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中东呼吸综合征病毒（MERS-CoV）蛋白的分子特征、功能及其致病性 Review

李艳华, 胡晨雨, 吴南屏, 姚航平, 李兰娟

《工程（英文）》 2019年 第5卷 第5期   页码 940-947 doi: 10.1016/j.eng.2018.11.035

摘要：

中东呼吸综合征（MERS）是由一种新型冠状病毒——中东呼吸综合征冠状病毒（MERS-CoV）引起的病毒性呼吸道疾病，病死率高。然而，MERS-CoV感染人类的机制仍不清楚。尽管目前正在研究病毒的快速诊断技术并加强公共卫生的管理，但感染MERS-CoV的病例仍在不断出现。因此，需要实施各种有效措施防止疫情恶化。进一步研究病毒的流行病学特征和发病机制，以及开发有效的抗MERS-CoV感染的治疗和预防性药物是十分必要的。为此，我们需要明确MERS-CoV各种蛋白的详细信息。在文中论述了MERS-CoV的主要结构蛋白和非结构蛋白，并总结了抑制MERS-CoV感染的各种潜在的策略。计算生物学和病毒学的结合可以促进抗MERS-CoV的有效肽治疗剂的设计和开发。

关键词： MERS-CoV     刺突蛋白     结构蛋白     辅助蛋白     非结构蛋白    

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Human monoclonal antibodies as candidate therapeutics against emerging viruses

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《医学前沿（英文）》 2017年 第11卷 第4期   页码 462-470 doi: 10.1007/s11684-017-0596-6

摘要：

The emergence of new pathogens, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus, poses serious challenges to global public health and highlights the urgent need for novel antiviral approaches. Monoclonal antibodies (mAbs) have been successfully used to treat various diseases, particularly cancer and immunological disorders. Antigen-specific mAbs have been isolated using several different approaches, including hybridoma, transgenic mice, phage display, yeast display, and single B-cell isolation. Consequently, an increasing number of mAbs, which exhibit high potency against emerging viruses in vitro and in animal models of infection, have been developed. In this paper, we summarize historical trends and recent developments in mAb discovery, compare the advantages and disadvantages of various approaches to mAb production, and discuss the potential use of such strategies for the development of antivirals against emerging diseases. We also review the application of recently developed human mAbs against SARS-CoV, MERS-CoV, and Ebola virus and discuss prospects for the development of mAbs as therapeutic agents against emerging viral diseases.

关键词： human monoclonal antibodies     emerging infectious diseases     SARS-CoV     MERS-CoV     Ebola virus    

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Middle East respiratory syndrome coronavirus in pediatrics: a report of seven cases from Saudi Arabia

Sarah H. Alfaraj, Jaffar A. Al-Tawfiq, Talal A. Altuwaijri, Ziad A. Memish

《医学前沿（英文）》 2019年 第13卷 第1期   页码 126-130 doi: 10.1007/s11684-017-0603-y

摘要： Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as an important respiratory disease with high fatality rates of 40%–60%. Despite the increased number of cases over subsequent years, the number of pediatric cases remained low. A review of studies conducted from June 2012 to April 19, 2016 reported 31 pediatric MERS-CoV cases. In this paper, we present the clinical and laboratory features of seven patients with pediatric MERS. Five patients had no underlying medical illnesses, and three patients were asymptomatic. Of the seven cases, four (57%) patients sought medical advice within 1–7 days from the onset of symptoms. The three other patients (43%) were asymptomatic and were in contact with patients with confirmed diagnosis of MERS-CoV. The most common presenting symptoms were fever (57%), cough (14%), shortness of breath (14%), vomiting (28%), and diarrhea (28%). Two (28.6%) patients had platelet counts of<150 × 10 /L, and one patient had an underlying end-stage renal disease. The remaining patients presented with normal blood count, liver function, and urea and creatinine levels. The documented MERS-CoV Ct values were 32–38 for four of the seven cases. Two patients (28.6%) had abnormal chest radiographic findings of bilateral infiltration. One patient (14.3%) required ventilator support, and two patients (28.6%) required oxygen supplementation. All the seven patients were discharged without complications.

