请铭记并感谢这位雪中送炭的德国科学家:Rolf Hilgenfeld

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24 JANUARY 2020

This scientist hopes to test coronavirus drugs on animals in locked-down Wuhan
Structural biologist Rolf Hilgenfeld has been working on coronavirus treatments since the SARS outbreak.

David Cyranoski

  • Coronavirus particles.

    Coronaviruses take their name from their crown-like halo.Credit: EYE OF SCIENCE/SPL
Shanghai, China

As China battles to halt the spread of a new virus that has infected hundreds of people, one structural biologist is hoping to get to the epicentre of the outbreak, the locked-down city of Wuhan.

Rolf Hilgenfeld, who is based at the University of Lübeck in Germany, has been trying to develop a cure for coronaviruses since the 2002–03 outbreak of severe acute respiratory syndrome (SARS). Hilgenfeld is hoping to get into Wuhan in central China, to work with researchers there to test two compounds in animals infected with the new, related coronavirus, which emerged in the city late last year. The early-stage drug candidates are not ready for use in people, but Hilgenfeld wants to start animal testing with the aim of developing treatments for future coronavirus outbreaks.

Rolf Hilgenfeld mugshot.

Structural biologist Rolf Hilgenfeld.Credit: Rolf Hilgenfeld
Hilgenfeld, who is currently in China, tells Nature about his quest — and the obstacles.

Why are you visiting China?
I planned to go to China anyway, but after this virus emerged I contacted some collaborators in Wuhan. I have two compounds, and I would like to test them against the new virus, so I am seeking collaborators who have samples of the virus.

Many people would like to get out of Wuhan, but you’re trying to get in. Are you worried for your safety?
I had the same experience going to Beijing in 2003 for SARS. I was on a flight with eight people. I had to connect through Japan because there were no flights from Europe. In Wuhan, I will wear a face mask all the time.

At what stage of development are your compounds?
We have just been getting them ready to be tested in a mouse model of Middle East respiratory syndrome (MERS) with a collaborator in Germany. Those tests should start in the next two weeks. In cell culture, we know they work against SARS and MERS [which are both also caused by coronaviruses]. The compounds have been tested in mice; we know they are safe. But these are not drugs. They are not very advanced. They’ve never been tested in humans.

If all goes well, how fast could you finish the preclinical testing? Could the compounds help subdue the new virus?
The problem with these antiviral compounds is that when you have the compound ready there are no patients. The new coronavirus outbreak will probably be over in six months, like the SARS one was. After six months, we could have data that show one of our compounds works against the new virus, and would be able to collaborate on developing it as a drug. But if by then the outbreak is over, there will be no patients, so how can you do clinical trials?

And the total number of people infected, if you combine SARS, MERS and this new virus, is under 12,500 people. That’s not a market. The number of cases is too small. Pharmaceutical companies are not interested.

How can you develop drugs that target coronaviruses, then?
We have actually developed compounds that are active against both the coronaviruses and a large family of enteroviruses, which include human rhinoviruses [the main cause of common colds] and hand, foot and mouth disease. Every year, half a million children get one called enterovirus-71, so we would aim to go into clinical trials for these diseases. We can get pharma involved. Then if we have something approved for those, we can use the drug quickly next time there is a coronavirus outbreak.

How do the drugs work?
They are directed at viral proteases, which have common features in both coronaviruses and enteroviruses. We are structural biologists. We look at the crystal structure and then design something that targets both. It’s killing two birds with one stone, as you say in English, or killing two flies with one swatter, as we say in German.

Which compounds have you brought to China?
The ones I brought over are a second generation of compounds that we prepared for the mouse MERS experiments. There is a publication about them under review.

Does China already have an animal model you can use to test your compounds?
It’s not so easy to make a mouse model. The mouse doesn’t interact with the MERS or SARS viruses because of a difference in the ACE2 receptor [which the virus uses to enter cells]. You must first engineer a mouse that carries the human version of ACE2 and you must delete the mouse version.

What will you do if you cannot get to Wuhan?
If Wuhan airport doesn’t open by next week, I will send my compounds by courier.

Some people are under the impression that you’re delivering a cure for the disease. Does this concern you?
What happened is that a radio station contacted me because I do work related to SARS. I told them I was going to China and they wrote a story with a question mark in the title asking whether I could save people from the Wuhan virus. That was picked up. The idea that I have a drug is premature. I am trying to correct that.

