法国生物学家迪迪埃·拉乌尔特领导的团队应用氯喹治疗新冠病毒临床测试初见成效，24例临床测试显示，其中四分之三的患者治疗六日后病毒消失。
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氯喹和羟氯喹抗病毒机制的图解说明
来源: 吃与活 于 2020-03-23 09:49:03
川普总统推荐了氯喹治疗COVID-19，但有很多人质疑这是不是一种大力丸。其实，武汉病毒所很早就用实验表明氯喹在体外抑制新冠病毒的效力与瑞德西韦相仿。最近一篇文章总结了氯喹和羟氯喹的抗新冠病毒的作用机制(下图)。这些机制提示，氯喹和羟氯喹不仅阻断冠状病毒的侵袭和复制，而且降低了发生细胞因子风暴的可能性。中国（氯喹）和法国（羟氯喹）的临床试验表明氯喹和羟氯喹可以有效抗击COVID-19。因此，氯喹和羟氯喹虽然便宜，也非特效神药，但的确不是大力丸。
相比而言羟氯喹的副作用小，相对安全，是否羟氯喹的效果低于氯喹，还有待试验证明。两者长期大剂量使用都有安全问题，使用时一定要遵从医嘱。
下文及图来自文献(详见后)，供有疑问的朋友参考。
【1】二者均可干扰ACE2的糖基化，并降低宿主细胞上ACE2与冠状病毒表面上的棘突蛋白之间的结合效率。
【2】它们还可以提高内体和溶酶体的pH，从而防止病毒与宿主细胞融合以及随后的复制。
【3】羟氯喹进入抗原呈现细胞时，会阻止抗原加工和主要组织相容性复合体II类介导的自身抗原呈现给T细胞。随后抑制了T细胞的活化以及CD154和其他细胞因子的表达。
【4】羟氯喹破坏了DNA / RNA与TLR和核酸感受器环GMP合成酶(cGAS）的相互作用，因此激促炎基因的转录不能得到激发。
根据上述机制，氯喹和羟氯喹不仅阻断冠状病毒的侵袭和复制，而且降低发生细胞因子风暴的可能性。
Graphical illustration of the antiviral mechanisms of CQ and HCQ. Both chemicals can interfere with the glycosylation of ACE2 and reduce the binding efficiency between ACE2 on the host cells and the spike protein on the surface of the coronavirus. They can also increase the pH of endosomes and lysosomes, through which the fusion process of the virus with host cells and subsequent replication are prevented. When HCQ enters APCs, it prevents antigen processing and MHC class II-mediated autoantigen presentation to T cells. The subsequent activation of T cells and expression of CD154 and other cytokines are repressed. In addition, HCQ disrupts the interaction of DNA/RNA with TLRs and the nucleic acid sensor cGAS and therefore the transcription of pro-inflammatory genes cannot be stimulated. As a result, administration of CQ or HCQ not only blocks the invasion and replication of coronavirus, but also attenuates the possibility of cytokine storm. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.
参考文献：
Dan Zhou, Sheng-Ming Dai, Qiang Tong. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression.