关键词： Middle East respiratory syndrome coronavirus     MERS-CoV     pregnancy     pediatrics    

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Molecular aspects of MERS-CoV

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《医学前沿（英文）》 2017年 第11卷 第3期   页码 365-377 doi: 10.1007/s11684-017-0521-z

摘要：

Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus which can cause acute respiratory distress in humans and is associated with a relatively high mortality rate. Since it was first identified in a patient who died in a Jeddah hospital in 2012, the World Health Organization has been notified of 1735 laboratory-confirmed cases from 27 countries, including 628 deaths. Most cases have occurred in Saudi Arabia. MERS-CoV ancestors may be found in Old World bats of the Vespertilionidae family. After a proposed bat to camel switching event, transmission of MERS-CoV to humans is likely to have been the result of multiple zoonotic transfers from dromedary camels. Human-to-human transmission appears to require close contact with infected persons, with outbreaks mainly occurring in hospital environments. Outbreaks have been associated with inadequate infection prevention and control implementation, resulting in recommendations on basic and more advanced infection prevention and control measures by the World Health Organization, and issuing of government guidelines based on these recommendations in affected countries including Saudi Arabia. Evolutionary changes in the virus, particularly in the viral spike protein which mediates virus-host cell contact may potentially increase transmission of this virus. Efforts are on-going to identify specific evidence-based therapies or vaccines. The broad-spectrum antiviral nitazoxanide has been shown to have in vitro activity against MERS-CoV. Synthetic peptides and candidate vaccines based on regions of the spike protein have shown promise in rodent and non-human primate models. GLS-5300, a prophylactic DNA-plasmid vaccine encoding S protein, is the first MERS-CoV vaccine to be tested in humans, while monoclonal antibody, m336 has given promising results in animal models and has potential for use in outbreak situations.

关键词： MERS-CoV     Saudi Arabia     spike protein     transmission     evolution     vaccine    

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From SARS to MERS: evidence and speculation

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《医学前沿（英文）》 2016年 第10卷 第4期   页码 377-382 doi: 10.1007/s11684-016-0466-7

摘要：

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic pathogen. In 2012, the infectious outbreak caused by MERS-CoV in Saudi Arabia has spread to more than 1600 patients in 26 countries, resulting in over 600 deaths. Without a travel history, few clinical and radiological features can reliably differentiate MERS from SARS. But in real world, comparing with SARS, MERS presents more vaguely defined epidemiology, more severe symptoms, and higher case fatality rate. In this review, we summarize the recent findings in the field of MERS-CoV, especially its molecular virology, interspecies mechanisms, clinical features, antiviral therapies, and the further investigation into this disease. As a newly emerging virus, many questions are not fully answered, including the exact mode of transmission chain, geographical distribution, and animal origins. Furthermore, a new protocol needs to be launched to rapidly evaluate the effects of unproven antiviral drugs and vaccine to fasten the clinical application of new drugs.

关键词： middle east respiratory syndrome     animal origin     cross-species transmission     monoclonal antibody    

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SARS-CoV-2 vaccine research and immunization strategies for improved control of the COVID-19 pandemic

《医学前沿（英文）》 2022年 第16卷 第2期   页码 185-195 doi: 10.1007/s11684-021-0913-y

摘要： The record speed at which Chinese scientists identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and shared its genomic sequence with the world, has greatly facilitated the development of coronavirus disease (COVID-19) diagnostics, drugs, and vaccines. It is unprecedented in pandemic control history to develop a dozen successful vaccines in the first year and to immunize over half of the global population in the second year, due to the efforts of the scientific community, biopharmaceutical industry, and regulatory agencies worldwide. The challenges are both great and multidimensional due to the rapid emergence of virus variants and waning of vaccine immunity. Vaccination strategies need to adapt to these challenges to keep population immunity above the herd immunity threshold, by increasing vaccine coverage, especially for older adults and young people, and providing timely booster doses with homologous or heterologous vaccine boosts. Further research should be undertaken to develop more effective vaccines against SARS-CoV-2 variants and to understand the best prime-boost vaccine combinations and immunization strategies to provide sufficient and sustainable immune protection against COVID-19.

关键词： COVID-19     pandemics     SARS-CoV-2     vaccination    

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SARS-CoV-2 variants, immune escape, and countermeasures

《医学前沿（英文）》 2022年 第16卷 第2期   页码 196-207 doi: 10.1007/s11684-021-0906-x

摘要： Coronavirus disease 2019 (COVID-19) has become a global pandemic disease. SARS-CoV-2 variants have aroused great concern and are expected to continue spreading. Although many countries have promoted roll-out vaccination, the immune barrier has not yet been fully established, indicating that populations remain susceptible to infection. In this review, we summarize the literature on variants of concern and focus on the changes in their transmissibility, pathogenicity, and resistance to the immunity constructed by current vaccines. Furthermore, we analyzed relationships between variants and breakthrough infections, as well as the paradigm of new variants in countries with high vaccination rates. Terminating transmission, continuing to strengthen variant surveillance, and combining nonpharmaceutical intervention measures and vaccines are necessary to control these variants.