 
武汉肺炎利好消息!首株病毒毒种成功分离,德教授正携最强抑制剂来华驰援
2020-01-25 00:07:12 创事记 微博 作者: 我有话说(3人参与)

原标题:武汉肺炎利好消息!首株病毒毒种成功分离,德教授正携最强抑制剂来华驰援 来源:量子位


量子位 报道 | 公众号 QbitAI

除夕之夜,传来了又一好消息。

中国疾控中心成功分离了我国首株新型冠状病毒毒种。

其信息及电镜照片、新型冠状病毒核酸检测引物和探针序列等均由国家病原微生物库权威发布,并提供共享服务。

fd56-innckcf5287714.jpg

链接:http://nmdc.cn/#/nCoV
而来自国际的驰援也已经在路上。

德国吕贝克大学的顶级研究员希尔根费尔德(Rolf Hilgenfeld)教授正乘飞机飞往中国。

他将带来的,是吕贝克大学研发的最强冠状病毒抑制剂。

4919-innckcf5287712.jpg

希尔根菲尔德是吕贝克大学生化研究所主任,主要研究领域为病毒学,是冠状病毒和流行性呼吸道疾病研究领域的专家。

2003年非典疫情期间,希尔根费尔德就曾奔赴北京,为抗击非典做出贡献。

他和其他四位科学家在Science上发表的论文,揭示了冠状病毒主要蛋白酶的3D模型,并提供了抗击SARS药物的基本设想。

希尔根费尔德解释说,武汉病毒中82%的结构和SARS病毒相同,而重要的蛋白酶则有96%和SARS病毒相同。

虽然其研究成果大部分是基于SARS病毒的,对于新型冠状病毒有无实际效果,尚没有确切研究证明。但希尔根费尔德带来的,是长久以来积累下的冠状病毒研究经验和成果,无疑是一个利好消息。

而另一方面,由钟南山院士任组长、14位专家组成的新型冠状病毒感染的肺炎疫情联防联控工作机制科研攻关专家组也在积极开展疫情应急科研攻关。

目前,“新型冠状病毒感染的肺炎疫情科技应对”第一批8个应急攻关项目已经紧急启动,经费拨付到位。

下一步,科技部将会同相关部门,全力做好应急攻关任务的组织协调,充分利用现有研发基础,集中力量,快速突破,强化防控诊疗技术研发和成果应用,为坚决遏制疫情蔓延势头提供科技支撑。

着重在病毒溯源、传播途径、动物模型建立、感染与致病机理、快速免疫学检测方法、基因组变异与进化、重症病人优化治疗方案、应急保护抗体研发、快速疫苗研发、中医药防治等10个方面进行部署。

面对疫情,科研人员正在不懈地努力着。

而作为普通人,我们除了致敬医护人员、科研人员,关注疫情发展,还是要主动防护,保护好自己,就是对社会最大的负责。

祝福每一位读者,过一个平安健康的新年。

最后,再次同步下各大关注渠道:
1、新浪新闻专题,会更新各家媒体的报道,速度快:
2、腾讯新闻实时病例数据统计表,有曲线图:
3、丁香园实时疫情地图,同时有最新快讯更新:
4、财新新闻专题:武汉肺炎防御全记录。有比较多专家采访,限时免费阅读:
AI内参|把握AI发展新机遇
 
为啥是“雪中送炭”?
 
强抑制剂不算药吗?

Some people are under the impression that you’re delivering a cure for the disease. Does this concern you?


What happened is that a radio station contacted me because I do work related to SARS. I told them I was going to China and they wrote a story with a question mark in the title asking whether I could save people from the Wuhan virus. That was picked up. The idea that I have a drug is premature. I am trying to correct that.
 
Some people are under the impression that you’re delivering a cure for the disease. Does this concern you?

What happened is that a radio station contacted me because I do work related to SARS. I told them I was going to China and they wrote a story with a question mark in the title asking whether I could save people from the Wuhan virus. That was picked up. The idea that I have a drug is premature. I am trying to correct that.
按照我的理解,他的药还需要进行动物实验,起码是一个很好的研究成果,他的努力已经取得了初步的成果。即使是premature,在这么短的时间内,能取得这样的效果和他2003年在中国帮助SARS的经历密切相关。他是为控制这个瘟疫带着重大希望的科学家。

在武汉封城的危险时刻,他却冒着巨大风险逆流而上,这不能称为雪中送炭吗?难道是凑热闹来了?
 
去掉雪中送碳,村长就没意见了 ;)
按照我的理解,他的药还需要进行动物实验,起码是一个很好的研究成果,他的努力已经取得了初步的成果。即使是premature,在这么短的时间内,能取得这样的效果和他2003年在中国帮助SARS的经历密切相关。他是为控制这个瘟疫带着重大希望的科学家。

在武汉封城的危险时刻,他却冒着巨大风险逆流而上,这不能称为雪中送炭吗?难道是凑热闹来了?
 
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