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。     

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。     

天然产物来源的抗SARS-CoV-2药物研究进展

广谱高效的小分子药物是应对新型冠状病毒感染(COVID-19)及未来可能爆发疫情的重要武器。天然产物是药物先导化合物的重要来源,在抗COVID-19的药物研发中得到了广泛关注。本文综述了抗新型冠状病毒(SARS-CoV-2)药物的关键靶点和具有抗SARS-CoV-2活性的天然产物的研究进展,以期为抗SARS-CoV-2药物的研发提供参考。     

1例重型新型冠状病毒肺炎治愈患者的药物治疗分析

目的探讨重型新型冠状病毒肺炎(COVID-19)的临床特征,总结临床药物治疗经验。方法根据病历资料分析1例重型COVID-19患者的临床症状和药物治疗信息。结果该患者有明确的流行病学史,主要临床表现有发热、咳嗽、乏力等,指氧饱和度、电解质等实验室检查指标和胸部影像学异常,在无创呼吸机通气支持基础上,采用抗病毒、抗炎、改善呼吸功能等药物对症治疗后治愈出院。结论重型COVID-19临床表现复杂,病情进展快,可参照国家卫生健康委员会《新型冠状病毒肺炎诊疗方案》制订基本治疗措施,同时根据临床症状变化进行个体化药物对症治疗。     

ACE2与新型冠状病毒肺炎的心肾损伤

由新型冠状病毒(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染引起的新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19)不仅可以诱发典型的呼吸系统疾病,也能导致心肾系统等相关疾病。SARS-CoV-2的受体为血管紧张素转换酶2(Angiotensin-converting enzyme 2,ACE2)。本文通过阐述ACE2在心脏和肾脏中的作用,分析SARS-CoV-2感染引起患者心肾损伤的可能机制,为临床治疗COVID-19及研发抗SARS-CoV-2药物提供参考依据。     

二肽基肽酶4及其抑制剂在新型冠状病毒肺炎防治中的研究进展

新型冠状病毒肺炎(COVID-19)全球大流行给世界健康造成巨大威胁,然而到目前为止尚没有临床证实有效的治疗方法。最近研究显示二肽基肽酶4(DPP4)可能是新型冠状病毒的功能受体,然而DPP4是否直接参与新型冠状病毒与靶细胞的黏附与感染,抑制或者调节DPP4的表达与活性能否阻止COVID-19的发生发展尚需要进一步研究。以往研究显示DPP4抑制剂具有抗炎和抗纤维化作用,因此推测DPP4抑制剂可能具有抑制COVID-19患者高炎症反应状态、改善患者肺纤维化的作用,尚需临床试验加以证实。     

托珠单抗的临床应用概述及治疗新型冠状病毒肺炎的可行性探索

摘要：托珠单抗是免疫球蛋白Ig G1亚型的重组人源化抗人白细胞介素6(IL-6)受体单克隆抗体,临床用于治疗类风湿关节炎、血管炎等疾病。现有研究证明IL-6等细胞因子与新型冠状病毒肺炎(COVID-19)病情恶化相关。本文系统介绍托珠单抗的临床治疗特点、安全性、药物相互作用以及在COVID-19治疗中的应用。     

新型冠状病毒肺炎与传染性非典型肺炎特点及药物治疗的对比分析

2019年12月在中国武汉陆续发现多例新型冠状病毒肺炎(corona virus disease 2019,COVID-19)患者,并迅速在全世界范围内造成了严重疫情。因此针对COVID-19的研究成为热点。目前尚没有针对COVID-19的特效药物或疫苗。引起COVID-19的严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)和2003年在中国引起传染性非典型肺炎(severe acute respiratory syndrome,SARS)的病毒(severe acute respiratory syndrome coronavirus,SARS-CoV)都属于冠状病毒,有许多相似之处。本文从流行病学、病原学、临床表现、药物治疗4个方面对2次疫情进行了系统的比较分析,详细对比了2次疫情的治疗方案,并整理出当前临床药物治疗方案以及一些具有临床治疗前景的药物,以方便临床医疗团队能够借鉴SARS治疗的经验和教训,顺利开展COVID-19的治疗。     

法匹拉韦治疗新冠肺炎临床研究进展

新型冠状病毒肺炎(COVID-19)疫情在全球大流行,临床上迫切需要特异性抗病毒治疗药物。对已批准上市或正在临床开发的药物开展重定位研究是针对突发疫情快速寻找潜在治疗药物最为快速和高效的策略。法匹拉韦是一种广谱抗RNA病毒药物,在日本和中国已批准上市用于治疗流感,其作为抗新型冠状病毒感染的潜在药物,全球多个国家正在开展相关临床试验,初步的结果令人鼓舞。本文主要综述在中国、日本、俄罗斯和印度等国家开展的法匹拉韦单用或联合其他药物治疗COVID-19的临床试验,考察用药剂量、试验设计、药物有效性和安全性等。研究结果显示,法匹拉韦在针对COVID-19轻症和中症患者的治疗中,能够有效提高患者病毒RNA清除率或改善临床恢复率,且表现出良好的安全性。本文对法匹拉韦治疗COVID-19临床研究进展进行总结,为其在抗COVID-19治疗中的应用提供参考。     

