病毒和西尼罗河病毒,它们可以感染全球40%的人,这些人居住在至少100个不同的国家。登革热是最古老、最危险的人类传染病之一,最早记录在金代的《中国医学百科全书》中。它被称为“水毒”,与飞行昆虫,即埃及伊蚊和白纹伊蚊有关。登革热病毒引起一些医学表达,如登革出血热、急性发热性疾病和登革休克综合征。 目的:根据世界卫生组织2012年的报告,全世界有25亿人有感染登革热的危险。根据最近的一项研究,每年3.9亿登革热感染者中有9600万人表现出某种临床或亚临床严重程度。目前还没有抗病毒药物或疫苗来治疗这种严重的感染。它可以通过充分休息、多喝水和使用止痛药来控制。赛诺菲开发的第一种登革热疫苗名为Dengvaxia,此前已于2019年获得美国FDA的批准。DENV1-4的所有四种血清型均显示在疫苗接种者中再次感染。然而,由于其副作用,邓卡夏的使用受到限制。 结论:对DENV有拮抗作用的化合物有含氮杂环类(咪唑类、吡啶类、三唑类、喹唑类、喹啉类、吲哚类)、含氧杂环类(香豆素类),部分为S、N杂环类(噻唑类、苯并噻嗪类、噻唑烷二酮类)和N、O杂环类(恶二唑类)混合化合物。有报道称,计算设计的化合物可以阻碍特定结构蛋白和非结构蛋白的分子功能,作为潜在的治疗靶点。本文综述了目前登革热蛋白酶抑制剂的研究进展。
关键词: 登革蛋白酶,NS2B, NS3,登革结构蛋白,登革非结构蛋白,多蛋白,病毒感染,黄病毒。
[http://dx.doi.org/10.1016/S0140-6736(14)60629-2] [PMID: 24725560]
[http://dx.doi.org/10.1371/journal.pntd.0000247] [PMID: 18575597]
[http://dx.doi.org/10.1016/S0188-4409(02)00378-8] [PMID: 12234522]
[http://dx.doi.org/10.1039/c4md00011k]
[PMID: 15497006]
[http://dx.doi.org/10.1016/0738-081X(89)90034-5] [PMID: 2647259]
[http://dx.doi.org/10.1136/bmj.324.7353.1563] [PMID: 12089096]
[http://dx.doi.org/10.1038/nrmicro2460] [PMID: 21079655]
[http://dx.doi.org/10.1016/j.ejmech.2021.113527] [PMID: 34020338]
[http://dx.doi.org/10.1007/s00018-010-0357-z] [PMID: 20372965]
[http://dx.doi.org/10.1016/j.antiviral.2012.09.007] [PMID: 22995600]
[http://dx.doi.org/10.1371/journal.pntd.0002311] [PMID: 23875046]
[http://dx.doi.org/10.4269/ajtmh.2011.10-0521] [PMID: 21363989]
[http://dx.doi.org/10.4269/ajtmh.2006.75.1113] [PMID: 17172378]
[http://dx.doi.org/10.1016/S0065-3527(03)60011-4] [PMID: 14689700]
[http://dx.doi.org/10.1016/j.vaccine.2015.09.103]
[PMID: 27476189]
[http://dx.doi.org/10.1021/cr950025u] [PMID: 11848867]
[http://dx.doi.org/10.2174/138161207780162962] [PMID: 17311556]
[http://dx.doi.org/10.1146/annurev.biophys.28.1.181] [PMID: 10410800]
[http://dx.doi.org/10.1016/S0895-7061(99)00236-8] [PMID: 10826406]
[http://dx.doi.org/10.4049/jimmunol.1200901] [PMID: 23543761]
[http://dx.doi.org/10.1016/S0166-6851(01)00438-8] [PMID: 11849701]
[http://dx.doi.org/10.1146/annurev.mi.44.100190.003245] [PMID: 2174669]
[http://dx.doi.org/10.1128/JVI.01257-06] [PMID: 16928749]
[http://dx.doi.org/10.1128/jvi.71.11.8475-8481.1997] [PMID: 9343204]
[http://dx.doi.org/10.1007/s00253-018-8822-y] [PMID: 29470620]
[http://dx.doi.org/10.1038/nature02165] [PMID: 14737159]
[http://dx.doi.org/10.1146/annurev-virology-110615-042334] [PMID: 27501261]
[http://dx.doi.org/10.1016/j.antiviral.2018.04.019] [PMID: 29709563]
[http://dx.doi.org/10.1074/jbc.M114.610428] [PMID: 25326389]
[http://dx.doi.org/10.1038/sj.embor.embor866] [PMID: 12783086]
[http://dx.doi.org/10.1016/j.antiviral.2009.12.011] [PMID: 20060421]
[http://dx.doi.org/10.1038/nrmicro1067] [PMID: 15608696]
[http://dx.doi.org/10.1128/AAC.01148-08] [PMID: 19223625]
[http://dx.doi.org/10.1016/j.antiviral.2009.09.011] [PMID: 19800368]
