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在爆发病例中的治疗策略,是治疗源自中国武汉的新型冠状

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发表于 2020-2-3 11:47 |显示全部帖子
Opinion Article
Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China [version 1; peer review: awaiting peer review]
Robert L. Kruse
https://orcid.org/0000-0002-8669-6242
Author details

This article is included in the Disease Outbreaks gateway.
Abstract
A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019 -nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treat ment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain, providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year (s).
Keywords

coronavirus, Wuhan, neutralizing antibody, ACE2, outbreak, 2019-nCoV

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发表于 2020-2-3 11:47 |显示全部帖子
意见文章
在爆发病例中的治疗策略,是治疗源自中国武汉的新型冠状病毒[1版]。同行评审:等待同行评审]
罗伯特·克鲁斯
https://orcid.org/0000-0002-8669-6242
作者详情

本文包含在疾病爆发网关中。
抽象
起源于中国武汉的新型冠状病毒(2019-nCoV)对世界人口构成潜在的呼吸道病毒大流行。当前的工作集中在对感染者的围堵和隔离。最终,可以通过保护性疫苗来控制暴发,以预防2019年-nCoV感染。尽管应大力开展疫苗研究,但尽管迫切需要寻找帮助这些患者并避免潜在死亡的选择,但目前尚无治疗感染后2019-nCoV的疗法。在此,我回顾了治疗患者2019-nCoV的潜在选择,重点强调了在这种暴发中开发新的有效疗法的速度和及时性的必要性。我考虑了药物调整用途,开发中和性单克隆抗体疗法以及针对病毒RNA基因组的寡核苷酸策略的选择,强调了这些方法的前景和缺陷。最后,我主张现在就开发一种治疗方法的最快策略,该策略可以抵抗病毒将来可能发生的任何突变。该提案是一种生物制剂,可通过使用可溶形式的病毒受体血管紧张素转化酶2(ACE2)与免疫球蛋白Fc结构域融合来阻止2019-nCoV进入,从而提供最大呼吸的中和抗体以避免任何病毒逃逸,同时还有助于募集免疫系统以建立持久的免疫力。 ACE2-Fc蛋白的序列已提供给研究人员,从而使其有可能在重组蛋白表达系统中使用,今天开始生产药物以同情使用来治疗患者,而随后进行了正式的临床试验。在开发保护性疫苗并在未来数月至数年内广泛使用这种治疗方法之前,可以帮助感染患者。
关键词

冠状病毒,武汉,中和抗体,ACE2,爆发,2019-nCoV

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发表于 2020-2-3 11:50 |显示全部帖子

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发表于 2020-2-4 23:33 |显示全部帖子
不知道现有核苷类例如替诺福韦药物对这种rna病毒有没有抑制效果

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发表于 2020-2-5 09:09 |显示全部帖子
Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
Dear Editor,

In December 2019, a novel pneumonia caused by a previously unknown pathogen emerged in Wuhan, a city of 11 million people in central China. The initial cases were linked to exposures in a seafood market in Wuhan.1 As of January 27, 2020, the Chinese authorities reported 2835 confirmed cases in mainland China, including 81 deaths. Additionally, 19 confirmed cases were identified in Hong Kong, Macao and Taiwan, and 39 imported cases were identified in Thailand, Japan, South Korea, United States, Vietnam, Singapore, Nepal, France, Australia and Canada. The pathogen was soon identified as a novel coronavirus (2019-nCoV), which is closely related to sever acute respiratory syndrome CoV (SARS-CoV).2 Currently, there is no specific treatment against the new virus. Therefore, identifying effective antiviral agents to combat the disease is urgently needed.

An efficient approach to drug discovery is to test whether the existing antiviral drugs are effective in treating related viral infections. The 2019-nCoV belongs to Betacoronavirus which also contains SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). Several drugs, such as ribavirin, interferon, lopinavir-ritonavir, corticosteroids, have been used in patients with SARS or MERS, although the efficacy of some drugs remains controversial.3 In this study, we evaluated the antiviral efficiency of five FAD-approved drugs including ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine and two well-known broad-spectrum antiviral drugs remdesivir (GS-5734) and favipiravir (T-705) against a clinical isolate of 2019-nCoV in vitro.