Journal of Antimicrobial Chemotherapy, dkaa114, COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression
Published: 20 March 2020
COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression
来源: 吃与活 于 2020-03-23 09:49:03
川普总统推荐了氯喹治疗COVID-19，但有很多人质疑这是不是一种大力丸。其实，武汉病毒所很早就用实验表明氯喹在体外抑制新冠病毒的效力与瑞德西韦相仿。最近一篇文章总结了氯喹和羟氯喹的抗新冠病毒的作用机制(下图)。这些机制提示，氯喹和羟氯喹不仅阻断冠状病毒的侵袭和复制，而且降低了发生细胞因子风暴的可能性。中国（氯喹）和法国（羟氯喹）的临床试验表明氯喹和羟氯喹可以有效抗击COVID-19。因此，氯喹和羟氯喹虽然便宜，也非特效神药，但的确不是大力丸。
相比而言羟氯喹的副作用小，相对安全，是否羟氯喹的效果低于氯喹，还有待试验证明。两者长期大剂量使用都有安全问题，使用时一定要遵从医嘱。
下文及图来自文献(详见后)，供有疑问的朋友参考。
【1】二者均可干扰ACE2的糖基化，并降低宿主细胞上ACE2与冠状病毒表面上的棘突蛋白之间的结合效率。
【2】它们还可以提高内体和溶酶体的pH，从而防止病毒与宿主细胞融合以及随后的复制。
【3】羟氯喹进入抗原呈现细胞时，会阻止抗原加工和主要组织相容性复合体II类介导的自身抗原呈现给T细胞。随后抑制了T细胞的活化以及CD154和其他细胞因子的表达。
【4】羟氯喹破坏了DNA / RNA与TLR和核酸感受器环GMP合成酶(cGAS）的相互作用，因此激促炎基因的转录不能得到激发。
根据上述机制，氯喹和羟氯喹不仅阻断冠状病毒的侵袭和复制，而且降低发生细胞因子风暴的可能性。
Graphical illustration of the antiviral mechanisms of CQ and HCQ. Both chemicals can interfere with the glycosylation of ACE2 and reduce the binding efficiency between ACE2 on the host cells and the spike protein on the surface of the coronavirus. They can also increase the pH of endosomes and lysosomes, through which the fusion process of the virus with host cells and subsequent replication are prevented. When HCQ enters APCs, it prevents antigen processing and MHC class II-mediated autoantigen presentation to T cells. The subsequent activation of T cells and expression of CD154 and other cytokines are repressed. In addition, HCQ disrupts the interaction of DNA/RNA with TLRs and the nucleic acid sensor cGAS and therefore the transcription of pro-inflammatory genes cannot be stimulated. As a result, administration of CQ or HCQ not only blocks the invasion and replication of coronavirus, but also attenuates the possibility of cytokine storm. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.
参考文献：
Dan Zhou, Sheng-Ming Dai, Qiang Tong. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression.
Journal of Antimicrobial Chemotherapy, dkaa114, COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression
Published: 20 March 2020
COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression
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中国用氯喹但韩国用羟氯喹十锌，法国用羟氯喹十阿奇霉素。好像羟氯喹副作用比较小一点。
来源: lucy2008liu 于 2020-03-23 10:38:19
回答: 氯喹和羟氯喹抗病毒机制的图解说明 由 吃与活 于 2020-03-23 09:49:03
中国氯喹500mg/颗 一天两次 10天一个疗程。
韩国羟氯喹，这里报道都不一样，250mg 也有500毫克/天，10天一个疗程。锌量不清？
法国羟氯喹，首日剂量加大，然后逐渐400mg
来源: lucy2008liu 于 2020-03-23 10:38:19
回答: 氯喹和羟氯喹抗病毒机制的图解说明 由 吃与活 于 2020-03-23 09:49:03
中国氯喹500mg/颗 一天两次 10天一个疗程。
韩国羟氯喹，这里报道都不一样，250mg 也有500毫克/天，10天一个疗程。锌量不清？
法国羟氯喹，首日剂量加大，然后逐渐400mg
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1 min ago
Malaria drug will be one of the treatment options in coronavirus clinical trial, WHO officials say
From CNN's Minali Nigam and Jacqueline Howard
World Health Organization officials said that chloroquine, a drug typically used to treat malaria, will be one option included in a large, global clinical trial evaluating potential coronavirus treatment.
The FDA later tempered the President's remarks regarding chloroquine as an approved treatment, noting larger studies are needed to draw conclusions.
Currently there are no treatments — including chloroquine —that have proven safe and effective against Covid-19, WHO Director-General Tedros Adhanom Ghebreyesus said in a separate press briefing on Monday.
“There is a desperate need for effective therapeutics. There is currently no treatment that has been proven to be effective against Covid-19,” Tedros said on Monday.
WHO announced last week that it had organized the SOLIDARITY trial to examine potential treatment options for Covid-19 — chloroquine being one of them.
“We understand that this situation is very complex. Everybody, including President Trump, is trying to identify treatments that could help their people. And I think everybody is interested in further exploring the potential of chloroquine, so we are,” said Dr. Ana Maria Henao-Restrepo, a medical officer at WHO's Department of Immunization Vaccines and Biologicals.
Even without clinical evidence, some patients with Covid-19 are already taking chloroquine, but there could be harm in that too, Swaminathan said. Over the weekend, three people in Nigeria overdosed on the drug, which can cause seizures, nausea, vomiting, deafness, vision changes and low blood pressure.