儿童新型冠状病毒肺炎药物治疗研究进展

新型冠状病毒(severe acute respiratory syndrome corona virus,SARS-CoV)-2感染在全球暴发,目前尚无明确有效的抗病毒药物治疗SARS-CoV-2感染。结合以往临床一线治疗新型冠状病毒肺炎(corona virus disease 2019,COVID-19)的经验,从核苷类似物、蛋白酶抑制剂等抗病毒药物、免疫相关药物及恢复期血浆治疗等方面,本文就儿童COVID-19药物治疗研究进展作一综述。     

Importance of early precautionary actions in avoiding the spread of COVID-19: Saudi Arabia as an Example

Late in 2019, several cases of infection with a new strain of coronavirus were reported in China. This new strain was later officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the World Health Organization (WHO). This new virus (SARS-CoV2-) mainly affects the respiratory system and causes coronavirus disease 2019 (COVID-19). The first case of COVID-19 was reported to the WHO on December 31st, 2019, and the virus has spread dramatically in many countries worldwide. On March 11th, 2020, the WHO declared that COVID-19 had affected most of the world, and many deaths were linked to COVID-19. Unfortunately, there is no available treatment for COVID-19, and there is no available vaccine against SARS-CoV-2. Thus, preventive methods are the only way to limit the spread of the virus. Preventive actions have been taken by many countries, such as travel bans, closing borders and working from home. Saudi Arabia was one of the countries that took very early precautionary actions in the belief that these actions are the best way to fight the virus. Therefore, we present the actions that were taken by the Kingdom of Saudi Arabia to fight the new viral pandemic.     

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak and is a major public health issue. As of 11 February 2020, data from the World Health Organization (WHO) have shown that more than 43 000 confirmed cases have been identified in 28 countries/regions, with >99% of cases being detected in China. On 30 January 2020, the WHO declared COVID-19 as the sixth public health emergency of international concern. SARS-CoV-2 is closely related to two bat-derived severe acute respiratory syndrome-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. It is spread by human-to-human transmission via droplets or direct contact, and infection has been estimated to have mean incubation period of 6.4 days and a basic reproduction number of 2.24–3.58. Among patients with pneumonia caused by SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough. Bilateral lung involvement with ground-glass opacity was the most common finding from computed tomography images of the chest. The one case of SARS-CoV-2 pneumonia in the USA is responding well to remdesivir, which is now undergoing a clinical trial in China. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary intervention being used. However, public health authorities should keep monitoring the situation closely, as the more we can learn about this novel virus and its associated outbreak, the better we can respond.     

The concern about ACE/ARB and COVID-19: Time to hold your horses!

Concern about coronavirus 2019 (COVID-19) morbidity and mortality has drawn attention to the potential role of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) because the SARS-CoV-2 uses the ACE2 receptor as its point of entry into the body. It is not clear if and to what degree the SARS-CoV-2 virus affects the renin-angoiotensin system. Early studies from China which speculated on the role of ACE inhibition and ARBs did not evaluate the drug regimens. A vast body of evidence supports the use of ACE inhibitors and ARBs in hypertensive patients and patients with heart failure, and very little evidence has been acquired about their role in COVID-19. There is good evidence in support of the use of ACE inhibitors and ARBs in indicated patients with hypertension and heart failure, and clinicians should be reticent about abruptly withdrawing these drugs based on a paucity of evidence.     

Differential Signaling and Virus Production in Calu-3 Cells and Vero Cells upon SARS-CoV-2 Infection

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Signaling pathways that are essential for virus production have potential as therapeutic targets against COVID-19. In this study, we investigated cellular responses in two cell lines, Vero and Calu-3, upon SARS-CoV-2 infection and evaluated the effects of pathway-specific inhibitors on virus production. SARS-CoV-2 infection induced dephosphorylation of STAT1 and STAT3, high virus production, and apoptosis in Vero cells. However, in Calu-3 cells, SARS-CoV-2 infection induced long-lasting phosphorylation of STAT1 and STAT3, low virus production, and no prominent apoptosis. Inhibitors that target STAT3 phosphorylation and dimerization reduced SARS-CoV-2 production in Calu-3 cells, but not in Vero cells. These results suggest a necessity to evaluate cellular consequences upon SARS-CoV-2 infection using various model cell lines to find out more appropriate cells recapitulating relevant responses to SARS-CoV-2 infection in vitro.     