Standard assays were carried out to measure the effects of these compounds on the cytotoxicity, virus yield and infection rates of 2019-nCoVs. Firstly, the cytotoxicity of the candidate compounds in Vero E6 cells (ATCC-1586) was determined by the CCK8 assay. Then, Vero E6 cells were infected with nCoV-2019BetaCoV/Wuhan/WIV04/20192 at a multiplicity of infection (MOI) of 0.05 in the presence of varying concentrations of the test drugs. DMSO was used in the controls. Efficacies were evaluated by quantification of viral copy numbers in the cell supernatant via quantitative real-time RT-PCR (qRT-PCR) and confirmed with visualization of virus nucleoprotein (NP) expression through immunofluorescence microscopy at 48 h post infection (p.i.) (cytopathic effect was not obvious at this time point of infection). Among the seven tested drugs, high concentrations of three nucleoside analogs including ribavirin (half-maximal effective concentration (EC50) = 109.50 μM, half-cytotoxic concentration (CC50) > 400 μM, selectivity index (SI) > 3.65), penciclovir (EC50 = 95.96 μM, CC50 > 400 μM, SI > 4.17) and favipiravir (EC50 = 61.88 μM, CC50 > 400 μM, SI > 6.46) were required to reduce the viral infection (Fig. 1a and Supplementary information, Fig. S1). However, favipiravir has been shown to be 100% effective in protecting mice against Ebola virus challenge, although its EC50 value in Vero E6 cells was as high as 67 μM,4 suggesting further in vivo studies are recommended to evaluate this antiviral nucleoside. Nafamostat, a potent inhibitor of MERS-CoV, which prevents membrane fusion, was inhibitive against the 2019-nCoV infection (EC50 = 22.50 μM, CC50 > 100 μM, SI > 4.44). Nitazoxanide, a commercial antiprotozoal agent with an antiviral potential against a broad range of viruses including human and animal coronaviruses, inhibited the 2019-nCoV at a low-micromolar concentration (EC50 = 2.12 μM; CC50 > 35.53 μM; SI > 16.76). Further in vivo evaluation of this drug against 2019-nCoV infection is recommended. Notably, two compounds remdesivir (EC50 = 0.77 μM; CC50 > 100 μM; SI > 129.87) and chloroquine (EC50 = 1.13 μM; CC50 > 100 μM, SI > 88.50) potently blocked virus infection at low-micromolar concentration and showed high SI (Fig. 1a, b).

Remdesivir has been recently recognized as a promising antiviral drug against a wide array of RNA viruses (including SARS/MERS-CoV5) infection in cultured cells, mice and nonhuman primate (NHP) models. It is currently under clinical development for the treatment of Ebola virus infection.6 Remdesivir is an adenosine analogue, which incorporates into nascent viral RNA chains and results in pre-mature termination.7 Our time-of-addition assay showed remdesivir functioned at a stage post virus entry (Fig. 1c, d), which is in agreement with its putative anti-viral mechanism as a nucleotide analogue. Warren et al. showed that in NHP model, intravenous administration of 10 mg/kg dose of remdesivir resulted in concomitant persistent levels of its active form in the blood (10 μM) and conferred 100% protection against Ebola virus infection.7 Our data showed that EC90 value of remdesivir against 2019-nCoV in Vero E6 cells was 1.76 μM, suggesting its working concentration is likely to be achieved in NHP. Our preliminary data (Supplementary information, Fig. S2) showed that remdesivir also inhibited virus infection efficiently in a human cell line (human liver cancer Huh-7 cells), which is sensitive to 2019-nCoV.2

Chloroquine, a widely-used anti-malarial and autoimmune disease drug, has recently been reported as a potential broad-spectrum antiviral drug.8,9 Chloroquine is known to block virus infection by increasing endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors of SARS-CoV.10 Our time-of-addition assay demonstrated that chloroquine functioned at both entry, and at post-entry stages of the 2019-nCoV infection in Vero E6 cells (Fig. 1c, d). Besides its antiviral activity, chloroquine has an immune-modulating activity, which may synergistically enhance its antiviral effect in vivo. Chloroquine is widely distributed in the whole body, including lung, after oral administration. The EC90 value of chloroquine against the 2019-nCoV in Vero E6 cells was 6.90 μM, which can be clinically achievable as demonstrated in the plasma of rheumatoid arthritis patients who received 500 mg administration.11 Chloroquine is a cheap and a safe drug that has been used for more than 70 years and, therefore, it is potentially clinically applicable against the 2019-nCoV.