“We have no knowledge that it’s going to benefit anyone,” Swaminathan said. “It is a really important point to focus our efforts on generating the evidence which could then be used to treat people properly and effectively.”
Malaria drug will be one of the treatment options in coronavirus clinical trial, WHO officials say
From CNN's Minali Nigam and Jacqueline Howard
World Health Organization officials said that chloroquine, a drug typically used to treat malaria, will be one option included in a large, global clinical trial evaluating potential coronavirus treatment.
This comes after the announcement President Trump made last week that the US Food and Drug Administration approved the “very powerful” drug chloroquine to treat coronavirus and that there were “very, very encouraging early results.”
The FDA later tempered the President's remarks regarding chloroquine as an approved treatment, noting larger studies are needed to draw conclusions.
Currently there are no treatments — including chloroquine —that have proven safe and effective against Covid-19, WHO Director-General Tedros Adhanom Ghebreyesus said in a separate press briefing on Monday.
“There is a desperate need for effective therapeutics. There is currently no treatment that has been proven to be effective against Covid-19,” Tedros said on Monday.
WHO announced last week that it had organized the SOLIDARITY trial to examine potential treatment options for Covid-19 — chloroquine being one of them.
“We understand that this situation is very complex. Everybody, including President Trump, is trying to identify treatments that could help their people. And I think everybody is interested in further exploring the potential of chloroquine, so we are,” said Dr. Ana Maria Henao-Restrepo, a medical officer at WHO's Department of Immunization Vaccines and Biologicals.
Even without clinical evidence, some patients with Covid-19 are already taking chloroquine, but there could be harm in that too, Swaminathan said. Over the weekend, three people in Nigeria overdosed on the drug, which can cause seizures, nausea, vomiting, deafness, vision changes and low blood pressure.
“We have no knowledge that it’s going to benefit anyone,” Swaminathan said. “It is a really important point to focus our efforts on generating the evidence which could then be used to treat people properly and effectively.”
迪迪埃·拉乌尔：声称氯喹是新冠肺炎克星的传染病专家何许人也
面对新冠肺炎大爆发的局面，全球各国的顶尖专家也都在寻求解药之际，法国传染病专家迪迪埃·拉乌尔（Didier Raoult）声称他使用抗击疟疾的药物氯喹让病人奇迹般康复，引起舆论轰动，也成为几天来医药界争论的焦点。
www.rfi.fr
法国卫生部长上周六表示，他已要求拉乌尔特教授的研究按照科学模式“由其他独立小组在其他医院大规模复制”。专家认为，相关临床实验结果有望在15天内出炉。
