病毒源头 （转）
shearwater • • 15635 次浏览王立铭
现在能够确认的是，这次新冠病毒肺炎的幕后真凶就是一种刚刚发现的新型冠状病毒（2019-nCoV）。
这已经是21世纪以来，冠状病毒家族的成员第三次肆虐人类世界了。2003年和2012年，SARS病毒（严重急性呼吸综合征病毒）和MERS病毒（中东呼吸综合征病毒）曾经两次突然降临人类世界，在中国和中东地区留下了至今尚未痊愈的伤疤。
我得提醒一句，确认任何一种全新传染病的病原微生物都不是一件特别容易的事情。你可能直觉上觉得看看肺炎患者的肺部有什么微生物就可以了，但是问题是在大多数时候一个人身体里总是寄生着上千种不同的细菌和病毒等微生物，因此确定病原体的时候医生和科学家们也需要非常小心才行。你可能还记忆犹新的一个反例，就是2003年SARS流行时曾经有科学家（中国疾控中心首席研究员，中国工程院院士洪涛）错误地将患者体内的某种衣原体判断成了病原体，险些造成了疫情管理的大问题。
而如何判断一种传染病的病原体，其实有一个非常古老但行之有效的办法：科赫法则。
这是德国细菌学家科赫在1884年提出的标准，用来判断某种病原体和某个传染病之间的因果关系：
每一个病患体内都能找到大量的这种病原体；
这种病原体可以从患者体内被分离出来，然后在体外培养；
体外培养的病原体可以让健康人患病；
新患病的人体内仍然可以找到同样的病原体。
在此后的一百多年里，科赫法则也在持续地被修正过程中，但是总体而言仍然是整个科学界明确传染病病原体的金标准。
具体到这次新冠病毒肺炎，中国科学家们在最早发病的几十位患者体内，利用电子显微镜、RT-PCR和高通量DNA测序等方法检测到了这种病毒的存在（科赫法则1）[1,2]；也成功分离出了这种病毒颗粒并且证明了它们在培养皿里仍然能够侵染人上皮细胞（科赫法则2）[1]。当然，因为目前人们还没有新冠病毒的动物模型。无法直接验证科赫法则3和4，但是科学家们也证明了只要在老鼠细胞里转入一个人类的ACE2蛋白——猜测中的新冠病毒受体，病毒就可以顺利侵染这些老鼠细胞。这个结论至少是部分支持了科赫法则3和4的成立[3]。
换句话说，在当下这个时间点，中国科学家们已经尽全部可能地证明了新冠病毒就是这种全新肺炎的病原体。
那接下来的问题是，这种病原体从何而来？
首先要明确的是，虽然同属于冠状病毒家族，但新冠病毒并非SARS或者它的变种，两者之间的基因序列相似度只有80%，是相当遥远的亲戚（对比一下，人和猩猩的基因组相似度高达98%，人和人之间的相似度更是超过99.9%）。
人们已经获得了新冠病毒的完整基因组序列信息[4]，也有不少研究组已经把它和已知的许多冠状病毒序列加以比对。其中特别值得提出的是两种天然寄生于蝙蝠身体内的冠状病毒：一种存在于舟山地区的某种蝙蝠体内，序列相似度接近90%[1]；另一种则存在于云南菊头蝠体内，序列相似度高达96%[3]。
而我们已经知道，同属冠状病毒家族的SARS和MERS的天然宿主很可能都是蝙蝠。蝙蝠这类哺乳动物体温较高、免疫系统特殊，也是很多种危险病毒的天然宿主。从这个角度说，新冠病毒的天然宿主确实很可能也是蝙蝠。
但是我还是得提醒你注意：和确定一种传染病的病原体一样，确认病原体在自然界的天然宿主也一直是件非常困难的事情，要求我们了解病毒从天然宿主到人传播的全链条。这一点实际上SARS和MERS病毒都还没有彻底证明。
其实比确认天然宿主更重要的，是确认新冠病毒的中间宿主——也就是找到它从蝙蝠到人之间的中间链条。要知道，虽然新冠病毒和云南菊头蝠体内的病毒高度相似，但是4%的差别其实也意味着蝙蝠体内的病毒是不太可能直接传染人的。另外，新冠病毒肺炎患者体内的病毒样本彼此之间基因序列高度一致，这本身也提示病毒应该是在某种中间宿主体内完成进化之后开始爆发的[5]。
在SARS和MERS的案例里，科学家们确认果子狸和骆驼是两种病毒最重要的中间宿主[6,7]，病毒在它们的种群内广泛传播和变异，最终变成了可以直接入侵人体导致疾病的病毒。那么在新冠病毒的案例里，谁是可能的中间宿主呢？这个问题的回答对于我们日后防范新冠病毒卷土重来是至关重要的。
但是很遗憾的是，目前我们没有很好的猜测方向。因为早期病例大多和武汉市内的华南海鲜市场有关，因此一个主流的猜测是也许那里贩卖的某种野生动物是病毒的中间宿主。但是遗憾的是科学家们没有来得及在市场被封闭之前采集野生动物样本，因此只来得及在市场的环境中进行检测并确实发现了病毒[8]。在这里我可以给出一个粗糙的猜测：这种中间宿主应该是某种能够较大规模饲养的半野生状态的哺乳动物，这样才能为病毒的突变积累提供时间；竹鼠、果子狸等动物是可能的寻找方向。在未来，规范和严打野生动物贩卖肯定是非常重要的传染病管控措施。
所以简单总结一下，根据我们目前已知的信息，大概可以推测的病毒来源可能是这样的：
某种寄生于蝙蝠体内的冠状病毒因为某种原因进入了某种被人类大规模饲养的半野生哺乳动物体内；在那里，病毒通过广泛的互相传播和突变，获得了感染人类细胞并持续在人类个体之间传播的能力；在2019年年末的某个时间点，它传染进入了武汉一部分居民的体内并且导致了这场大规模的疾病爆发。
顺便说一句，根据这些讨论，你肯定能理解这种病毒大概率不是直接从野生蝙蝠传给人的，实际上也没有证据显示华南海鲜市场里贩卖蝙蝠，或者武汉居民对这种食物有特别的兴趣。
当然这个简单的推测还有不少问题无法回答。比如说，根据最新研究，新冠病毒肺炎最早的一位感染者本人其实并没有华南海鲜市场的接触经历，最早的几位患者当中也有不少人从来没有去过这个市场[2]，那么他们到底是如何被感染的？是病毒在一开始就具备了人和人之间高效传播的能力？还是说这种病毒另有传染源头？这些问题都仍然需要严肃的研究和回答。