Our findings reveal that remdesivir and chloroquine are highly effective in the control of 2019-nCoV infection in vitro. Since these compounds have been used in human patients with a safety track record and shown to be effective against various ailments, we suggest that they should be assessed in human patients suffering from the novel coronavirus disease.
Gilead Sciences Statement on the Company’s Ongoing Response to the 2019 Novel Coronavirus (2019-nCoV)

Foster City, Calif., January 31, 2020 — Gilead Sciences today issued the following statement from Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences:

"Gilead is working closely with global health authorities to respond to the novel coronavirus (2019-nCoV) outbreak through the appropriate experimental use of our investigational compound remdesivir. Together with the U.S. Food and Drug Administration (FDA), the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Department of Health and Human Services (DHHS), the China CDC and National Medical Product Administration (NMPA), the World Health Organization (WHO), and the U.S. National Institute of Allergies and Infectious Diseases (NIAID), and along with individual researchers and clinicians, Gilead is focused on contributing our antiviral expertise and resources to help patients and communities fighting 2019-nCoV.

Remdesivir is not yet licensed or approved anywhere globally and has not been demonstrated to be safe or effective for any use. At the request of treating physicians, and with the support of local regulatory agencies, who have weighed the risks and benefits of providing an experimental drug with no data in 2019-nCoV, Gilead has provided remdesivir for use in a small number of patients with 2019-nCoV for emergency treatment in the absence of any approved treatment options.

Gilead is working with health authorities in China to establish a randomized, controlled trial to determine whether remdesivir can safely and effectively be used to treat 2019-nCoV. We are also expediting appropriate laboratory testing of remdesivir against 2019-nCoV samples.

While there are no antiviral data for remdesivir that show activity against 2019-nCoV at this time, available data in other coronaviruses give us hope. Remdesivir has demonstrated in vitro and in vivo activity in animal models against the viral pathogens MERS and SARS, which are coronaviruses that are structurally similar to 2019-nCoV. There are also limited clinical data available from the emergency use of remdesivir in the treatment of patients with Ebola virus infection.

Gilead is committed to supporting the global health community to quickly and effectively respond to serious and life-threatening viral outbreaks worldwide."
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发表于 2020-2-5 09:11 |显示全部帖子
Remdesivir和chloroquine在体外有效抑制最近出现的新型冠状病毒(2019-nCoV)
亲爱的编辑,

2019年12月,在中国中部一千一百万人口的城市武汉,出现了一种由先前未知的病原体引起的新型肺炎。最初的病例与武汉海产品市场的暴露有关。 1截至2020年1月27日,中国当局报告了中国大陆2835例确诊病例,包括81例死亡。此外,在香港,澳门和台湾发现了19例确诊病例,在泰国,日本,韩国,美国,越南,新加坡,尼泊尔,法国,澳大利亚和加拿大发现了39例进口病例。该病原体很快被鉴定为新型冠状病毒(2019-nCoV),与严重急性呼吸系统综合症冠状病毒(SARS-CoV)密切相关。 2目前,尚无针对新病毒的特殊治疗方法。因此,迫切需要找到有效的抗病毒药物来对抗这种疾病。

一种有效的药物发现方法是测试现有的抗病毒药物在治疗相关病毒感染方面是否有效。 2019-nCoV属于Betacoronavirus,也包含SARS-CoV和中东呼吸综合征CoV(MERS-CoV)。 SARS或MERS患者使用了几种药物,例如利巴韦林,干扰素,洛匹那韦-利托那韦,皮质类固醇,尽管某些药物的疗效仍存在争议。 3在这项研究中,我们评估了五种经过FAD批准的药物的抗病毒效果,其中包括利巴韦林,喷昔洛韦,硝唑尼特,那法莫司他,氯喹和两种著名的广谱抗病毒药伦德昔韦(GS-5734)和法维吡韦(T-705)对临床分离的2019-nCoV。