关键词： SARS-CoV-2     COVID-19     vaccine     immune escape     breakthrough     prevention    

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ANTIVIRAL EFFECTS OF BACTERIOCIN AGAINST ANIMAL-TO-HUMAN TRANSMITTABLE MUTATED SARS-COV-2: A SYSTEMATIC

《农业科学与工程前沿（英文）》 2021年 第8卷 第4期   页码 603-622 doi: 10.15302/J-FASE -2021397

摘要：

The COVID-19 infections caused by SARS-CoV-2 have resulted in millions of people being infected and thousands of deaths globally since November 2019. To date, no unique therapeutic agent has been developed to slow the progression of this pandemic. Despite possessing antiviral traits the potential of bacteriocins to combat SARS-CoV-2 infection has not been fully investigated. This review summarizes the mechanisms by which bacteriocins can be manipulated and implemented as effective virus entry blockers with infection suppression potential properties to highly transmissible viruses through comprehensive immune modulations that are potentially effective against COVID-19. These antimicrobial peptides have been suggested as effective antiviral therapeutics and therapeutic supplements to prevent rapid virus transmission. This review also provides a new insight into the cellular and molecular alterations which have made SARS-CoV-2 self-modified with diversified infection patterns. In addition, the possible applications of antimicrobial peptides through both natural and induced mechanisms in infection prevention perspectives on changeable virulence cases are comprehensively analyzed. Specific attention is given to the antiviral mechanisms of the molecules along with their integrative use with synthetic biology and nanosensor technology for rapid detection. Novel bacteriocin based therapeutics with cutting-edge technologies might be potential substitutes for existing time-consuming and expensive approaches to fight this newly emerged global threat.

 

关键词： antimicrobial proteins / antiviral profiling of bacteriocins / antiviral therapeutics / immunomodulation / nanosensor technology / mutated SARS-CoV-2    

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Understanding risk of thrombosis with thrombocytopenia syndrome after Ad26.COV2.S vaccination

《医学前沿（英文）》 2021年 第15卷 第6期   页码 938-941 doi: 10.1007/s11684-021-0895-9

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Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination

《医学前沿（英文）》 2023年 第17卷 第4期   页码 747-757 doi: 10.1007/s11684-022-0954-x

摘要： Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

关键词： COVID-19 convalescent     SARS-CoV-2     inactivated vaccination     neutralizing antibody     B cell response    

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Persistence of humoral and cellular immune response after SARS-CoV-2 infection: opportunities and challenges

Tangchun Wu

《医学前沿（英文）》 2020年 第14卷 第6期   页码 816-819 doi: 10.1007/s11684-020-0823-4

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Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections

Rongtao Lai, Tianhui Zhou, Xiaogang Xiang, Jie Lu, Haiguang Xin, Qing Xie

《医学前沿（英文）》 2021年 第15卷 第4期   页码 644-648 doi: 10.1007/s11684-021-0847-4

摘要： The coronavirus disease 2019 (COVID-19) has caused global public health and economic crises. Thus, new therapeutic strategies and effective vaccines are urgently needed to cope with this severe pandemic. The development of a broadly neutralizing antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the attractive treatment strategies for COVID-19. Currently, the receptor-binding domain (RBD) of the spike (S) protein is the main target of neutralizing antibodies when SARS-CoV-2 enters human cells through an interaction between the S protein and the angiotensin-converting enzyme 2 expressed on various human cells. A single monoclonal antibody (mAb) treatment is prone to selective pressure due to increased possibility of targeted epitope mutation, leading to viral escape. In addition, the antibody-dependent enhancement effect is a potential risk of enhancing the viral infection. These risks can be reduced using multiple mAbs that nonoverlapping epitopes. Thus, a cocktail therapy combining two or more antibodies that recognize different regions of the viral surface may be the most effective therapeutic strategy.

