摘要
2019 年 12 月出现的冠状病毒病 (COVID-19) 是由严重急性呼吸系统综合症相关的冠状病毒 2 (SARS-CoV-2) 引起的。它在全球范围内的迅速传播带来了国际卫生紧急情况和寻求有效预防和治疗的紧急反应。这导致迫切需要说明 SARS-CoV-2 的分子发病机制、分子靶标或受体的鉴定以及抗病毒药物、抗体和疫苗的开发。在这项研究中,我们调查了当前对抗 SARS-CoV-2 感染的研究进展。基于已发表的研究结果,我们首先在分子水平上阐明了 SARS-CoV-2 病毒结构、潜在的病毒宿主细胞入侵、致病机制、主要病毒诱导的免疫反应和新出现的 SARS-CoV-2 变体.然后,我们专注于主要的基于病毒和宿主的潜在靶标,并根据 COVID-19 的药物开发策略对有效抑制分子进行了总结和分类,这些策略可以指导新药的识别和这一问题疾病的治疗。还介绍和讨论了目前抗体和疫苗的研究和开发。我们得出的结论是,主要的病毒进入途径——SARS-CoV-2 刺突蛋白与 ACE2 受体的相互作用在指导 COVID-19 治疗方法的开发中发挥了关键作用。在开发分子疗法时可以考虑四种主要策略,在迫切需要抗病毒药物的如此短的时间内,药物再利用可能是一种简单、快速和低成本的方法。此外,抗体和候选疫苗的快速开发取得了可喜的成果,但安全有效的 COVID-19 疫苗的大规模部署对于解决大流行危机仍然至关重要。随着病毒新变种的出现,必须密切评估这些疫苗和治疗的功效。最后,我们讨论了开发 COVID-19 分子疗法可能面临的挑战,并提出了一些潜在的未来努力。尽管文献有限,我们在这项工作中尝试对当前的 SARS-CoV-2 研究提供一个相对全面的概述,这有助于快速获取 COVID-19 的关键信息,并进一步推动这项重要研究以控制和减少大流行。
关键词: SARS-CoV-2、COVID-19、病毒分子、潜在靶点、分子抑制剂、抗体、疫苗。
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[http://dx.doi.org/10.1093/jtm/taaa008] [PMID: 31943059]
[http://dx.doi.org/10.1038/s41586-020-2179-y] [PMID: 32225175]
[http://dx.doi.org/10.1016/j.antiviral.2020.104786] [PMID: 32251767]
[http://dx.doi.org/10.1056/NEJMoa2001282] [PMID: 32187464]
[http://dx.doi.org/10.1016/j.ejim.2020.10.015] [PMID: 33127218]
[http://dx.doi.org/10.1016/S0140-6736(20)31042-4] [PMID: 32401715]
[http://dx.doi.org/10.12659/MSM.924700] [PMID: 32366816]
[http://dx.doi.org/10.2478/jtim-2020-0003] [PMID: 32435607]
[http://dx.doi.org/10.3390/biomedicines8050109] [PMID: 32375268]
[http://dx.doi.org/10.1016/j.it.2020.03.007] [PMID: 32249063]
[http://dx.doi.org/10.1016/j.dsx.2020.04.020] [PMID: 32335367]
[http://dx.doi.org/10.1016/j.chom.2020.02.001] [PMID: 32035028]
[http://dx.doi.org/10.2174/2666796701999201209144207]
[PMID: 32906143]
[http://dx.doi.org/10.1016/j.lfs.2020.117627] [PMID: 32251634]
[http://dx.doi.org/10.1038/s41421-020-0153-3]
[http://dx.doi.org/10.1038/s41401-020-0485-4] [PMID: 32747721]
[http://dx.doi.org/10.1016/j.cell.2020.02.058] [PMID: 32155444]
[http://dx.doi.org/10.1016/j.antiviral.2020.104742] [PMID: 32057769]
[http://dx.doi.org/10.1016/j.antiviral.2020.104792] [PMID: 32272173]
[http://dx.doi.org/10.1186/s12985-019-1182-0] [PMID: 31133031]
[http://dx.doi.org/10.1371/journal.pone.0237300] [PMID: 32785274]
[http://dx.doi.org/10.1016/j.jsb.2010.11.021] [PMID: 21130884]
[http://dx.doi.org/10.1155/2020/4389089] [PMID: 32596311]
[http://dx.doi.org/10.1007/s11373-005-9035-9] [PMID: 16228284]
[http://dx.doi.org/10.1038/s41594-020-00533-x] [PMID: 33082564]
[http://dx.doi.org/10.1101/2020.07.13.201517]
[http://dx.doi.org/10.1016/j.isci.2020.101258] [PMID: 32592996]
[http://dx.doi.org/10.1016/j.apsb.2020.02.008] [PMID: 32292689]
[http://dx.doi.org/10.1016/j.genrep.2020.100682] [PMID: 32300673]
[http://dx.doi.org/10.1186/s12985-020-01402-1] [PMID: 32854725]
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[http://dx.doi.org/10.1016/j.bbrc.2020.03.044] [PMID: 32199615]
