A decade after SARS: strategies for controlling emerging coronaviruses.
A decade after SARS: strategies for controlling emerging coronaviruses.
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DOI：
10.1038/nrmicro3143
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发表时间：
2013-12
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影响因子：
--
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过去十年中出现了两种高致病性人类冠状病毒，即严重急性呼吸综合征冠状病毒（SARS-CoV）和中东呼吸综合征冠状病毒（MERS-CoV）。由于缺乏针对这两种病毒的任何临床批准的抗病毒治疗或疫苗，这凸显了设计有效治疗和预防措施的重要性。蝙蝠被认为是 SARS-CoV 和 MERS-CoV 以及相关病毒和其他人类冠状病毒 (HCoV)（例如 HCoV-229E 和 HCoV-NL63）的宿主。蝙蝠物种在全球大部分地区的分散可能增强了它们作为病原体储存库的潜力，其中一些病原体毒性极强，对其他动物和人类可能致命。尽管小鼠模型的特征最为彻底，但存在多种 SARS-CoV 感染动物模型。小鼠适应的 SARS-CoV 能够在幼年和老年动物中引起代表人类感染的病理学。尚未报道中东呼吸综合征冠状病毒感染的小动物模型，尽管对刺突蛋白中的受体结合序列或对宿主特异性重要的其他序列进行进一步持续选择的可能性可能会导致这一限制。在接种的猕猴中观察到轻微的疾病表型，包括局部或广泛的肺炎。人们已经尝试了多种针对冠状病毒的疫苗策略，主要（但不限于）针对刺突糖蛋白。成功的减毒活疫苗利用反向遗传策略来删除包膜蛋白或灭活非结构蛋白 14 (nsp14) 的核酸外切酶活性。 MERS-CoV 与 2003 年的 SARS-CoV 类似，有可能对人类产生深远的影响；然而，迄今为止其外显率较低，表明该病毒可能最终无法在人类中形成一席之地，或者它可能仍在适应人类宿主，并且其最严重的影响尚未到来。冠状病毒的系统发育显示出令人难以置信的抗原变异多样性，这导致对不同毒株感染的交叉保护有限，即使在系统发育亚群内也是如此。因此，将新型冠状病毒引入人类和动物种群的风险仍然很高。本文的在线版本 (doi:10.1038/nrmicro3143) 包含补充材料，可供授权用户使用。严重急性呼吸综合征（SARS）冠状病毒以及最近的中东呼吸综合征（MERS）冠状病毒的出现凸显了该病毒家族的致病和流行潜力。在此，格雷厄姆、唐纳森和巴里克回顾了冠状病毒的关键生物学特性，以及如何用潜在的治疗方法来针对它们。本文的在线版本 (doi:10.1038/nrmicro3143) 包含补充材料，可供授权用户使用。二十一世纪在人类中出现了两种新型冠状病毒：严重急性呼吸综合征冠状病毒（SARS-CoV）和中东呼吸综合征冠状病毒（MERS-CoV），这两种病毒都会引起急性呼吸窘迫综合征（ARDS）并与高死亡率相关。目前还没有临床批准的疫苗或抗病毒药物可用于治疗这两种感染；因此，开发可轻松应用于新出现菌株的有效治疗和预防策略是研究重点。在这篇综述中，我们描述了过去 10 年新型人类冠状病毒的出现和鉴定，讨论了它们的关键生物学特征，包括趋向性和受体使用，并总结了开发广泛有效的疫苗的方法。本文的在线版本 (doi:10.1038/nrmicro3143) 包含补充材料，可供授权用户使用。
Two highly pathogenic human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), have emerged in the past decade. The lack of any clinically approved antiviral treatments or vaccines for either virus emphasizes the importance of the design of effective therapeutics and preventives. Bats have been implicated as reservoirs of both SARS-CoV and MERS-CoV as well as related viruses and other human coronaviruses (HCoVs), such as HCoV-229E and HCoV-NL63. The dispersion of bat species over much of the globe probably enhances their potential to act as reservoirs for pathogens, some of which are extremely virulent and potentially lethal to other animals and humans. Multiple animal models for SARS-CoV infection exist, although mouse models have been the most thoroughly characterized. Mouse-adapted SARS-CoV is capable of causing pathology that is representative of human infections in both young and aged animals. Small animal models for MERS-CoV infection have not yet been reported, although the possibility of further ongoing selection in the receptor-binding sequence in the spike protein or other sequences that are important for host specificity might contribute to this limitation. A mild disease phenotype that can include either localized or widespread pneumonia is observed in inoculated macaques. Multiple vaccine strategies have been attempted with coronaviruses, mostly (but not exclusively) targeting the spike glycoprotein. Successful live-attenuated vaccines have utilized reverse genetic strategies to delete the envelope protein