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怎么感觉世卫组织没有说真话似的鉴于上述原因，世衛组织在过往的新闻发布会上的态度一贯是：目前 “没有证据” 表明该药物可有效地治疗冠状病毒
麻省理工科技评论-发现改变世界的新兴科技
作为世界上最权威的科技商业媒体之一，MIT Technology Review于1899年在美国麻省理工学院创刊，至今已经走过121年，为全世界超过300万专业人士及商业领袖提供前瞻性的资讯和独到深入的行业趋势分析。www.mittrchina.com
实际上，自新冠疫情暴发以来，中国工程院院士钟南山曾数次提到过氯喹这种药物，不过他多次强调氯喹“并非特效药”。
在 2 月 18 日，在广东省举行的疫情防控新闻发布会上，钟南山说：“磷酸氯喹够不上特效药，但有治疗效果，副作用不大，值得研究和探讨。”次日，钟南山在会后接受中央广播电视总台的专访时称，氯喹现在不是特效药，但却是一个有效药，其最重要的优势在于安全。
3 月 17 日，法国马赛地中海传染病研究所主任迪迪埃 · 拉乌尔（Didier Raoult）领衔的研究中，研究人员使用了羟氯喹对 20 名新冠患者进行了治疗研究。另外 16 人为对照组，来自另一个临床现场。
该试验中，20 人每日接受 600 毫克羟氯喹治疗，终点评价指标是治疗第 6 天是否依然具有病毒载量。与对照组相比，治疗组病毒性治愈的比例明显增高。研究还发现，用羟氯喹和阿奇霉素联合治疗效果更好。
不过作者也承认，其研究局限性是病例太少，且有多名患者退出了测试。另有专家批评说，该研究没有对轻重症病人分组 / 分层，不是随机研究，且对照来自其他现场，这些都影响了试验结果的客观性。
中国的一项研究给出了不一样的结论。3 月 9 日，上海市公共卫生临床中心感染与免疫科卢洪洲等人在《浙江大学学报(医学版)》发表“硫酸羟氯喹治疗普通型 2019 冠状病毒病（COVID-19）患者初步研究”。结论是：以病毒转阴率、重症化率为主要终点的研究难以对药物的疗效进行比较。也就是说，硫酸羟氯喹治疗组并没有比对照组显示更好的疗效。硫酸羟氯喹较氯喹基础上增加了一个羟基基团，药效相当而毒性较低。
在治疗过程中，试验组 1 例患者发展为重症。入组后第 7 天，试验组中 13 例（86.7%）和对照组中 14 例（93.3%）咽拭子病毒核酸检测为阴性（P＞0.05）。在两周的访视期内，所有受试者的咽拭子核酸检测均转为阴性。
卢洪洲在接受 DeepTech 采访时表示，他们团队已经对研究作了调整，重新试验并投稿到英文期刊。在新的投稿论文中，将前 2 天的每天 400 毫克改为每天 800 毫克（一次 400 毫克，每日两次），之后为 400 毫克每天，疗程改为 10 天到 14 天，并且对 65 岁以下患者作了分层分析，发现治疗组排毒时间缩短，显示出了硫酸羟氯喹的疗效。
据介绍，调整方案的依据是，其一，前 2 天提高用药量可快速达到稳态有效浓度，显著缩短病原体清除时间，减少复发，降低耐药，且不良反应未见明显差异。其二，患者上呼吸道部位的病毒载量明显减少时，并不意味着肺泡内没有病毒，而硫酸羟氯喹给药需要很长的周期才能达有效稳态浓度。
卢洪洲认为，如需得出硫酸羟氯喹的疗效比对照组更优或更劣的结论，至少需要 784 例受试者。如果考虑受试者脱落、剔除等因素，病例数须达到近 900 例。这对于目前的临床研究来说是一个巨大的挑战。
他在论文中提示，在重症或危重症患者中评估硫酸羟氯喹可能更具可行性，比如是否可以降低病死率。另外，如果随着时间推移，受试者的病情确实逐渐减轻，则更提示开展随机对照临床研究的重要性。如果开展单臂研究，而以历史数据作为对照，则可能得到假阳性结果。
尽管氯喹在高剂量使用时可能具有毒性，但其普遍被认为是安全的，并且在中度剂量下耐受性良好。
罗氏制药总部（瑞士）医学总监刘挺在《中国银行保险报》撰文认为，磷酸氯喹在理论上是一个完美的抗新冠药物。
在新冠病毒感染初期，病毒在人体内大量复制，但临床症状可能表现为轻症，那么此时应当
减少病毒数量为主，支持机体免疫系统有效清除病毒，阻止病情向重症发展。一旦机体免疫系统被过度激活，释放大量炎症因子，造成了肺部组织损伤，临床症状就转成了重症，当情况进一步恶化出现呼吸和其他器官衰竭，这就是危重症了。对于重症病人，抑制病毒复制已经不是最主要治疗目标，而是控制过激的免疫系统，对症恢复器官功能。
刘挺认为，磷酸氯喹可以抑制多种病毒的感染和复制，体外实验显示可以在低浓度时抑制新冠病毒。另外它也可以治疗自身免疫疾病，调节免疫应答，抑制炎症反应。这样看来磷酸氯喹似乎是两种治疗机制的完美结合，在抑制免疫反应的同时也抑制病毒复制，避免了很多免疫抑制剂可能引起病毒复制的风险。
卢洪洲也表示，硫酸羟氯喹可以作为一个免疫抑制剂，可以抑制细胞因子风暴。
氯喹是处方药，它可能有副作用，并可能产生禁忌症。此前被发现的副作用就是“氯喹视网膜病”，当人体内累积了大量的氯喹之后将会导致永久性的视力丧失。但是，在总剂量低于 400 克（仅在治疗数年后才能达到剂量）的患者中，视网膜发生损害的情况是比较罕见的。
鉴于上述原因，世卫组织在过往的新闻发布会上的态度一贯是：目前 “没有证据” 表明该药物可有效地治疗冠状病毒。
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真也怪老川？自己吃药不小心搞错剂量了吧
Nigerians poisoned after taking doses of drug praised by Trump
Its safety and effectiveness is unproven for use against the coronaviruswww.theglobeandmail.com
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FDA已经同意纽约州从今日起可以采用羟氯喹和阿奇霉素治疗新冠重病患者
FDA green lights experimental drug trial in NYS
NEW YORK STATE (WSYR-TV) — Starting Tuesday, a trial drug will start being used to help fight COVID-19.
