新冠病毒抗体药物研发进展及展望分析

抗体药物以其独特的作用机制和靶向性强、特异性好等优点,在恶性肿瘤、自身免疫性疾病、感染类疾病的诊断和治疗中发挥着越来越重要的作用,成为国际创新药物研发的热点。新冠肺炎(COVID-19)疫情发生以来,国内外多家研究机构和企业正在加快推进新冠病毒(SARS-CoV-2)抗体药物的开发。在此情势下,认真分析抗体药物现状和趋势,梳理国内外新冠病毒抗体药物研究进展,明确我国当前抗体药物创新的机遇、挑战和建议,对加快我国药物自主创新研发具有重要意义。     

新冠肺炎COVID-19临床治疗的药物选择

新型冠状病毒病COVID-19,如大多数病毒感染疾病一样,除了疫苗以外,尚无特效药,也没有针对性的治疗方法。在临床上,药物治疗主要是针对患者在感染病毒以后,免疫系统被激活到极限程度或者失去控制,从而给患者带来伤害。本研究系统地回顾了新冠肺炎爆发以来的临床治疗案例,结合中国国家卫健委发布的《新型冠状病毒病肺炎诊疗方案(试行第一至七版)》,提出了治疗新冠肺炎COVID-19临床药物的选择策略,评估了各种目前应用于临床实践的西药的疗效和风险,旨在为临床医生在药物选择上提供理论依据和临床上的案例。     

新冠肺炎遗传易感基因的研究进展

新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染人体后,个体间存在显著不同的新冠肺炎(corona virus disease 2019,COVID-19)临床症状。机体遗传因素在新冠病毒感染后的临床转归过程中发挥重要的作用。以全基因组关联研究(genome-wide association studies, GWAS)为代表的遗传关联研究方法,已成功鉴定了多个与新冠肺炎相关的易感基因,为新冠肺炎防诊治措施的研发提供了理论基础。本文综述了新冠肺炎遗传易感基因的研究进展,包括多种表型、多个人群、多种遗传变异类型的新冠肺炎全基因组关联研究以及易感基因区域的精细定位研究等,旨在为新冠肺炎遗传易感基因的后续研究提供参考。     

新冠肺炎大流行中的真菌感染CSCD

目前,新冠病毒引起的新冠肺炎全球大流行已造成4.9亿多人感染,617万多人死亡。由于新冠肺炎患者免疫力低下以及治疗药物的不良反应,机会性真菌感染明显增加,患者并发/继发真菌性感染。值得注意的是,这次新冠肺炎大流行中的真菌感染主要由曲霉、念珠菌和毛霉引起。鉴于新冠病毒高度适应人类、具有极强的传播能力以及目前市场缺乏特效药物和疫苗,在未来相当长的一段时间内,新冠病毒和真菌的合并感染将是临床医学和科学界的一个难题。     

新冠肺炎COVID-19医学影像诊断和分子检测

本研究的目的是为新冠肺炎的有效诊断及疫情后COVID-19疫情的有效检测和监控提供系统的理论依据和技术保障。本研究系统地回顾了疫情的发展,收集临床资料,分析了自疫情爆发以来,对于COVID-19感染者的临床诊断的医学影像诊断方法和分子检测技术以及临床实践中取得的经验。研究表明:临床上的疑似病例须结合流行病学接触史和影像学检查结果等临床特点进行综合分析,同时,对感染新型冠状病毒的疑似病例的呼吸道样本或血液样本进行病毒核酸检测。在临床实践中,疑似COVID-19肺炎患者不排除测试结果呈假阴性的出现,需要用实时荧光RT-PCR检测病毒核酸呈阳性才能完全确诊。     

新冠肺炎Covid-19的临床诊疗和预后管理

突如其来的新冠肺炎COVID-19疫情,对于医生、医院和医疗系统都是一次极大的挑战。从不明肺炎到确诊为新冠病毒为病原的新冠肺炎COVID-19,如何确诊病原是进一步对病人进行有效诊疗和预后的关键。本研究全面地梳理了患者的临床表现和临床分类,提出了临床诊断和临床治疗的关键点以及有效的预后管理,以期为临床医生以及医疗系统提供一个应对传染性极强、尚无疫苗可预防的新冠肺炎COVID-19。     