新型冠状病毒(SARS-CoV-2)的起源和检测方法

自2019年12月,中国武汉爆发了新型冠状病毒(SARS-CoV-2)导致的新型冠状病毒肺炎(COVID-19),截至2020年2月26日,已导致累计78 190人确诊感染,超过2 700人死亡,除中国外,亚洲、北美、欧洲、非洲等已有20多个国家发现新型冠状病毒确诊病例。中国疾病预防控制中心研究结果表明,无症状感染者的比例占1.2%,这些无症状传染者在潜伏期很可能具有传染性。确定SARS-CoV-2的起源和了解目前常见的检测方法,将对战胜这次疫情以及日后防范其卷土重来至关重要。     

查尔酮及其衍生物防治新型冠状病毒肺炎（COVID-2019）潜在应用的研究进展

新型冠状病毒肺炎(COVID-2019)自发生以来,疫情进展迅速,严重威胁人们的身体健康。目前,临床上尚无针对其治疗的特效药物,多数为对症治疗,以延缓新型冠状病毒引起的机体损伤为主,因此,寻找安全有效的治疗药物成为刻不容缓的工作。查尔酮及其衍生物具有广泛的药理学作用,可发挥抗病毒、抗菌抗炎、抗氧化、抗纤维等多种作用。主要对查尔酮及其衍生物的药理作用和机制进行综述,并对其用于COVID-2019防治的可行性进行探讨,以期为临床治疗提供参考。     

A Novel Therapeutic Peptide Blocks SARS-CoV-2 Spike Protein Binding with Host Cell ACE2 Receptor

Background and ObjectiveCoronavirus disease 2019 is a novel disease caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus. It was first detected in December 2019 and has since been declared a pandemic causing millions of deaths worldwide. Therefore, there is an urgent need to develop effective therapeutics against coronavirus disease 2019. A critical step in the crosstalk between the virus and the host cell is the binding of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to the peptidase domain of the angiotensin-converting enzyme 2 (ACE2) receptor present on the surface of host cells.MethodsAn in silico approach was employed to design a 13-amino acid peptide inhibitor (13AApi) against the RBD of the SARS-CoV-2 spike protein. Its binding specificity for RBD was confirmed by molecular docking using pyDockWEB, ClusPro 2.0, and HDOCK web servers. The stability of 13AApi and the SARS-CoV-2 spike protein complex was determined by molecular dynamics simulation using the GROMACS program while the physicochemical and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of 13AApi were determined using the ExPASy tool and pkCSM server. Finally, in vitro validation of the inhibitory activity of 13AApi against the spike protein was performed by an enzyme-linked immunosorbent assay.ResultsIn silico analyses indicated that the 13AApi could bind to the RBD of the SARS-CoV-2 spike protein at the ACE2 binding site with high affinity. In vitro experiments validated the in silico findings, showing that 13AApi could significantly block the RBD of the SARS-CoV-2 spike protein.ConclusionsBlockage of binding of the SARS-CoV-2 spike protein with ACE2 in the presence of the 13AApi may prevent virus entry into host cells. Therefore, the 13AApi can be utilized as a promising therapeutic agent to combat coronavirus disease 2019.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40268-021-00357-0.     

Antiviral Efficacy of Pralatrexate against SARS-CoV-2

Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global community. However, only limited access has been allowed to COVID-19 vaccines and antiviral treatment options. Here, we report the efficacy of the anticancer drug pralatrexate against SARS-CoV-2. In Vero and human lung epithelial Calu-3 cells, pralatrexate reduced viral RNA copies of SARS-CoV-2 without detectable cytotoxicity, and viral replication was successfully inhibited in a dose-dependent manner. In a time-to-addition assay, pralatrexate treatment at almost half a day after infection also exhibited inhibitory effects on the replication of SARS-CoV-2 in Calu-3 cells. Taken together, these results suggest the potential of pralatrexate as a drug repurposing COVID-19 remedy.     

Application of microfluidic technologies on COVID-19 diagnosis and drug discovery

The ongoing coronavirus disease 2019 (COVID-19) pandemic has boosted the development of antiviral research. Microfluidic technologies offer powerful platforms for diagnosis and drug discovery for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis and drug discovery. In this review, we introduce the structure of SARS-CoV-2 and the basic knowledge of microfluidic design. We discuss the application of microfluidic devices in SARS-CoV-2 diagnosis based on detecting viral nucleic acid, antibodies, and antigens. We highlight the contribution of lab-on-a-chip to manufacturing point-of-care equipment of accurate, sensitive, low-cost, and user-friendly virus-detection devices. We then investigate the efforts in organ-on-a-chip and lipid nanoparticles (LNPs) synthesizing chips in antiviral drug screening and mRNA vaccine preparation. Microfluidic technologies contribute to the ongoing SARS-CoV-2 research efforts and provide tools for future viral outbreaks.