进行标准测定以测量这些化合物对2019-nCoV的细胞毒性,病毒产量和感染率的影响。首先,通过CCK8分析确定候选化合物在Vero E6细胞(ATCC-1586)中的细胞毒性。然后,在存在不同浓度的测试药物的情况下,以0.05的感染复数(MOI)用nCoV-2019BetaCoV /武汉/ WIV04 / 20192感染Vero E6细胞。在对照中使用DMSO。通过定量实时RT-PCR(qRT-PCR)定量细胞上清液中的病毒拷贝数来评估功效,并在感染后(pi)48小时通过免疫荧光显微镜通过可视化病毒核蛋白(NP)的表达进行确认(细胞病变)在感染的此时效果不明显)。在这7种受试药物中,高浓度的三种核苷类似物包括利巴韦林(半最大有效浓度(EC50)= 109.50μM,半细胞毒性浓度(CC50)> 400μM,选择性指数(SI)> 3.65),喷昔洛韦( EC50 = 95.96μM,CC50> 400μM,SI> 4.17)和favipiravir(EC50 = 61.88μM,CC50> 400μM,SI> 6.46)可以减少病毒感染(图1a和补充信息,图S1)。然而,尽管依维拉韦在Vero E6细胞中的EC50值高达67μM,但已显示出100%的有效保护小鼠抵抗埃博拉病毒攻击的能力[4],建议进一步进行体内研究以评估这种抗病毒核苷。一种有效的MERS-CoV抑制剂,可防止膜融合,对2019-nCoV感染具有抑制作用(EC50 = 22.50μM,CC50> 100μM,SI> 4.44)。一系列病毒,包括人类动物冠状病毒在低微摩尔浓度(EC50 = 2.12μM; CC50> 35.53μM; SI> 16.76)。建议对该药物针对2019-nCoV感染进行进一步的体内评估。值得注意的是,两种化合物瑞德昔韦(EC50 = 0.77μM; CC50> 100μM; SI> 129.87)和氯喹(EC50 = 1.13)μM; CC50> 100μM,SI> 88.50)可在低微摩尔浓度下有效阻断病毒感染,并显示出较高的SI(图1a,b)。
Remdesivir最近被公认为是针对培养细胞,小鼠和非人类灵长类动物(NHP)模型中的多种RNA病毒(包括SARS / MERS-CoV5)感染的有前途的抗病毒药物。目前正在临床研究中,用于治疗埃博拉病毒感染。6Remdesivir是一种腺苷类似物,可整合到新生的病毒RNA链中并导致过早终止。7我们的加药时间分析表明remdesivir在一个阶段起作用病毒进入后(图1c,d),与其作为核苷酸类似物的推定的抗病毒机制是一致的。沃伦等。结果表明,在NHP模型中,静脉内施用10μmg/ kg剂量的瑞德昔韦可导致其活性形式在血液中持续存在水平(10μm),并提供100%的埃博拉病毒感染防护。7我们的数据表明,EC90值在Vero E6细胞中针对2019-nCoV的瑞德昔韦为1.76μmM,表明在NHP中可能达到其工作浓度。我们的初步数据(补充信息,图S2)表明,雷姆昔韦还可以有效抑制人细胞系(人肝癌Huh-7细胞)中的病毒感染,该细胞系对2019-nCoV.2敏感

氯喹是一种广泛使用的抗疟疾和自身免疫性疾病药物,最近被报道为潜在的广谱抗病毒药物。8,9氯喹通过增加病毒/细胞融合所需的内体pH来阻断病毒感染。干扰SARS-CoV细胞受体的糖基化反应。10我们的加药时间分析表明,氯喹在Vero E6细胞中在2019-nCoV感染的进入和进入后阶段均起作用(图1c, d)。除其抗病毒活性外,氯喹还具有免疫调节活性,可在体内协同增强其抗病毒作用。口服后,氯喹广泛分布于整个身体,包括肺。氯喹对Vero E6细胞中2019-nCoV的EC90值为6.90μm,在接受500μmg类风湿性关节炎患者的血浆中可证明是临床可实现的11.氯喹是一种便宜且安全的药物使用了70多年,因此,它可能在临床上适用于2019-nCoV。

我们的发现表明,雷姆昔韦和氯喹在体外控制2019-nCoV感染方面非常有效。由于这些化合物已用于具有安全跟踪记录的人类患者,并且显示出对各种疾病的功效,因此我们建议应在患有新型冠状病毒疾病的人类患者中对它们进行评估。
吉利德科学公司(Gilead Sciences)关于公司对2019年新型冠状病毒的持续回应的声明(2019-nCoV)