新冠病毒中和单克隆抗体及纳米抗体研究进展北大核心CSCD

由严重急性呼吸系统综合征冠状病毒2型(severe acute respiratory syndrome coronavirus-2,SARS-CoV-2)引起的疾病被命名为新型冠状病毒肺炎(coronavirus disease 2019,COVID-19),是一种具有强传染性、高易感性、长潜伏期的传染病。病毒刺突蛋白受体结合结构域(receptor binding domain,RBD)和细胞血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2)之间的相互作用使得SARS-CoV-2顺利进入细胞。本文对SARS-CoV-2与ACE2的相关作用机制进行了简单概述,对目前针对SARS-CoV-2中和单克隆抗体、纳米抗体的最新研究进展进行了总结,探讨了新冠肺炎的发展过程和抗体药物的研究方向,以期为包括新冠肺炎在内的新发、突发传染病中和抗体药物的研发提供参考。     

新冠肺炎疫情影响下我国水产品市场形势与后市展望

2020年,在新冠肺炎疫情影响下,水产品市场遭遇了前所未有的新情况,本研究分析2020年上半年水产养殖、市场运行、消费变化以及国际贸易的形势,并研判后期水产品市场的发展趋势。主要结论是：水产品生产存在养殖进度推迟、效益和生产积极性下降等问题,或影响后期局部品种或地区的供应,但生产基本面总体保持稳定;由于产销衔接不畅,水产品市场运行呈现量减价升的特点,随着疫情防控形势向好,价格和交易量逐步回归常年水平;水产品消费较为低迷,恢复程度不及预期,同时消费理念、渠道和形式等表现出新特征;水产品进出口贸易双双下降,出口形势严峻,进口由高速增长转入调整阶段。基于此文章提出针对性政策建议。     

COVID-19: Antiviral Agents,Antibody Development and Traditional Chinese Medicine

Virologica Sinica - The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) is the first pandemic caused by coronavirus named severe acute respiratory syndrome...     

COVID-19疫苗研究现状*

2019年底于中国武汉暴发的新型冠状病毒肺炎疫情来势凶猛,迅速蔓延全球,并被世界卫生组织列为“国际关注的突发公共卫生事件”,给全人类的健康及经济发展造成难以估量的损害。新型冠状病毒对人群普遍易感且传染性强,在无特效药物及治疗手段的情况下,疫苗接种是防控COVID-19疫情最有效且最经济的途径。目前全球疫苗研发正在加速进行,各国之间通力合作,共同应对此次疫情。主要对目前正在研发的针对SARS-CoV-2的灭活疫苗、病毒载体疫苗、基因工程重组亚单位疫苗、核酸疫苗的研究进展进行综述。     

COVID-19疫苗研究现状*

2019年底于中国武汉暴发的新型冠状病毒肺炎疫情来势凶猛,迅速蔓延全球,并被世界卫生组织列为“国际关注的突发公共卫生事件”,给全人类的健康及经济发展造成难以估量的损害。新型冠状病毒对人群普遍易感且传染性强,在无特效药物及治疗手段的情况下,疫苗接种是防控COVID-19疫情最有效且最经济的途径。目前全球疫苗研发正在加速进行,各国之间通力合作,共同应对此次疫情。主要对目前正在研发的针对SARS-CoV-2的灭活疫苗、病毒载体疫苗、基因工程重组亚单位疫苗、核酸疫苗的研究进展进行综述。     

Prolonged viral shedding and antibody persistence in patients with COVID-19

SARS-CoV-2 as a new global threat has affected global population for one year. Despite the great effort to eradicate this infection, there are still some challenges including different viral presentation, temporal immunity in infected individuals and variable data of viral shedding. We studied 255 COVID-19 suspected individuals to assess the viral shedding duration and also the antibody development against SARS-CoV-2 among the cases. Real Time RT-PCR assay was applied to determine the virus presence and SARS-CoV-2 antibodies were evaluated using SARS-CoV-2 IgM and IgG kits. 113 patients were confirmed for COVID-19 infection. The patients were followed until negative PCR achieved. The median viral shedding among studied population was obtained 34.16 (±17.65) days which was not significantly associated with age, sex and underlying diseases. Shiver and body pain were found in prolonged form of the infection and also patients who had gastrointestinal problems experienced longer viral shedding. Moreover, IgG was present in 84% of patients after 150 days. According to this data, the median viral shedding prolongation was 34.16 days which indicates that 14 days isolation might not be enough for population. In addition, IgG profiling indicated that it is persistent in a majority of patients for nearly 6 months which has brought some hopes in vaccine efficacy and application.     