[http://dx.doi.org/10.1021/cb800176t] [PMID: 19053243]
[http://dx.doi.org/10.1016/j.antiviral.2009.09.007] [PMID: 19781577]
[http://dx.doi.org/10.1371/journal.ppat.1007553] [PMID: 30703168]
[http://dx.doi.org/10.1371/journal.pntd.0000721] [PMID: 20582308]
[http://dx.doi.org/10.1186/1743-422X-2-1]
[http://dx.doi.org/10.1073/pnas.0832193100] [PMID: 12759475]
[http://dx.doi.org/10.1016/j.antiviral.2013.09.013] [PMID: 24076358]
[http://dx.doi.org/10.7150/ijms.5037] [PMID: 23630436]
[http://dx.doi.org/10.1016/j.bmcl.2015.02.059] [PMID: 25791449]
[http://dx.doi.org/10.1016/j.antiviral.2017.11.005] [PMID: 29129706]
[http://dx.doi.org/10.1371/journal.ppat.1000632] [PMID: 19851456]
[http://dx.doi.org/10.1128/AAC.01429-12] [PMID: 23070172]
[http://dx.doi.org/10.1016/j.antiviral.2015.01.002] [PMID: 25614455]
[http://dx.doi.org/10.1016/j.antiviral.2017.03.026] [PMID: 28389141]
[http://dx.doi.org/10.1016/j.virol.2016.06.008]
[http://dx.doi.org/10.1128/JVI.73.6.4611-4621.1999] [PMID: 10233920]
[http://dx.doi.org/10.1016/j.vaccine.2005.11.002]
[http://dx.doi.org/10.1128/jvi.65.4.1823-1828.1991] [PMID: 1705990]
[http://dx.doi.org/10.1016/j.vaccine.2015.09.102]
[http://dx.doi.org/10.1186/1471-2180-14-140]
[http://dx.doi.org/10.1016/0959-440X(95)80051-4] [PMID: 8574695]
[http://dx.doi.org/10.1096/fasebj.5.15.1743438] [PMID: 1743438]
[http://dx.doi.org/10.1021/bi00285a038]
[http://dx.doi.org/10.1038/nm0598-610] [PMID: 9585237]
[http://dx.doi.org/10.1128/JVI.74.1.564-572.2000] [PMID: 10590151]
[http://dx.doi.org/10.1086/511310] [PMID: 17262707]
[http://dx.doi.org/10.1016/S0021-9258(18)98715-6] [PMID: 1650361]
[http://dx.doi.org/10.1042/bj20020466] [PMID: 11982484]
[http://dx.doi.org/10.1016/j.antiviral.2011.10.002] [PMID: 22020302]
[http://dx.doi.org/10.1186/s12985-014-0235-7]
[http://dx.doi.org/10.1021/jp504911r] [PMID: 25119664]
[http://dx.doi.org/10.1016/j.bbamem.2015.06.010]
[http://dx.doi.org/10.1074/jbc.M112.442723] [PMID: 23511634]
[http://dx.doi.org/10.1371/journal.pone.0210869] [PMID: 30677071]
[http://dx.doi.org/10.1128/AAC.00855-10] [PMID: 20937790]
[http://dx.doi.org/10.1016/j.bioorg.2015.07.005] [PMID: 26247308]
[http://dx.doi.org/10.1038/aps.2015.56] [PMID: 26279156]
[http://dx.doi.org/10.1016/j.apsb.2017.04.009] [PMID: 28752033]
[http://dx.doi.org/10.1016/j.ejmech.2016.09.063] [PMID: 27721158]
[http://dx.doi.org/10.1016/j.bioorg.2020.103567] [PMID: 32062063]
[http://dx.doi.org/10.1016/j.bmc.2011.05.015] [PMID: 21641807]
[http://dx.doi.org/10.1016/j.bmc.2012.10.058] [PMID: 23211969]
[http://dx.doi.org/10.1016/j.antiviral.2012.10.009] [PMID: 23127365]
[http://dx.doi.org/10.1021/acs.jmedchem.5b01441] [PMID: 26562070]
[http://dx.doi.org/10.1021/jm400828u] [PMID: 24083834]
[http://dx.doi.org/10.1016/j.bmc.2014.09.057] [PMID: 25438757]
[http://dx.doi.org/10.1016/j.bmc.2009.12.026] [PMID: 20042339]
