新型冠状病毒肺炎免疫治疗药物托珠单抗的回顾分析与药学监护

新型冠状病毒肺炎（COVID-19）在全球蔓延，引起世界各国高度关注。其传染性强、危害大，目前尚无确切有效的抗病毒药物。国家卫生健康委员会发布了《新型冠状病毒肺炎诊疗方案（试行第七版）》，其中首次提出了托珠单抗免疫治疗方案。检索国内外托珠单抗治疗免疫系统疾病的论文，分析托珠单抗用于治疗COVID-19重症和危重症的有效性，并从安全性角度出发，介绍诊疗方案的药物相互作用、特殊人群用药、不良反应及用药注意事项，可为COVID-19重型及危重型患者的治疗提供用药参考。     

从1例儿童新型冠状病毒普通型肺炎浅析抗病毒药物临床应用

摘要：儿童是呼吸道病毒的易感人群,儿童新型冠状病毒肺炎（COVID-19）会存在新型冠状病毒（SARS-CoV-2）与其他常见呼吸道病毒混合感染的复杂情况。目前尚无确认有效的抗SARS-CoV-2药物,因此国家诊疗方案中推荐的药物用于儿童仍需谨慎。为提高抗病毒药物在COVID-19儿童患者中应用的安全性,本文结合1例儿童COVID-19普通型病例的诊治过程,剖析该病例的抗病毒药物治疗方案,建议抗病毒药物在非重型儿童COVID-19病例的应用中需要特别关注用法用量、给药途径、疗程,以及药品不良反应的密切监测和及时处理,供儿科临床参考。     

抗病毒药物在新型冠状病毒肺炎治疗中的合理使用与药学监护

在抗击新型冠状病毒肺炎（COVID-19）疫情的关键时期,国家连续颁布了7版诊疗方案,每一新版诊疗方案对治疗药物都有补充、完善。α-干扰素、磷酸氯喹、阿比多尔、洛匹那韦/利托那韦、利巴韦林等抗病毒药物得到了临床专家的广泛认可与推荐。本文从药物不良反应、药物禁忌、药物相互作用、注意事项等多个方面对《新型冠状病毒肺炎诊疗方案（试行第七版）》涉及的抗病毒药物进行归纳与总结,对抗病毒药物的合理使用与药学监护提出建议,旨在为临床治疗药物选择提供参考,提高药物治疗效果。     

新型冠状病毒肺炎抗病毒药物的治疗现状

目的:探究新型冠状病毒肺炎抗病毒药物的治疗现状。方法:2019年12月开始,新型冠状病毒(以下简称2019-nCoV)感染引起的新型冠状病毒肺炎(COVID-19)病例在国内陆续被发现,并呈暴发趋势;2020年3月3日,国家卫生健康委员会发布的《新型冠状病毒肺炎诊疗方案(试行第7版)》中,治疗COVID-19患者的抗病毒药物主要有干扰素-α2b、洛匹那韦/利托那韦、利巴韦林、磷酸氯喹和阿比多尔。结果与结论:通过检索相关文献并结合现有临床治疗证据,评价与分析了抗病毒药物的治疗现状和优缺点,以及药学监护。     

新型冠状病毒肺炎（COVID-19）患者抗病毒用药监护的研究进展

为提高抗病毒药物在新型冠状病毒肺炎(COVID-19)患者尤其是需要多药联合患者中的合理性和安全性,结合《新型冠状病毒肺炎诊疗方案(试行第七版)》提到的抗病毒药物,通过查阅文献、搜集各抗病毒药物说明书和MCDEX合理用药信息支持系统的相关信息,总结这些抗病毒药物的临床药动学特征、药物相互作用及不良反应信息,提出合理的用药监护建议。从药动学和药物相互作用角度加强抗病毒药物在COVID-19患者中的用药监护,可提高药物使用安全性,保障患者的合理用药。     

新型冠状病毒肺炎合并肿瘤患者使用抗病毒药物的药学监护策略

摘要：为探讨治疗新型冠状病毒肺炎(COVID-19)的抗病毒药物在肿瘤患者中应用的药学监护策略,临床药师查阅相关文献资料,深度分析《新型冠状病毒感染的肺炎诊疗方案(试行第七版)》中推荐的抗病毒药物与抗肿瘤药物之间的药品不良反应(ADR)和药动学相互作用,提出了在COVID-19合并肿瘤患者中合理使用抗病毒药物的建议,旨在确保特殊人群的用药安全。     

新型冠状病毒肺炎治疗中的药物不良反应与防治

围绕《新型冠状病毒感染的肺炎诊疗方案(试行第六版)》中的治疗试用药物,包括抗病毒药物、糖皮质激素和中药,从各药的作用机制、药物相互作用、药物不良反应等方面,综述新型冠状病毒肺炎(COVID-19)治疗中可能出现的不良反应及防治策略,为临床治疗方案的合理选择提供参考。     

抗新型冠状病毒药物的研究进展

新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19)具有很强的传染性和很高的致病率.目前,对于新型冠状病毒(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)尚没有特异性的抗病毒药物,临床上根据以往抗冠状病毒用药经验以...     