Drug repurposing for SARS-CoV-2 main protease: Molecular docking and molecular dynamics investigations

The current novel corona virus illness (COVID-19) is a developing viral disease that was discovered in 2019. There is currently no viable therapeutic strategy for this illness management. Because traditional medication development and discovery has lagged behind the threat of emerging and re-emerging illnesses like Ebola, MERS-CoV, and, more recently, SARS-CoV-2. Drug developers began to consider drug repurposing (or repositioning) as a viable option to the more traditional drug development method. The goal of drug repurposing is to uncover new uses for an approved or investigational medicine that aren't related to its original use. The main benefits of this strategy are that there is less developmental risk and that it takes less time because the safety and pharmacologic requirements are met. The main protease (Mpro) of corona viruses is one of the well-studied and appealing therapeutic targets. As a result, the current research examines the molecular docking of Mpro (PDB ID: 5R81) conjugated repurposed drugs. 12,432 approved drugs were collected from ChEMBL and drugbank libraries, and docked separately into the receptor grid created on 5R81, using the three phases of molecular docking including high throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP). Based on docking scores and MM-GBSA binding free energy calculation, top three drugs (kanamycin, sulfinalol and carvedilol) were chosen for further analyses for molecular dynamic simulations.     

A global treatments for coronaviruses including COVID-19

In late December 2019 in Wuhan, China, several patients with viral pneumonia were identified as 2019 novel coronavirus (2019-nCoV). So far, there are no specific treatments for patients with coronavirus disease-19 (COVID-19), and the treatments available today are based on previous experience with similar viruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Influenza virus. In this article, we have tried to reach a therapeutic window of drugs available to patients with COVID-19. Cathepsin L is required for entry of the 2019-nCoV virus into the cell as target teicoplanin inhibits virus replication. Angiotensin-converting-enzyme 2 (ACE2) in soluble form as a recombinant protein can prevent the spread of coronavirus by restricting binding and entry. In patients with COVID-19, hydroxychloroquine decreases the inflammatory response and cytokine storm, but overdose causes toxicity and mortality. Neuraminidase inhibitors such as oseltamivir, peramivir, and zanamivir are invalid for 2019-nCoV and are not recommended for treatment but protease inhibitors such as lopinavir/ritonavir (LPV/r) inhibit the progression of MERS-CoV disease and can be useful for patients of COVID-19 and, in combination with Arbidol, has a direct antiviral effect on early replication of SARS-CoV. Ribavirin reduces hemoglobin concentrations in respiratory patients, and remdesivir improves respiratory symptoms. Use of ribavirin in combination with LPV/r in patients with SARS-CoV reduces acute respiratory distress syndrome and mortality, which has a significant protective effect with the addition of corticosteroids. Favipiravir increases clinical recovery and reduces respiratory problems and has a stronger antiviral effect than LPV/r. currently, appropriate treatment for patients with COVID-19 is an ACE2 inhibitor and a clinical problem reducing agent such as favipiravir in addition to hydroxychloroquine and corticosteroids.     

Computer modeling of a potential agent against SARS-Cov-2 (COVID-19) protease

We have modeled modifications of a known ligand to the SARS-CoV-2 (COVID-19) protease, that can form a covalent adduct, plus additional ligand-protein hydrogen bonds.     

Human Organoids as a Promising Platform for Fighting COVID-19

The coronavirus disease 2019 (COVID-19) global pandemic evoked by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a major public health problem with significant morbidity and mortality. Understanding the pathogenesis and molecular mechanisms underlying this novel virus is crucial for both fundamental research and clinical trials in order to devise effective therapies and vaccination regimens. Basic research on SARS-CoV-2 largely depends on ex vivo models that allow viral invasion and replication. Organoid models are now emerging as a valuable tool to investigate viral biology and disease progression, serving as an efficient platform to investigate potential therapies for COVID-19. Here, we summarize various human stem cell-derived organoid types employed in SARS-CoV-2 studies. We highlight key findings from these models, including cell tropisms and molecular mechanisms in viral infection. We also describe their use in identifying potential therapeutic agents against SARS-CoV-2. As more and more advanced organoids emerge, they will facilitate the understanding of disease pathogenesis for drug development in this dreaded pandemic.