加利福尼亚州福斯特城,2020年1月31日-吉利德科学公司今天发表了吉利德科学公司首席医学官医学博士Merdad Parsey的以下声明:

“吉勒德正在与全球卫生当局密切合作,通过适当地实验性使用我们的研究化合物瑞姆昔韦来应对新型冠状病毒(2019-nCoV)的爆发。与美国食品药品监督管理局(FDA),美国疾病控制中心一起和预防(CDC),美国卫生与公共服务部(DHHS),中国CDC和国家医疗产品管理局(NMPA),世界卫生组织(WHO)以及美国国家过敏和传染病研究所(NIAID) ),并与个人研究人员和临床医生一起,吉利德专注于贡献我们的抗病毒专业知识和资源,以帮助抗击2019-nCoV的患者和社区。

Remdesivir尚未在全球任何地方获得许可或批准,并且尚未证明对任何用途都是安全或有效的。应主治医师的要求,并在当地监管机构的支持下(权衡了在2019-nCoV中提供无数据的实验药物的风险和益处),吉利德提供了remdesivir供2019年的少数患者使用-nCoV在没有任何批准的治疗方案的情况下用于紧急治疗。

吉利德(Gilead)正在与中国卫生部门合作建立一项随机对照试验,以确定雷姆昔韦是否可以安全有效地用于治疗2019-nCoV。我们还将加快针对2019-nCoV样品的瑞德昔韦的适当实验室测试。

虽然目前尚无瑞姆昔韦的抗病毒数据显示其对2019-nCoV的活性,但其他冠状病毒的可用数据给了我们希望。伦德西韦已在动物模型中证明了对病毒病原体MERS和SARS的体外和体内活性,所述病毒病原体是与2019-nCoV结构相似的冠状病毒。紧急使用雷姆昔韦治疗埃博拉病毒感染患者的临床数据也有限。

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发表于 2020-2-5 10:51 |显示全部帖子
病急乱投医

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发表于 2020-2-6 15:50 |显示全部帖子
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to hiv, HCV/HIV, undefined, Natap
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Coronavirus: Gilead’s Remdesivir Begins Trials as Researchers Publish Positive In Vitro Results
By
Alex Philippidis
-
February 5, 2020

Clinical trials of Gilead Sciences’ remdesivir have begun in Wuhan, China, the center of the novel coronavirus outbreak, a day after Chinese researchers recommended that the antiviral drug candidate remdesivir be assessed in humans as a potential treatment for 2019-nCoV

Clinical trials of Gilead Sciences’ remdesivir have begun in Wuhan, China, the center of the novel coronavirus outbreak, a day after Chinese researchers recommended that the antiviral drug candidate remdesivir be assessed in humans as a potential treatment for 2019-nCoV.

China’s National Medical Products Administration has approved applications by the China-Japan Friendship Hospital and the Chinese Academy of Medical Sciences to conduct trials evaluating remdesivir.

Today, China’s state-owned Xinhua news agency reported that Friendship Hospital plans to study a total of 761 patients in two trials—one trial to assess 308 with mild or moderate infection, the other 453 severely infected patients—at Jinyintan Hospital in Wuhan, under Phase III studies that have been officially launched.

“We hope good results will be achieved in the trials,” said , deputy director of the science and technology ministry’s China Biotechnology Development Center, at a press conference held by the National Health Commission.

According to updated coronavirus figures reported today by the National Health Commission, 65 people died and 3,887 more people were confirmed to be infected on Tuesday. To date, 24,324 people have been confirmed as infected with 2019-nCoV, and 490 people have died—more than the 349 who died in the SARS outbreak of 2002–03—with 892 patients cured and discharged from hospitals.

China has launched numerous initiatives in recent days aimed at controlling the outbreak, with Xinhua reporting today that President Xi Jinping said “the infection prevention and control is at a critical moment and stressed the utmost importance of carrying out the work in a law-based, scientific and orderly manner,” during the third meeting of the Commission for Overall Law-based Governance of the Communist Party of China Central Committee, headed by Xi.