or inactivate the exonuclease activity of non-structural protein 14 (nsp14) . MERS-CoV, similarly to SARS-CoV in 2003, has the potential to have a profound impact on the human population; however, its low penetrance thus far suggests that the virus might either ultimately fail to develop a niche in humans or it might still be adapting to human hosts and that the worst of its effects are yet to come. Coronavirus phylogeny shows an incredible diversity in antigenic variants, which leads to limited cross-protection against infection with different strains, even within a phylogenetic subcluster. Consequently, the risk of introducing novel coronaviruses into naive human and animal populations remains high. The online version of this article (doi:10.1038/nrmicro3143) contains supplementary material, which is available to authorized users. The emergence of severe acute respiratory syndrome (SARS) coronavirus and, more recently, Middle East respiratory syndrome (MERS) coronavirus has highlighted the pathogenic and epidemic potential of this virus family. Here, Graham, Donaldson and Baric review key biological properties of coronaviruses and how to target them with potential therapeutics. The online version of this article (doi:10.1038/nrmicro3143) contains supplementary material, which is available to authorized users. Two novel coronaviruses have emerged in humans in the twenty-first century: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), both of which cause acute respiratory distress syndrome (ARDS) and are associated with high mortality rates. There are no clinically approved vaccines or antiviral drugs available for either of these infections; thus, the development of effective therapeutic and preventive strategies that can be readily applied to new emergent strains is a research priority. In this Review, we describe the emergence and identification of novel human coronaviruses over the past 10 years, discuss their key biological features, including tropism and receptor use, and summarize approaches for developing broadly effective vaccines. The online version of this article (doi:10.1038/nrmicro3143) contains supplementary material, which is available to authorized users.
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DOI：
10.1016/j.jinf.2012.10.002
发表时间：
2012-12
期刊：
The Journal of infection
影响因子：
--
作者：
Chan JF;Li KS;To KK;Cheng VC;Chen H;Yuen KY
通讯作者：
Yuen KY
影响因子：
11.8
作者：
Carrington, Christine V. F.;Foster, Jerome E.;Zhu, Hua Chen;Zhang, Jin Xia;Smith, Gavin J. D.;Thompson, Nadin;Auguste, Albert J.;Ramkissoon, Vernie;Adesiyun, Abiodun A.;Guan, Yi
通讯作者：
Guan, Yi
影响因子：
3.7
作者：
Bisht H;Roberts A;Vogel L;Subbarao K;Moss B
通讯作者：
Moss B
DOI：
10.1056/nejmoa1306742
发表时间：
2013-08-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
Assiri A;McGeer A;Perl TM;Price CS;Al Rabeeah AA;Cummings DA;Alabdullatif ZN;Assad M;Almulhim A;Makhdoom H;Madani H;Alhakeem R;Al-Tawfiq JA;Cotten M;Watson SJ;Kellam P;Zumla AI;Memish ZA;KSA MERS-CoV Investigation Team
通讯作者：
KSA MERS-CoV Investigation Team
影响因子：
6.4
作者：
Almazán F;DeDiego ML;Sola I;Zuñiga S;Nieto-Torres JL;Marquez-Jurado S;Andrés G;Enjuanes L
通讯作者：
Enjuanes L