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[http://dx.doi.org/10.1002/jmv.25681] [PMID: 31967327]
[http://dx.doi.org/10.1038/s41594-020-0440-6] [PMID: 32382072]
[http://dx.doi.org/10.1038/s41586-020-2601-5] [PMID: 32726803]
[http://dx.doi.org/10.3390/v12040428] [PMID: 32290077]
[http://dx.doi.org/10.1126/science.abb2762] [PMID: 32132184]
[http://dx.doi.org/10.1128/AAC.00754-20] [PMID: 32312781]
[http://dx.doi.org/10.1128/JVI.00127-20] [PMID: 31996437]
[http://dx.doi.org/10.1126/science.abb2507] [PMID: 32075877]
[http://dx.doi.org/10.1007/s11427-020-1637-5] [PMID: 32009228]
[http://dx.doi.org/10.1016/j.jbc.2021.100847] [PMID: 34058196]
[http://dx.doi.org/10.1016/j.jemermed.2020.10.010] [PMID: 33208227]
[http://dx.doi.org/10.1038/s41392-020-00426-x] [PMID: 33277466]
[http://dx.doi.org/10.1007/s00705-015-2579-8] [PMID: 26321473]
[http://dx.doi.org/10.1016/j.antiviral.2020.104759] [PMID: 32130973]
[http://dx.doi.org/10.1016/j.jacbts.2020.10.003]
[http://dx.doi.org/10.1371/journal.pone.0034747] [PMID: 22523556]
[http://dx.doi.org/10.1016/j.bbadis.2004.05.005] [PMID: 15276642]
[http://dx.doi.org/10.1172/jci.insight.129259] [PMID: 31873073]
[http://dx.doi.org/10.1016/j.cytogfr.2020.06.001] [PMID: 32513566]
[http://dx.doi.org/10.1007/978-981-15-4814-7_5]
[http://dx.doi.org/10.1159/000503030] [PMID: 31610541]
[http://dx.doi.org/10.1016/j.jpha.2020.03.001] [PMID: 32282863]
[http://dx.doi.org/10.1038/s12276-021-00602-1] [PMID: 33953325]
[http://dx.doi.org/10.1016/j.lfs.2020.117900] [PMID: 32502542]
[http://dx.doi.org/10.1126/science.abb4489] [PMID: 32321856]
[http://dx.doi.org/10.1021/acs.jcim.0c00491] [PMID: 32530282]
[http://dx.doi.org/10.26633/RPSP.2020.40] [PMID: 32256547]
[http://dx.doi.org/10.3390/ijms21083003] [PMID: 32344526]
[http://dx.doi.org/10.1038/s41586-020-2180-5] [PMID: 32225176]
[http://dx.doi.org/10.1074/jbc.M111.325803] [PMID: 22291007]
[PMID: 17974127]
[http://dx.doi.org/10.1056/NEJMoa2008975] [PMID: 32356628]
[http://dx.doi.org/10.1136/heartjnl-2020-317393] [PMID: 32737124]
[http://dx.doi.org/10.1038/s41591-021-01397-4] [PMID: 34045737]
[http://dx.doi.org/10.1038/s41586-021-03398-2] [PMID: 33684923]
[http://dx.doi.org/10.15585/mmwr.mm7003e2] [PMID: 33476315]
[http://dx.doi.org/10.1371/journal.ppat.1009233] [PMID: 33476327]
[http://dx.doi.org/10.1038/s41586-021-03426-1] [PMID: 33723411]
[http://dx.doi.org/10.1038/s41591-021-01318-5] [PMID: 33772244]
[http://dx.doi.org/10.1002/jcp.30367] [PMID: 33755190]
[http://dx.doi.org/10.15585/mmwr.mm7008e2] [PMID: 33630820]
[http://dx.doi.org/10.15585/mmwr.mm7017a5] [PMID: 33914724]
[http://dx.doi.org/10.7554/eLife.61312] [PMID: 33112236]
[http://dx.doi.org/10.1056/NEJMc2104974] [PMID: 33951357]
[http://dx.doi.org/10.1038/s41591-021-01378-7] [PMID: 34035535]