Xi also signaled that China may hold some officials accountable for the nation’s initial slow response to containing 2019-nCoV: “Xi spoke of the need to improve legislation related to epidemic prevention and control, strengthen the building of supporting institutions and improve punishment procedures.” He has previously characterized China’s initial response as marked by “shortcomings and deficiencies.”
Remdesivir, chloroquine “highly effective”

The trials were announced as having begun a day after the experimental drug and a marketed anti-malarial, chloroquine, showed promising preclinical results.

“Our findings reveal that remdesivir and chloroquine are highly effective in the control of 2019-nCoV infection in vitro,” the researchers reported in “Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro,” a study published as a letter to the editor of the Nature-owned journal Cell Research.

“Since these compounds have been used in human patients with a safety track record and shown to be effective against various ailments, we suggest that they should be assessed in human patients suffering from the novel coronavirus disease,” the researchers added.

The research team consisted of investigators from the Wuhan Institute of Virology, Chinese Academy of Sciences / National Center for Biosafety and the National Academy of Military Medical Research Institute of Emergency Medicine for Prevention and Control of Drugs.

The researchers published their recommendation Tuesday, the same day that China’s Ministry of Science and Technology first said it would launch human clinical trials of remdesivir after a batch of the drug arrived in the country, the state-run Xinhua news agency reported.

In their study, the researchers assessed remdesivir and chloroquine and five other drugs against a clinical isolate of 2019-nCoV in vitro. The five were: ribavirin, penciclovir, nitazoxanide, nafamostat, and favipiravir (T-705 or Avigan).

“Notably, Remdesivir (EC50 = 0.77 μM; CC50 > 100 μM; SI > 129.87) and chloroquine (EC50 = 1.13 μM; CC50 > 100 μM, SI > 88.50) potently blocked virus infection at low-micromolar concentration and showed high SI [selectivity index],” the researchers reported.

A time-of-addition assay showed remdesivir to function at a stage post virus entry, which according to the scientists appeared to reflect its putative anti-viral mechanism as a nucleotide analogue.

“Our data showed that EC90 value of remdesivir against 2019-nCoV in Vero E6 cells was 1.76 μM, suggesting its working concentration is likely to be achieved in NHP,” the researchers added. “Our preliminary data showed that remdesivir also inhibited virus infection efficiently in a human cell line (human liver cancer Huh-7 cells), which is sensitive to 2019-nCoV.”
Pursuing remdesivir patent

Remdesivir proved sufficient effective, the institutions added in a statement issued by the Wuhan Institute of Virology, that they have applied for Chinese invention patents on January 21 “in accordance with international practice and from the perspective of protecting national interests (Resistance to new coronaviruses in 2019).”

The institutions stated that they also plan to pursue multiple patents worldwide as allowed under the global Patent Cooperation Treaty.

However, the institutions added that should Gilead “intend to contribute to China’s epidemic prevention and control, we both agree that if the state needs it, we will not require the implementation of the rights claimed by the patent for the time being.”

The institutions have opted not to pursue patents for chloroquine, which is already marketed in China, also with the aim of encouraging partners to join them in efforts to prevent and control the spread of coronavirus.

Gilead said on January 31 that it will partner with officials to carry out clinical trials of remdesivir, and has offered the Nuc inhibitor for use in a “small number” of patients with 2019-nCoV for emergency treatment in the absence of any approved treatment options. The company added that it is also expediting “appropriate” laboratory testing of remdesivir against 2019-nCoV samples.

Gilead chief medical officer Merdad Parsey, MD, PhD, has cited positive in vitro and in vivo activity shown by remdesivir in animal models against MERS and SARS, coronaviruses that are structurally similar to 2019-nCoV.

Remdesivir also showed “no adverse events” after it was administered as a treatment to the first American confirmed to be infected with 2019-nCoV, according to “First Case of 2019 Novel Coronavirus in the United States,” a case study published Friday in The New England Journal of Medicine by members of the Washington State 2019-nCoV Case Investigation Team.
Rating unchanged despite potential

“This case-report suggests that remdesivir could be an effective treatment for 2019-nCoV and should be formally investigated as a therapeutic agent for the treatment of 2019-nCoV pneumonia, and we are encouraged by Gilead’s efforts to further investigate remdesivir, through the recently initiated trial in collaboration with Chinese health authorities,” SVB Leerink director of therapeutics research and senior research analyst, Geoffrey C. Porges, MBBS, wrote Monday in an investor note along with colleagues Neil Puri, MD, Ke (Andrew) Yuan, CFA, CPA, and Bradley Canino, CPA.

