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[乌米芬诺尔与冠状病毒感染:研究结果与临床实践综述]

[Umifenovir and coronavirus infections: a review of research results and clinical practice].

作者信息

Leneva I A, Pshenichnaya N Y, Bulgakova V A

机构信息

Mechnikov Research Institute for Vaccines and Sera.

National Medical Research Center for Phthisiopulmonology and Infectious Diseases.

出版信息

Ter Arkh. 2020 Dec 26;92(11):91-97. doi: 10.26442/00403660.2020.11.000713.

Abstract

Coronaviruses are known to cause acute respiratory infections. Antiviral therapy, including for COVID-19, is based on clinical practice, experimental data and trial results. The purpose of this review is to: provide and systematize actual preclinical data, clinical trials results and clinical practice for antiviral agent umifenovir (Arbidol). Databases Scopus, Web of Science, RSCI and medRxiv were used for publication searching from 2004. A meta-analysis of clinical trials results was performed. Umifenovir is antiviral agent, it belongs to fusion inhibitors, interacts with SARS-CoV-2 spike protein. Umifenovir the impede the trimerization of spike glycoprotein and inhibit host cell adhesion, at the level of the coronaviruses S-protein of interaction with ACE2 receptor. Preclinical studies in vitro and on animals show umifenovir activity against a number of coronaviruses, including SARS-CoV, MERS-CoV, SARS-CoV-2, and others. Umifenovir, in combination with other antiviral drugs, symptomatic or traditional medicine, was used in China to treat patients with COVID-19, resulting in reduced mortality, virus elimination, the frequency of more severe course and complications in middle severity. However, antiviral therapy for the treatment of severe patients, with ARDS, did not lead to improved outcomes. In comparative clinical studies, umifenovir showed similar effectiveness with other antiviral drugs, and lower frequency of adverse reactions. Therapy with umifenovir, led to an increase percentage of patients with negative results of PCR tests on days 714 (I2=69.8%, RR 0.48, 95% CI 0.190.76; p=0.001). The efficacy and safety of antivirals against SARS-CoV-2 still requires clinical investigation. Moderate forms of COVID-19 could be effectively treated by antivirals, but severe forms of COVID-19, characterized by pulmonary immunopathology, require different approaches to treatment.

摘要

已知冠状病毒可引起急性呼吸道感染。包括针对新冠病毒病(COVID-19)在内的抗病毒治疗是基于临床实践、实验数据和试验结果的。本综述的目的是:提供并系统化抗病毒药物乌米芬诺尔(阿比多尔)的实际临床前数据、临床试验结果和临床实践。使用Scopus、Web of Science、俄罗斯科学引文索引(RSCI)和medRxiv数据库检索2004年以来的相关出版物。对临床试验结果进行了荟萃分析。乌米芬诺尔是一种抗病毒药物,属于融合抑制剂,可与严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白相互作用。乌米芬诺尔可在冠状病毒S蛋白与血管紧张素转换酶2(ACE2)受体相互作用的水平上阻碍刺突糖蛋白三聚化并抑制宿主细胞黏附。体外和动物实验研究表明乌米芬诺尔对包括严重急性呼吸综合征冠状病毒(SARS-CoV)、中东呼吸综合征冠状病毒(MERS-CoV)、SARS-CoV-2等多种冠状病毒具有活性。在中国,乌米芬诺尔与其他抗病毒药物、对症药物或传统药物联合用于治疗COVID-19患者,降低了死亡率、清除了病毒、减少了中重度患者病情加重和并发症的发生频率。然而,对于患有急性呼吸窘迫综合征(ARDS)的重症患者,抗病毒治疗并未改善预后。在比较临床研究中,乌米芬诺尔与其他抗病毒药物疗效相似,但不良反应发生率较低。使用乌米芬诺尔治疗使第7至14天聚合酶链反应(PCR)检测结果为阴性的患者比例增加(I2 = 69.8%,相对危险度0.48,95%置信区间0.19至0.76;p = 0.001)。抗病毒药物针对SARS-CoV-2的疗效和安全性仍需临床研究。COVID-19的中度症状形式可用抗病毒药物有效治疗,但以肺部免疫病理学为特征的COVID-19重度症状形式需要不同的治疗方法。

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