关键词： neutralizing antibody     antibody cocktail     SARS-CoV-2     COVID-19     therapeutic strategy    

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Less attention paid to waterborne SARS-CoV-2 spreading in Beijing urban communities

《环境科学与工程前沿（英文）》 2021年 第15卷 第5期 doi: 10.1007/s11783-021-1398-2

摘要：

• A survey on individual’s perception of SARS-CoV-2 transmission was conducted.

关键词： Environmental dissemination     Risk communication     Individual perception    

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Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection

Yun Tan, Feng Liu, Xiaoguang Xu, Yun Ling, Weijin Huang, Mingquan Guo, Ziyu Fu, Dongguo Liang, Miao Xu, Hongzhou Lu, Saijuan Chen

《医学前沿（英文）》 2020年 第14卷 第6期   页码 746-751 doi: 10.1007/s11684-020-0822-5

摘要： The ongoing pandemic of coronavirus disease 19 (COVID-19) is caused by a newly discovered β coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination. Here we examined, using ELISA, the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6−7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection. All samples were positive for IgGs against the S- and N-proteins of SARS-CoV-2. Notably, 14 samples available at 6−7 months post-infection all showed significant neutralizing activities in a pseudovirus assay, with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2. Furthermore, in 10 blood samples from cases at 6−7 months post-infection used for memory T-cell tests, we found that interferon γ-producing CD4 and CD8 cells were increased upon SARS-CoV-2 antigen stimulation. Together, these results indicate that durable anti-SARS-CoV-2 immunity is common in convalescent population, and vaccines developed from 614D variant may offer protection from the currently predominant 614D variant of SARS-CoV-2.

关键词： SARS-CoV-2     neutralizing antibodies     T-cell response    

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Middle East respiratory syndrome coronavirus: a comprehensive review

null

《医学前沿（英文）》 2016年 第10卷 第2期   页码 120-136 doi: 10.1007/s11684-016-0430-6

摘要：

The Middle East respiratory syndrome coronavirus was first identified in 2012 and has since then remained uncontrolled. Cases have been mostly reported in the Middle East, however travel-associated cases and outbreaks have also occurred. Nosocomial and zoonotic transmission of the virus appear to be the most important routes. The infection is severe and highly fatal thus necessitating rapid and efficacious interventions. Here, we performed a comprehensive review of published literature and summarized the epidemiology of the virus. In addition, we summarized the virological aspects of the infection and reviewed the animal models used as well as vaccination and antiviral tested against it.

关键词： MERS     coronavirus     review    

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标题 作者 时间 类型 操作

中东呼吸综合征病毒（MERS-CoV）蛋白的分子特征、功能及其致病性

李艳华, 胡晨雨, 吴南屏, 姚航平, 李兰娟

期刊论文

Human monoclonal antibodies as candidate therapeutics against emerging viruses

null

期刊论文

Middle East respiratory syndrome coronavirus in pediatrics: a report of seven cases from Saudi Arabia

Sarah H. Alfaraj, Jaffar A. Al-Tawfiq, Talal A. Altuwaijri, Ziad A. Memish

期刊论文

Molecular aspects of MERS-CoV

null

期刊论文

From SARS to MERS: evidence and speculation

null

期刊论文

SARS-CoV-2 vaccine research and immunization strategies for improved control of the COVID-19 pandemic

期刊论文

SARS-CoV-2 variants, immune escape, and countermeasures

期刊论文

ANTIVIRAL EFFECTS OF BACTERIOCIN AGAINST ANIMAL-TO-HUMAN TRANSMITTABLE MUTATED SARS-COV-2: A SYSTEMATIC

期刊论文

Understanding risk of thrombosis with thrombocytopenia syndrome after Ad26.COV2.S vaccination

期刊论文

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination

期刊论文

Persistence of humoral and cellular immune response after SARS-CoV-2 infection: opportunities and challenges

Tangchun Wu

期刊论文

Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections

Rongtao Lai, Tianhui Zhou, Xiaogang Xiang, Jie Lu, Haiguang Xin, Qing Xie

期刊论文

Less attention paid to waterborne SARS-CoV-2 spreading in Beijing urban communities

期刊论文

Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection

Yun Tan, Feng Liu, Xiaoguang Xu, Yun Ling, Weijin Huang, Mingquan Guo, Ziyu Fu, Dongguo Liang, Miao Xu, Hongzhou Lu, Saijuan Chen

期刊论文

Middle East respiratory syndrome coronavirus: a comprehensive review

null

期刊论文