[http://dx.doi.org/10.1016/j.jinf.2021.03.013] [PMID: 33766552]
[http://dx.doi.org/10.15585/mmwr.mm7010e1] [PMID: 33705367]
[http://dx.doi.org/10.1038/s41577-021-00556-5] [PMID: 33927376]
[http://dx.doi.org/10.3390/ijms21093076] [PMID: 32349271]
[PMID: 33272178]
[http://dx.doi.org/10.2174/2666796701999200831105801]
[http://dx.doi.org/10.21203/rs.2.24684/v1]
[http://dx.doi.org/10.1590/0074-02760200254] [PMID: 33027420]
[http://dx.doi.org/10.1038/d41573-020-00016-0] [PMID: 32127666]
[http://dx.doi.org/10.1016/j.mehy.2020.110011] [PMID: 32593831]
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105944] [PMID: 32179150]
[http://dx.doi.org/10.1038/s41422-020-0305-x] [PMID: 32231345]
[http://dx.doi.org/10.3389/fbioe.2020.01020] [PMID: 32974328]
[http://dx.doi.org/10.1080/07391102.2020.1792992] [PMID: 32657643]
[http://dx.doi.org/10.1016/j.lfs.2020.117652] [PMID: 32278693]
[http://dx.doi.org/10.1128/JVI.01648-20] [PMID: 33055254]
[http://dx.doi.org/10.1080/07391102.2020.1779133] [PMID: 32573355]
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[http://dx.doi.org/10.1016/j.antiviral.2020.104878] [PMID: 32679055]
[http://dx.doi.org/10.1038/s41467-020-18463-z] [PMID: 32943628]
[http://dx.doi.org/10.1021/acs.jmedchem.9b01828] [PMID: 32045235]
[http://dx.doi.org/10.1126/science.abb3405] [PMID: 32198291]
[http://dx.doi.org/10.1101/2020.01.27.921627]
[http://dx.doi.org/10.1016/j.jgg.2020.02.001] [PMID: 32173287]
[http://dx.doi.org/10.1021/acs.jcim.0c00179] [PMID: 32315171]
[http://dx.doi.org/10.1007/s13659-020-00253-1] [PMID: 32557405]
[PMID: 32608329]
[http://dx.doi.org/10.1038/s41467-021-20900-6] [PMID: 33510133]
[http://dx.doi.org/10.1073/pnas.2012201118] [PMID: 33597253]
[http://dx.doi.org/10.3390/ph13100277] [PMID: 32998368]
[http://dx.doi.org/10.1007/s11095-020-02851-7] [PMID: 32778962]
[http://dx.doi.org/10.1021/acsinfecdis.0c00052] [PMID: 32125140]
[http://dx.doi.org/10.7326/M20-3689] [PMID: 32589451]
[http://dx.doi.org/10.1073/pnas.2005615117] [PMID: 32350134]
[http://dx.doi.org/10.1038/d41587-020-00003-1] [PMID: 32205870]
[http://dx.doi.org/10.1186/s43141-020-00055-5] [PMID: 32725286]
[http://dx.doi.org/10.1126/sciadv.aav4580] [PMID: 30989115]
[http://dx.doi.org/10.1128/JVI.02322-09] [PMID: 20032190]
[http://dx.doi.org/10.1002/jmv.26264] [PMID: 32633831]
[http://dx.doi.org/10.1038/nature17180] [PMID: 26934220]
[http://dx.doi.org/10.3390/v11040326] [PMID: 30987343]
[http://dx.doi.org/10.1126/science.abc1560] [PMID: 32358203]
[PMID: 32649078]
[http://dx.doi.org/10.1016/j.antiviral.2018.05.013] [PMID: 29864447]
[http://dx.doi.org/10.1002/cpt.1844] [PMID: 32246834]
[PMID: 33765239]
[http://dx.doi.org/10.1002/cpt.2251] [PMID: 33882157]
[http://dx.doi.org/10.1007/s00705-020-04706-3] [PMID: 32594322]
[http://dx.doi.org/10.1016/j.ejphar.2010.04.033] [PMID: 20447389]
[http://dx.doi.org/10.1016/j.jcv.2007.10.011] [PMID: 18036887]