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shearwater 楼主#1
与SADS差别王还有一篇新冠和SADS的差别分析，倒也是对P4 lab质疑的正面回应了。
https://tech.sina.com.cn/d/f/2020-01-29/doc-iihnzhha5213325.shtml -
#2
中东和伊波拉的源头至今还没有确认
当然武汉的新冠状病毒关键的中间载体也没有确认-但反应是算足够快的了 -
#3
再发一次，大家比较信洋人，还是病毒学家What is Wuhan Virus' pathophysiology?-Vipin Adlak,
The latest “novel coronavirus” emerged in Wuhan, China in mid-December and was quite rapidly preliminarily identified as likely a coronavirus, a common virus group which causes respiratory tract infections. This would be the third new coronavirus causing outbreaks in the past twenty years; it’s impressive seeing the scientific progress made since SARS (severe acute respiratory syndrome) in 2003.
SARS, the first widespread and deadly coronavirus, spread globally, infecting almost 8100 and killing 774 in 37 countries before it was brought under control. Cases began in November 2003, and exploded over the first three months. It took until July to stop the outbreak.
Scientists discovered the link to civets in live animal markets in China. Subsequently fruit bats were found to be the likely reservoir for the virus. At that time, China was initially reluctant to openly discuss the scope of the SARS problem. Other countries, as India and Peru, had experienced severe financial losses after epidemics were reported in their countries. Gro Harlem Brundtland, then Director general of WHO, helped gain the Chinese government’s cooperation. Greater transparency and sharing specimens and information was essential to stopping the epidemic, as were rigorous infection control precautions.
The next novel coronaviruses were human coronaviruses HKU-1 and NL63, then MERS, Middle East respiratory syndrome coronavirus, which emerged in 2012. A major problem in identifying and stopping that epidemic was that the Saudi government was less than forthcoming about the cases. In fact, there were solid reports that the Saudi government even directed physicians to misreport the cause of death of patients.
Human coronaviruses are common throughout the world. Seven different coronaviruses, that scientists know of, can infect people and make them sick. Some human coronaviruses were identified many years ago and some have been identified recently. Human coronaviruses commonly cause mild to moderate illness in people worldwide. Two newer human coronaviruses, MERS-CoV and SARS-CoV, have been known to frequently cause severe illness.