They added, however, that they would not change SVB Leerink’s “Market Perform” rating of Gilead stock as a result of remdesivir’s potential in treating coronavirus.

“From a societal perspective, we are unequivocally supportive of Gilead’s (and other company’s) efforts to develop an effective treatment for this rapidly spreading, and potentially fatal, infection; however these activities do not alter our fundamental assessment and outlook for GILD’s stock, as therapies of this nature are likely to provide a short-term financial boost, but unlikely to yield a significant impact on long-term shareholder value,” Porges and colleagues wrote.

Atazanavir, an antiretroviral medication used to treat and prevent HIV, was the most promising chemical compound to emerge from an artificial intelligence-based prediction model for antiviral drugs that may be effective on 2019-nCoV, according to an article posted Sunday on the bioRxiv preprint server by researchers at Deargen and Dankook University in South Korea, and Emory University in Atlanta—the latest report in GEN’s ongoing coverage of the 2019-nCoV novel coronavirus outbreak.

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发表于 2020-2-6 15:52 |显示全部帖子
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艾滋病毒,HCV / HIV(未定义),纳塔普
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冠状病毒:随着研究人员发表积极的体外研究结果,吉利德的Remdesivir开始试验
通过
亚历克斯·菲利皮迪斯
--
2020年2月5日

在中国研究人员建议将抗病毒药物候选药物雷姆昔韦在人体内评估为2019-nCoV的潜在治疗手段后的第二天,吉利德科学的雷姆昔韦在新的冠状病毒爆发的中心中国武汉开始了临床试验。

在中国研究人员建议将抗病毒药物瑞姆昔韦在人类中评估为2019-nCoV的潜在治疗手段的第二天后,吉利德科学公司的瑞姆昔韦就在新型冠状病毒爆发的中心中国武汉开始了临床试验。

中国国家药品监督管理局已经批准了中日友好医院和中国医学科学院的申请,以进行评估雷姆昔韦的试验。

今天,中国国有的新华社报道说,友谊医院计划在两项试验中共研究761名患者,其中一项试验评估308名轻度或中度感染,另一项评估453名重度感染患者。已正式启动的第三阶段研究。

科技部中国生物技术发展中心副主任在国家卫生委员会举行的新闻发布会上说:“我们希望这些试验能取得良好的结果。”

根据国家卫生委员会今天报告的最新冠状病毒数据,周二有65人死亡,另外3887人被确认感染。迄今为止,已确认24324人感染了2019-nCoV,死亡490人,比2002-03年SARS爆发时的349人死亡要多,有892名患者治愈并出院。

中国最近几天采取了许多控制疫情的举措,据新华社今天报道,习近平主席说:“感染的预防和控制处于关键时刻,并强调以法律为基础开展这项工作极为重要,以科学有序的方式进行,“在习近平领导的中共中央全面法治委员会第三次会议上。

习近平还表示,中国可能要求一些官员对遏制2019-nCoV的初步反应负责。他以前曾以“缺点和不足”为特征来形容中国的最初反应。
雷姆昔韦,氯喹“高效”

该试验宣布是在该实验药物和市售抗疟药氯喹显示出有希望的临床前结果的第二天开始的。

研究人员在“ Remdesivir和氯喹在体外有效抑制新近出现的新型冠状病毒(2019-nCoV)的研究中报道说:“我们的发现表明,remdesivir和氯喹在体外控制2019-nCoV感染方面非常有效。”致《自然》杂志《细胞研究》(Cell Research)编辑的信。

研究人员补充说:“由于这些化合物已经在具有安全记录的人类患者中使用,并显示出对多种疾病有效,因此我们建议应在患有新型冠状病毒疾病的人类患者中对它们进行评估。”

该研究小组由来自中国科学院武汉病毒研究所/国家生物安全中心和国家军事医学科学院急诊医学药物预防与控制研究所的研究人员组成。

据国营新华社报道,研究人员周二发表了他们的建议,就在同一天,中国科学技术部宣布将在一批药物到达该国后启动雷姆昔韦的人体临床试验。

在他们的研究中,研究人员在体外对remdesivir和chloroquine以及其他五种药物进行了针对临床分离的2019-nCoV的评估。这五个是:利巴韦林,喷昔洛韦,硝唑尼特,那法莫司和法维吡韦(T-705或阿维甘)。