[http://dx.doi.org/10.1016/j.bbrc.2013.03.139] [PMID: 23587903]
[http://dx.doi.org/10.1021/acs.jmedchem.5b00612] [PMID: 26367391]
[http://dx.doi.org/10.1006/viro.1993.1198]
[http://dx.doi.org/10.1128/jvi.65.5.2467-2475.1991] [PMID: 2016768]
[http://dx.doi.org/10.1128/jvi.67.4.2034-2042.1993] [PMID: 8383225]
[http://dx.doi.org/10.1128/JVI.73.4.3108-3116.1999] [PMID: 10074162]
[http://dx.doi.org/10.1074/jbc.275.14.9963] [PMID: 10744671]
[http://dx.doi.org/10.1074/jbc.M107360200] [PMID: 11581268]
[http://dx.doi.org/10.1074/jbc.M500588200] [PMID: 15932883]
[http://dx.doi.org/10.1074/jbc.274.9.5573] [PMID: 10026173]
[http://dx.doi.org/10.2174/138161206776361110] [PMID: 16611117]
[http://dx.doi.org/10.1016/j.antiviral.2009.07.006] [PMID: 19616029]
[http://dx.doi.org/10.1590/S1415-47572010000200002] [PMID: 21637471]
[http://dx.doi.org/10.1016/0042-6822(89)90639-9]
[http://dx.doi.org/10.1038/nsmb1073] [PMID: 16532006]
[http://dx.doi.org/10.1128/AAC.01508-07] [PMID: 18606844]
[http://dx.doi.org/10.1016/j.antiviral.2015.04.010] [PMID: 25912817]
[http://dx.doi.org/10.1016/j.antiviral.2015.03.007] [PMID: 25796970]
[http://dx.doi.org/10.3390/md14080151] [PMID: 27517937]
[http://dx.doi.org/10.1128/JVI.00423-15] [PMID: 25878113]
[http://dx.doi.org/10.1128/AAC.03543-14] [PMID: 25487800]
[http://dx.doi.org/10.1128/AAC.01281-13] [PMID: 24145533]
[http://dx.doi.org/10.1016/j.antiviral.2016.08.014] [PMID: 27539384]
[PMID: 33593007]
[http://dx.doi.org/10.1016/j.actatropica.2018.08.022] [PMID: 30145258]
[http://dx.doi.org/10.1080/14756366.2017.1355791] [PMID: 28776445]
[http://dx.doi.org/10.1074/jbc.M609919200] [PMID: 17276984]
[http://dx.doi.org/10.1016/j.bbamem.2017.10.016] [PMID: 29055659]
[http://dx.doi.org/10.3390/v7072812]
[http://dx.doi.org/10.1128/JVI.01900-12] [PMID: 23325687]
[http://dx.doi.org/10.1128/JVI.00546-15] [PMID: 25833044]
[http://dx.doi.org/10.1128/JVI.03453-14] [PMID: 25568208]
[http://dx.doi.org/10.1128/jvi.67.4.2327-2335.1993] [PMID: 8445732]
[http://dx.doi.org/10.1016/j.bcp.2018.04.008] [PMID: 29674002]
[http://dx.doi.org/10.1128/JVI.05864-11] [PMID: 21880777]
[http://dx.doi.org/10.1128/JVI.79.16.10268-10277.2005] [PMID: 16051820]
[http://dx.doi.org/10.1016/j.virol.2007.12.018]
[http://dx.doi.org/10.1016/j.antiviral.2018.05.003] [PMID: 29758236]
[http://dx.doi.org/10.1074/jbc.M512697200] [PMID: 16436383]
[http://dx.doi.org/10.1002/ange.201606609]
[http://dx.doi.org/10.1099/vir.0.81844-0] [PMID: 16894199]
[http://dx.doi.org/10.1128/JVI.02782-13] [PMID: 24390334]
[http://dx.doi.org/10.1002/rmv.1835] [PMID: 25828437]
[http://dx.doi.org/10.1016/j.virol.2008.11.003]
[http://dx.doi.org/10.1002/cmdc.201300505] [PMID: 24574246]
[http://dx.doi.org/10.1128/JVI.05468-11] [PMID: 21865382]
[http://dx.doi.org/10.1016/j.antiviral.2013.05.011] [PMID: 23735301]