抗病毒颗粒的临床研究现状

抗病毒颗粒是根据经典名方研制而成的,用于治疗上呼吸道感染及流行性感冒的独家中药复方制剂。本文综述了抗病毒颗粒在新发传染性疾病和新型冠状病毒肺炎(COVID-19)等疾病领域的临床应用潜在价值。     

新型冠状病毒肺炎合并基础疾病患者抗病毒药物使用的药学监护策略

新型冠状病毒肺炎（COVID-19）在全球暴发，已对人民的身体健康及生命安全造成了严重威胁。合并基础疾病患者易重症化，在抗病毒治疗过程中，存在加重原有疾病、发生药物相互作用及出现药物不良反应等风险，因此非常有必要结合各类基础疾病特点提供个体化的药学监护。本文综合分析COVID-19抗病毒药物在不同基础疾病中的用药风险，总结了合并用药的相互作用及可能的不良反应，为伴随心血管疾病、慢性阻塞性肺病、器官移植、艾滋病及细菌真菌感染的COVID-19患者制定了药学监护策略，旨在提高COVID-19患者治疗方案的安全、合理及有效性。     

Volatile molecules for COVID-19: A possible pharmacological strategy?

COVID-19 is a novel coronavirus disease with a higher incidence of bilateral pneumonia and pleural effusion. The high pulmonary tropism and contagiousness of the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have stimulated new approaches to combat its widespread diffusion. In developing new pharmacological strategies, the chemical characteristic of volatility can add therapeutic value to the hypothetical drug candidate. Volatile molecules are characterized by a high vapor pressure and are consequently easily exhaled by the lungs after ingestion. This feature could be exploited from a pharmacological point of view, reaching the site of action in an uncommon way but allowing for drug delivery. In this way, a hypothetical molecule for COVID-19 should have a balance between its lung exhalation characteristics and both antiviral and anti-inflammatory pharmacological action. Here, the feasibility, advantages, and disadvantages of a therapy based on oral administration of possible volatile drugs for COVID-19 will be discussed. Both aerosolized antiviral therapy and oral intake of volatile molecules are briefly reviewed, and an evaluation of 1,8-cineole is provided in view of a possible clinical use and also for asymptomatic COVID-19.     

新型冠状病毒肺炎临床治疗药物最新研究进展

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)正在世界范围内流行。作为冠状病毒,新型冠状病毒(SARS-Co V-2)和严重急性呼吸综合征冠状病毒(SARS-Co V)都通过人血管紧张素转化酶2(ACE2)受体侵入宿主细胞。面对疫情异常严峻的现状,目前尚缺乏疫苗和尚无特异性针对该病毒的抗病毒药物,临床上仍以支持治疗和对症治疗为主。本文简单介绍了新型冠状病毒和ACE2的关系及作用机制,总结了潜在抗新型冠状病毒治疗药物的最新临床疗效,及其相关药物可能的作用机制,以便充分了解COVID-19的发展过程和药物研究方向,为后续探讨COVID-19药物治疗和疫苗研发提供思路。     

Baricitinib: A Review of Pharmacology,Safety, and Emerging Clinical Experience in COVID-19

A hyperinflammatory response to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, reminiscent of cytokine release syndrome, has been implicated in the pathophysiology of acute respiratory distress syndrome and organ damage in patients with coronavirus disease 2019 (COVID-19). Agents that inhibit components of the pro-inflammatory cascade have garnered interest as potential treatment options with hopes that dampening the proinflammatory process may improve clinical outcomes. Baricitinib is a reversible Janus-associated kinase (JAK)-inhibitor that interrupts the signaling of multiple cytokines implicated in COVID-19 immunopathology. It may also have antiviral effects by targeting host factors that viruses rely for cell entry and by suppressing type I interferon driven angiotensin-converting-enzyme-2 upregulation. However, baricitinib’s immunosuppressive effects may be detrimental during acute viral infections by delaying viral clearance and increasing vulnerability to secondary opportunistic infections. The lack of reliable biomarkers to monitor patients’ immune status as illness evolves complicates deployment of immunosuppressive drugs like baricitinib. Furthermore, baricitinib carries the risk of increased thromboembolic events, which is concerning given the proclivity towards a hypercoagulable state in patients with COVID-19. In this article, we review available data on baricitinib with an emphasis on immunosuppressive and antiviral pharmacology, pharmacokinetics, safety, and current progress in COVID-19 clinical trials.     

Web resources facilitate drug discovery in treatment of COVID-19

The infectious disease Coronavirus 2019 (COVID-19) continues to cause a global pandemic and, thus, the need for effective therapeutics remains urgent. Global research targeting COVID-19 treatments has produced numerous therapy-related data and established data repositories. However, these data are disseminated throughout the literature and web resources, which could lead to a reduction in the levels of their use. In this review, we introduce resource repositories for the development of COVID-19 therapeutics, from the genome and proteome to antiviral drugs, vaccines, and monoclonal antibodies. We briefly describe the data and usage, and how they advance research for therapies. Finally, we discuss the opportunities and challenges to preventing the pandemic from developing further.     