“值得注意的是,伦德西韦(EC50 = 0.77μM; CC50> 100μM; SI> 129.87)和氯喹(EC50 = 1.13μM; CC50> 100μM,SI> 88.50)在低微摩尔浓度下有效地阻断了病毒感染,并显示出较高的SI [选择性指数],“研究人员报道。

加时分析表明瑞姆昔韦在病毒进入后的一个阶段起作用,据科学家们看来,这似乎反映了其作为核苷酸类似物的推定抗病毒机制。
研究人员补充说:“我们的数据显示,雷莫昔韦在Vero E6细胞中相对于2019-nCoV的EC90值为1.76μm,这表明它可能在NHP中达到其工作浓度。” “我们的初步数据显示,雷姆昔韦还可以有效抑制人细胞系(人肝癌Huh-7细胞)中的病毒感染,该细胞系对2019-nCoV敏感。”
取得remdesivir专利

武汉病毒学研究所在一份声明中补充说,Remdesivir足够有效,它们“根据国际惯例并从保护国家利益的角度出发,于1月21日申请了中国发明专利(对新冠状病毒的抵抗力2019)。”

这些机构表示,他们还计划在全球专利合作条约允许的范围内在世界范围内寻求多项专利。

但是,这些机构补充说,如果吉利德“打算为中国的流行病预防和控制做出贡献,我们都同意,如果国家需要它,我们暂时将不需要实施专利所要求的权利。”

这些机构选择不寻求已在中国销售的氯喹的专利,其目的还在于鼓励合作伙伴共同努力,以预防和控制冠状病毒的传播。

吉利德于1月31日表示,它将与官员合作进行瑞姆昔韦的临床试验,并在没有任何批准的治疗方案的情况下,将Nuc抑制剂提供给少数使用2019-nCoV的患者进行紧急治疗。该公司补充说,它还将加快针对2019-nCoV样品的瑞德昔韦的“适当”实验室测试。

吉利德首席医学官默达德·帕西(Merdad Parsey)博士引用了瑞德昔韦在抗MERS和SARS冠状病毒的动物模型中表现出的体外和体内阳性活性,这些冠状病毒的结构类似于2019-nCoV。

根据“ 2019年美国新型冠状病毒的第一例”报道,在对第一个被确认感染了2019-nCoV的美国人进行治疗后,雷姆昔韦还显示出“无不良事件”。华盛顿州2019-nCoV病例调查小组成员撰写的《新英格兰医学杂志》。
尽管有潜力,评级仍保持不变

“该病例报告表明,瑞德昔韦可能是2019-nCoV肺炎的有效治疗方法,应作为治疗2019-nCoV肺炎的治疗剂进行正式研究,并且吉利德公司通过最近的努力进一步研究了瑞德昔韦,这令我们感到鼓舞SVB Leerink治疗研究总监兼高级研究分析师Geoffrey C. Porges(MBBS)周一在一份投资者报告中与同事Neil Puri医学博士,CFA Ke(Andrew)Yuan一起在投资者报告中写道, CPA和Bradley Canino,CPA。

他们补充说,但是,由于瑞姆昔韦具有治疗冠状病毒的潜力,他们不会改变SVB Leerink对吉利德股票的“市场表现”评级。

“从社会角度来看,我们明确支持吉利德(及其他公司)为迅速传播这种可能致命的感染而开发有效治疗方法的努力;但是,这些活动不会改变我们对GILD股票的基本评估和前景,因为这种性质的疗法可能会在短期内推动财务增长,但不会对长期股东价值产生重大影响。” Porges及其同事写道。

根据本周日在bioRxiv预印本上发表的一篇文章,用于治疗和预防HIV的抗逆转录病毒药物Atazanavir是基于人工智能的抗病毒药物预测模型中最有前途的化合物,该预测模型可能对2019-nCoV有效这是GEN持续报道2019年nCoV新型冠状病毒爆发的最新报告,由韩国迪尔根大学,丹国大学和亚特兰大埃默里大学的研究人员提供。
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