[http://dx.doi.org/10.1128/JVI.00855-15] [PMID: 26018165]
[http://dx.doi.org/10.1128/AAC.02462-15] [PMID: 26856827]
[http://dx.doi.org/10.1128/JVI.00665-11] [PMID: 21632767]
[http://dx.doi.org/10.1021/ml500521r] [PMID: 25878766]
[http://dx.doi.org/10.1016/j.bmcl.2017.02.005] [PMID: 28216045]
[http://dx.doi.org/10.1016/j.antiviral.2017.10.011] [PMID: 29037976]
[http://dx.doi.org/10.1016/S0065-3527(09)74002-3] [PMID: 19698895]
[http://dx.doi.org/10.1016/j.antiviral.2008.06.007] [PMID: 18611413]
[http://dx.doi.org/10.1074/jbc.M113.508606] [PMID: 24025331]
[http://dx.doi.org/10.1128/JVI.00814-06] [PMID: 16912287]
[http://dx.doi.org/10.1128/JVI.02704-06] [PMID: 17267492]
[http://dx.doi.org/10.3390/v9040091]
[http://dx.doi.org/10.1016/j.virol.2010.06.039]
[http://dx.doi.org/10.1038/ni.1979] [PMID: 21217758]
[http://dx.doi.org/10.1371/journal.ppat.1003521] [PMID: 23935499]
[http://dx.doi.org/10.1099/vir.0.82757-0] [PMID: 17622627]
[http://dx.doi.org/10.1016/j.jmb.2008.10.028] [PMID: 18976670]
[http://dx.doi.org/10.1093/emboj/21.11.2757] [PMID: 12032088]
[http://dx.doi.org/10.1016/j.jmb.2008.11.058] [PMID: 19101564]
[http://dx.doi.org/10.1107/S0907444909017260] [PMID: 19622863]
[http://dx.doi.org/10.1110/ps.072758107] [PMID: 17473012]
[http://dx.doi.org/10.1074/jbc.M110.179184] [PMID: 21147775]
[http://dx.doi.org/10.1371/journal.pone.0012836] [PMID: 20862256]
[http://dx.doi.org/10.1371/journal.pone.0025795] [PMID: 22022449]
[http://dx.doi.org/10.1093/nar/gku666] [PMID: 25209234]
[http://dx.doi.org/10.1016/j.antiviral.2008.08.005] [PMID: 18809436]
[http://dx.doi.org/10.1099/vir.0.015511-0] [PMID: 19776234]
[http://dx.doi.org/10.1016/j.virol.2010.03.011] [PMID: 19776122]
[http://dx.doi.org/10.1016/j.antiviral.2013.06.001] [PMID: 23769894]
[http://dx.doi.org/10.1074/jbc.M110.129197] [PMID: 20685660]
[http://dx.doi.org/10.1016/j.antiviral.2014.09.003] [PMID: 25241250]
[http://dx.doi.org/10.1002/pro.2594] [PMID: 25352331]
[http://dx.doi.org/10.1016/j.ejmech.2017.10.064] [PMID: 29137867]
[http://dx.doi.org/10.1002/cmdc.201800178] [PMID: 29740962]
[http://dx.doi.org/10.1016/j.ejmech.2015.12.046] [PMID: 26774922]
[http://dx.doi.org/10.1128/AAC.02203-15] [PMID: 26574011]
[http://dx.doi.org/10.1021/acs.jmedchem.6b00143] [PMID: 26984786]
[http://dx.doi.org/10.1371/journal.ppat.1005737] [PMID: 27500641]
[http://dx.doi.org/10.1038/s41598-017-04449-3] [PMID: 28127051]
[http://dx.doi.org/10.1016/j.bmcl.2018.04.069] [PMID: 29801997]
[http://dx.doi.org/10.1016/j.antiviral.2016.09.007] [PMID: 27649989]
[http://dx.doi.org/10.1016/j.ejphar.2017.12.029]
[http://dx.doi.org/10.1021/acs.jmedchem.5b00327] [PMID: 25909386]
[http://dx.doi.org/10.1016/j.ejmech.2016.10.007] [PMID: 27750202]
[http://dx.doi.org/10.1371/journal.pone.0130062] [PMID: 26098995]
[http://dx.doi.org/10.1080/13543784.2016.1201063] [PMID: 27322111]