[http://dx.doi.org/10.3389/fimmu.2020.02159] [PMID: 32983179]
[http://dx.doi.org/10.1016/S2665-9913(20)30120-X] [PMID: 32835246]
[http://dx.doi.org/10.1038/s41421-020-0156-0] [PMID: 33731711]
[http://dx.doi.org/10.1016/j.lfs.2020.117775] [PMID: 32418894]
[http://dx.doi.org/10.1016/j.tmaid.2020.101716] [PMID: 32360423]
[http://dx.doi.org/10.1016/j.ejim.2020.08.019] [PMID: 32859477]
[http://dx.doi.org/10.1161/CIRCEP.120.008662] [PMID: 32347743]
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949] [PMID: 32205204]
[http://dx.doi.org/10.4172/1948-5964.1000173]
[http://dx.doi.org/10.1099/jgv.0.001047] [PMID: 29557770]
[http://dx.doi.org/10.1128/JVI.01218-20] [PMID: 32817221]
[http://dx.doi.org/10.1016/S0140-6736(20)30304-4] [PMID: 32032529]
[http://dx.doi.org/10.1128/AAC.00819-20] [PMID: 32366720]
[http://dx.doi.org/10.1016/j.virusres.2019.02.011] [PMID: 30794895]
[http://dx.doi.org/10.1126/science.aad5224] [PMID: 26917593]
[http://dx.doi.org/10.1128/JVI.02002-17] [PMID: 29514901]
[http://dx.doi.org/10.1016/j.cell.2020.05.025] [PMID: 32425270]
[http://dx.doi.org/10.1038/s41467-020-18174-5] [PMID: 32887876]
[http://dx.doi.org/10.1038/s41586-020-2380-z] [PMID: 32454513]
[http://dx.doi.org/10.1038/s41586-020-2349-y] [PMID: 32422645]
[http://dx.doi.org/10.1101/2020.05.11.088674]
[http://dx.doi.org/10.1080/22221751.2020.1729069] [PMID: 32065055]
[http://dx.doi.org/10.1016/j.cell.2020.09.007] [PMID: 32941803]
[http://dx.doi.org/10.1016/j.celrep.2020.107918] [PMID: 32668215]
[http://dx.doi.org/10.1126/science.abc2241] [PMID: 32404477]
[http://dx.doi.org/10.1038/s41467-020-16256-y] [PMID: 32366817]
[http://dx.doi.org/10.1016/j.cell.2020.09.049] [PMID: 33058755]
[http://dx.doi.org/10.1126/science.abb7269] [PMID: 32245784]
[http://dx.doi.org/10.1038/s41586-020-2381-y] [PMID: 32454512]
[http://dx.doi.org/10.1038/s41594-020-0469-6] [PMID: 32661423]
[http://dx.doi.org/10.1016/j.cell.2020.09.037] [PMID: 32991844]
[http://dx.doi.org/10.1016/j.cell.2020.06.025] [PMID: 32645326]
[http://dx.doi.org/10.1038/s41586-020-2852-1] [PMID: 33045718]
[http://dx.doi.org/10.1126/science.abd2321] [PMID: 32661058]
[http://dx.doi.org/10.1056/NEJMoa2035002]
[http://dx.doi.org/10.1016/j.lfs.2020.117956] [PMID: 32535078]
[http://dx.doi.org/10.1126/science.abc1932] [PMID: 32376603]
[http://dx.doi.org/10.1016/j.heliyon.2020.e05007] [PMID: 32984620]
[http://dx.doi.org/10.1128/CMR.8.3.406]
[http://dx.doi.org/10.1038/nrd.2017.243] [PMID: 29326426]
[http://dx.doi.org/10.3390/vaccines9020147] [PMID: 33673048]
[PMID: 33306989]
[http://dx.doi.org/10.1016/S0140-6736(20)31866-3] [PMID: 32896291]
[http://dx.doi.org/10.1056/NEJMoa2034577] [PMID: 33301246]
[http://dx.doi.org/10.1136/bmj.m4471]
[http://dx.doi.org/10.1056/NEJMoa2022483] [PMID: 32663912]
[http://dx.doi.org/10.1038/s41587-020-0732-8] [PMID: 33087898]