治疗新型冠状病毒肺炎药物现有证据的文献分析

目的:对可能用于治疗新型冠状病毒肺炎(corona virus disease-19,COVID-19)的药物的现有证据进行文献检索与分析,为该病的治疗提供循证医学依据。方法:计算机检索PubMed、Clinical Trial.gov和中国临床试验注册中心官方网站,查找有关治疗COVID-19的研究。由2名研究者根据纳入与排除标准独立进行文献筛选,最后按照研究药物类别进行分类总结和分析。结果:有2项个案报道提示,瑞德西韦、洛匹那韦/利托那韦及阿比朵尔可能用于COVID-19的治疗;但1项小样本回顾性队列研究结果提示,洛匹那韦/利托那韦及阿比朵尔的疗效尚不明确;体外研究结果提示,氯喹和达芦那韦具有抗严重急性呼吸综合征冠状病毒2型(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)的活性;利巴韦林和干扰素治疗COVID-19的依据主要来源于严重急性呼吸综合征冠状病毒(severe acute respiratory syndrome coronavirus,SARS-CoV)和中东呼吸综合征冠状病毒(Middle East respiratory syndrome coronavirus,MERS-CoV)治疗的间接证据。目前,已有多项评价上述药物治疗COVID-19的疗效及安全性的随机对照试验正在进行中。结论:虽然目前COVID-19的抗病毒治疗方法尚无高质量的循证医学证据支持,但是已有多项评价中医和西医治疗方案临床疗效的研究启动,将为COVID-19的治疗提供高质量的证据支持。     

Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.     

Protein kinase C and the antiviral effect of human interferon

Protein kinase C (PKC) inhibitors: Hidaka's compounds H-7 (10 microM) and H-8 (20 microM), palmitoyl-carnitine (10 microM) and phloretin (50 microM), did not modify the antiviral effect of human natural or recombinant interferon alpha and of natural interferon beta. The tumor promoter 12-o-tetradecanoyl-phorbol-13-acetate (TPA) (200 nM), known as activator of PKC induced an antiviral state when tested on human embryo fibroblasts challenged with the vesicular stomatitis virus. The battery of PKC inhibitors used inhibited the antiviral effect induced by TPA. Palmitoyl-carnitine (10 microM) exerted a toxic effect that was reversed by interferon treatment (2,000 IU/ml interferon alpha). These results suggest that PKC, possibly activated by interferon-receptor interaction, is not essential for inducing the antiviral effect of interferon, but, probably, mediates the antiviral effect of TPA.     

新型冠状病毒肺炎诊疗方案的中药与西药比较研究

目的为临床筛选新型冠状病毒肺炎(COVID-19)治疗药物及合理用药提供参考。方法从国家及各地COVID-19诊疗方案中收集并归纳出可能有效的西药和中药,分析其在疾病各阶段的使用。结果与结论治疗COVID-19可能有效的西药是靶向抗病毒药物和抗菌药物、抗病毒药物、激素药物,以及可提高患者免疫功能药物等,可能有效的中药是抗病毒中药构成的中成药和中药方剂。     

虎杖解毒颗粒抗病毒的药效物质探究

目的探讨虎杖解毒颗粒防治新型冠状病毒肺炎的药效物质及作用机制。方法以“虎杖”“抗病毒”“冠状病毒机制”等为关键词,检索国内外相关文献,总结虎杖解毒颗粒抗病毒的药效物质、抗冠状病毒的药效物质、抗新型冠状病毒的潜在药效物质,并运用Cytoscape3.7.2软件进行分析。结果虎杖解毒颗粒抗病毒的药效物质包括板蓝根多糖、大黄素、野鸢尾苷元等53个成分,抗冠状病毒的药效物质包括白藜芦醇、大黄素、芦荟大黄素等89个成分,抗新型冠状病毒的潜在药效物质包括白藜芦醇、青蒿素、大黄素等19个成分。抗新型冠状病毒的潜在作用机制包括促进Ⅰ型干扰素抗病毒、抑制NF-κB、胞外信号调节激酶(ERK)/促分裂原活化的蛋白激酶(MAPK)、磷脂酰肌醇3激酶(PI3K)/AKT信号通路等。结论虎杖解毒颗粒中的多种成分具有抗病毒作用,其抗病毒和抗冠状病毒的机制可能与促进Ⅰ型干扰素抗病毒,以及抑制NF-κB,ERK/MAPK,PI3K/AKT信号通路有关,但需通过相关试验进行验证。     

The antiviral effect of human interferon alpha is dependent on phosphoinositide-derived messengers

Neomycin the putative blocker of membrane polyphosphoinositide hydrolysis, inhibited the antiviral activity of human interferon alpha, when tested on human quiescent fibroblasts challenged with vesicular stomatitis virus. The anti-interferon effect of neomycin could be correlated in terms of dose dependence for both neomycin (0.05-1 mM) and interferon (100-5,000 IU/ml). The results suggest that the antiviral activity of interferon alpha depends on diacylglycerol formation. Indeed, the synthetic diacylglycerol (50 microM) was as effective as 100 IU/ml interferon in inducing the antiviral state.