Indole alkaloid sulfonic acids from an aqueous extract of Isatis indigotica roots and their antiviral activity

Six new indole alkaloid sulfonic acids (1–6), together with two analogues (7 and 8) that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica root. Their structures including the absolute configurations were determined by spectroscopic data analysis, combined with enzyme hydrolysis and comparison of experimental circular dichroism and calculated electronic circular dichroism spectra. In the preliminary assay, compounds 2 and 4 showed antiviral activity against Coxsackie virus B3 and influenza virus A/Hanfang/359/95 (H3N2), respectively.     

抗流感病毒药物的回顾、现状和展望

抗流感病毒治疗作为救治流感感染的关键手段，但目前临床可及的有效抗病毒药物仅有神经氨酸酶抑制剂（neuraminidase inhibitors，NAIs）。由于NAIs疗效的限制和耐药情况的出现，亟需研发疗效更优和耐药率更低的新型抗流感病毒药物。目前，诸多不同抗流感病毒机制的药物已处于上市前临床试验阶段。     

Current status of potential therapeutic candidates for the COVID-19 crisis

As of April 15, 2020, the ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept through 213 countries and infected more than 1,870,000 individuals, posing an unprecedented threat to international health and the economy. There is currently no specific treatment available for patients with COVID-19 infection. The lessons learned from past management of respiratory viral infections have provided insights into treating COVID-19. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been tentatively applied in clinical settings. A number of these therapies have provided substantially curative benefits in treating patients with COVID-19 infection. Furthermore, intensive research and clinical trials are underway to assess the efficacy of existing drugs and identify potential therapeutic targets to develop new drugs for treating COVID-19. Herein, we summarize the current potential therapeutic approaches for diseases related to COVID-19 infection and introduce their mechanisms of action, safety, and effectiveness.     

Monoclonal antibodies for prophylactic and therapeutic use against viral infections

Neutralizing antibodies play an essential part in antiviral immunity and are instrumental in preventing or modulating viral diseases. Polyclonal antibody preparations are increasingly being replaced by highly potent monoclonal antibodies (mAbs). Cocktails of mAbs and bispecific constructs can be used to simultaneously target multiple viral epitopes and to overcome issues of neutralization escape. Advances in antibody engineering have led to a large array of novel mAb formats, while deeper insight into the biology of several viruses and increasing knowledge of their neutralizing epitopes has extended the list of potential targets. In addition, progress in developing inexpensive production platforms will make antiviral mAbs more widely available and affordable.     

慢性乙肝患者的免疫状态与病毒载量及抗病毒疗效的关系研究

目的 探讨慢性乙肝(chronic hepatitis B,CHB)患者的机体免疫状态与病毒载量及抗病毒疗效的关系.方法 将237例CHB患者按照乙肝病毒(hepatitis B virus,HBV)载量,分为病毒阴性组、低病毒载量组和高病毒载量组,比较各组的免疫球蛋白、补体及T细胞亚群等免疫指标的差异.对其中符合抗HBV治疗指征的患者给予抗HBV治疗,观察治疗半年后的病毒学应答情况和治疗1年后的e抗原血清学应答情况,分析初始免疫状态与抗病毒疗效的关系.结果 随着HBV-DNA载量的升高,CHB患者的CD3+、CD4+及CD8+T细胞计数随之升高,而CD4+/CD8+比值随之下降(P＜0.05).完全病毒学应答组和部分/无病毒学应答组的初始免疫指标比较,差异无统计学意义(P＞0.05).获得e抗原血清学转换者与未获得e抗原血清学转换者相比,在开始抗病毒治疗时的ALT和AST水平更高(P＜0.05),但初始免疫指标差异无统计学意义(P＞0.05).结论 CHB患者的免疫状态与HBV-DNA载量相关,CD3+、CD4+及CD8+T细胞计数随着HBV-DNA载量的升高而升高,而CD4+/CD8+比值则随之下降.CHB患者在抗病毒治疗时的初始免疫状态与病毒学应答及e抗原血清学转换无明显相关性.     

2008～2013年武汉地区32家医院抗病毒药使用分析

目的:统计武汉地区近6年抗病毒药的使用情况,分析其变化趋势,为合理用药提供依据。方法:统计分析武汉地区32家医院2008~2013年抗病毒药的销售金额、用药频度(DDDs)和限定日费用(DDC)。结果:2008~2013年武汉地区抗病毒药年销售总金额和DDDs逐年上升,年销售金额排在前5位的为恩替卡韦、阿德福韦酯、拉米夫定、替比夫定和更昔洛韦;DDDs排名前5位的是阿德福韦酯、恩替卡韦、利巴韦林、替比夫定、拉米夫定。大多数药物的DDC较为稳定,个别药物如奥司他韦、穿琥宁的DDC波动较大。结论:武汉地区32家医院近6年的抗病毒药使用基本稳定,西药占据了主要市场,其中以疗效较好的恩替卡韦、价格低廉的阿德福韦酯等药品增长迅速,而穿琥宁为代表的中药抗病毒药应用较少。     

人MxA基因启动子-88/-123位多态性荧光PCR检测方法的建立及临床应用

目的 建立一套快速、灵敏和特异的人抗黏液蛋白A(MxA)基因启动子中干扰素刺激应答元件-88/-123位多态性检测体系,为合理应用IFN-α治疗慢性乙型肝炎提供分子生物学检测手段.方法 对经IFN-α治疗的患者进行HBV DNA、HBV基因分型及MxA基因启动子中干扰素刺激应答元件-88/-123位多态性位点检测,确定基因多态性与IFN-α治疗效果之间的关系.通过各种条件优化实验,建立MxA基因启动子中干扰素刺激应答元件-88/-123位多态性荧光PCR检测体系,并通过与DNA序列分析法检测结果的对比,验证荧光PCR检测体系的灵敏性及特异性,从而对该体系的临床适用性进行初步评估.采用卡方检验计算P值、回归分析法计算对比率和95%可信区间.结果 MxA基因启动子干扰素刺激应答元件中-88位为G/T杂合型和-123位为C/A杂合型者皆为IFN-α敏感型,-88位为G/G纯合型和-123位为C/C纯合型者为IFN-α不敏感型.与DNA序列分析的金标准相比,荧光PCR检测的符合率为99.65%.结论 荧光PCR检测体系,可灵敏、快捷地检测患者MxA基因多态性位点.     

磷酸奥司他韦治疗流行性感冒的临床疗效和安全性

目的 验证磷酸奥司他韦在自然获得流行性感冒(流感)患者中的临床疗效并观察其安全性和耐受性。方法 采用随机、双盲和安慰剂对照的临床试验设计。95例患者随机接受磷酸奥司他韦75mg或安慰剂治疗。结果 证实流感患者(即ITTI总体)60例，治疗组29例，对照组31例。ITTI总体治疗组疾病持续时间中位数为74．5h(95％可信区间为57．0—104．3h)，对照组疾病持续时间中位数为119．0h(95％可倍区间为90．4—138．8h)，两组疾病缓解率在统计学上差异有显著性(P＝0．0135)。ITTI总体治疗组症状总分下降值的曲线下面积中位数为1515．2，高于对照组的1233．8，但无统计学意义(P＝0．1276)。共91例可进行安全性分析，总结不良反应的发生率，治疗组和对照组无统计学差异。不良反应主要为消化系统症状。结论 磷酸奥司他韦在流感发病后早期使用，可以明显缩短疾病的持续时间、减轻症状的严重程度，而且其安全性和耐受性好。