Governor Cuomo announced that New York has gotten approval from the FDA to treat seriously ill COVID-19 patients with hydroxy-chloroquine and zithromax. This treatment was published earlier this month in the Journal of Clinical Investigation, citing studies of it used in other viral diseases.
“It’s only a trial. It’s a trial for people who are in serious condition. But the New York State Department of Health has been working on this with some of New York’s best healthcare agencies and we think it shows promise,” Cuomo said.
Up to this date, there have been no published reports of this drug being used for coronavirus.
www.localsyr.com
FDA green lights experimental drug trial in NYS
NEW YORK STATE (WSYR-TV) — Starting Tuesday, a trial drug will start being used to help fight COVID-19.
Governor Cuomo announced that New York has gotten approval from the FDA to treat seriously ill COVID-19 patients with hydroxy-chloroquine and zithromax. This treatment was published earlier this month in the Journal of Clinical Investigation, citing studies of it used in other viral diseases.
“It’s only a trial. It’s a trial for people who are in serious condition. But the New York State Department of Health has been working on this with some of New York’s best healthcare agencies and we think it shows promise,” Cuomo said.
Up to this date, there have been no published reports of this drug being used for coronavirus.
FDA green lights experimental drug trial in NYS
NEW YORK STATE (WSYR-TV) — Starting Tuesday, a trial drug will start being used to help fight COVID-19. Governor Cuomo announced that New York has gotten approval from the FDA to treat …
www.localsyr.com
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钟南山再次提到氯喹：危害性不大，但对病毒的转阴率较为有效
来源：澎湃新闻作者：王俊
2020-03-18 20:49
3月18日，在广州市第46场疫情防控新闻通气会(广医一院专场)上，国家卫健委高级别专家组组长、中国工程院院士钟南山又一次提到老药氯喹。
钟南山表示，针对新型冠状病毒目前人类没有确切的有效治疗办法，但还是找到了一些方法，比如2004年已经开始在比利时试验的氯喹，这个老药还是很安全的。
“大概下周我们会有一个总结要发表。”钟南山说，氯喹危害性不大，但是对病毒的转阴率较为有效。
澎湃新闻记者注意到，新冠肺炎疫情以来，钟南山此前就曾多次提到氯喹。
2月18日，广东省举行新闻发布会通报疫情防控相关情况。钟南山院士表示，磷酸氯喹够不上特效药，但有治疗效果，副作用不大，值得研究和探讨。
随后，2月19日，广州呼吸健康研究院、美国哈佛大学、恒大集团三方联合成立的新型冠状病毒肺炎科研攻坚小组第二次视频会议在广州召开。会后，中央广播电视总台央视记者对钟南山进行了专访。
针对“像氯喹这样的老药新用跟研发一个新药相比，它的优势在哪里？”这一问题，钟南山表示，“我的看法，氯喹现在不是特效药，但是一个有效药。这优势是很大的。我们整个的中医就是这样，我们中医也是100多年、200多年的老药，你只要发现它有效果的话，就应该可以用它，因为最重要的优势在于它安全，有没有效可以很快的验证。周期是快很多，从实践到循证医学，就是从经验到循证医学，这是另外一条路。过去的研究新药都是从研发它的化学结构、改造，再离体实验，再动物实验，再到人的实验，要花很长时间。但是现在另外一条路是从经验然后到循证，然后到基础，这一条路也是同样重要。现在很多国家已经开始重视，像现在提的氯喹，有人问我是不是特效药，我想不能这么说，但是它是有效的。在面对一个从来没有遇见过的病的时候，我们要做一些实践，摸着石头过河，只要是它用了以后没有害处，那就可以尝试。”
钟南山再次提到氯喹：危害性不大，但对病毒的转阴率较为有效
在广州市第46场疫情防控新闻通气会（广医一院专场）上，国家卫健委高级别专家组组长、中国工程院院士钟南山又一次提到老药氯喹。
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