Symptoms
Common human coronaviruses
Common human coronaviruses, including types 229E, NL63, OC43, and HKU1, usually cause mild to moderate upper-respiratory tract illnesses, like the common cold. Most people get infected with these viruses at some point in their lives. These illnesses usually only last for a short amount of time.
Symptoms may include
runny nose
headache
cough
sore throat
fever
a general feeling of being unwell
Human coronaviruses can sometimes cause lower-respiratory tract illnesses, such as pneumonia or bronchitis. This is more common in people with cardiopulmonary disease, people with weakened immune systems, infants, and older adults.
Other human coronaviruses
Two other human coronaviruses, MERS-CoV and SARS-CoV have been known to frequently cause severe symptoms. MERS symptoms usually include fever, cough, and shortness of breath which often progress to pneumonia. About 3 or 4 out of every 10 patients reported with MERS have died. MERS cases continue to occur, primarily in the Arabian Peninsula. SARS symptoms often included fever, chills, and body aches which usually progressed to pneumonia. No human cases of SARS have been reported anywhere in the world since 2004.
Diagnosis
Your healthcare provider may order laboratory tests on respiratory specimens and serum (part of your blood) to detect human coronaviruses. Laboratory testing is more likely to be used if you have severe disease or are suspected of having MERS.
If you are experiencing symptoms, you should tell your healthcare provider about any recent travel or contact with animals. Most MERS-CoV infections have been reported from countries in the Arabian Peninsula. Therefore reporting a travel history or contact with camels or camel products is very important when trying to diagnose MERS.
Transmission
Human coronaviruses most commonly spread from an infected person to others through
the air by coughing and sneezing
close personal contact, such as touching or shaking hands
touching an object or surface with the virus on it, then touching your mouth, nose, or eyes before washing your hands rarely,
fecal contamination
In the United States, people usually get infected with common human coronaviruses in the fall and winter. However, you can get infected at any time of the year. Most people will get infected with one or more of the common human coronaviruses in their lifetime. Young children are most likely to get infected. However, people can have multiple infections in their lifetime.
Prevention
How to protect yourself There are currently no vaccines available to protect you against human coronavirus infection. You may be able to reduce your risk of infection by doing the following
wash your hands often with soap and water for at least 20 seconds
avoid touching your eyes, nose, or mouth with unwashed hands
avoid close contact with people who are sick
For information about hand washing, see CDC’s Clean Hands Save Lives!
How to protect others
If you have cold-like symptoms, you can help protect others by doing the following
See corona virus is still unknown for China like how it is spread , where does it come from ? ….and many more questions .
Actually this virus is found in animals or comes from animals according to Chinese scientists . And it may enter in our nostrils and infection lungs through air and eating meat or non veg.
Hence it's solution is not being found and trials are still to be done since it's new organism .
The only thing is that since many our Indians are living in China for different purpose so it may come enter in our country through them or through Chinese or others . So the thing we can do is follow some precautionary measure on our own level like cover our face with cotton cloth when visiting public place .
Do not eat meat , fish or eggs till the matter is solved . And do not eat outside . -
shearwater 楼主#4
关于疫苗和特效药王的叙述也很实在，拍胸口是没有用的
面对一种新型病毒导致的传染病，大家的第一反应肯定是，“有没有特效药”，“有没有疫苗”。希望能有好用的药物来帮助我们杀灭病毒，能有疫苗能帮我们快速形成免疫力，防止病毒的侵袭。 在新闻里确实能看到不少这方面的好消息，比如中科院上海药物所和上海科技大学的科学家们联手利用结构生物学辅助的化合物筛选平台，找到了三十种可能对新型冠状病毒有效的化合物[12]；再比如说中国疾病控制中心的研究人员已经启动了病毒疫苗的制备工作，疾控中心主任高福院士表态，“拍着胸口讲……疫苗是能开发出来的”[13]。类似的新闻还有不少，这里就不再列举了。 中国科学家的这些努力当然值得赞赏，但是很遗憾的是，针对一种全新的病毒和一场爆发式的传染病，特效药和疫苗都很难成为我们期待中的救星。 这背后的道理其实不难理解，药物开发也好，疫苗研制也好，从启动研究到真正量产，就算一切顺利，也仍然需要相当漫长的一段时间。而防控传染病爆发的时间窗口远没有那么长。说到底，远水不解近渴。 我们拿SARS做个例子，这种严重的呼吸道传染病2002年底在中国广东爆发，在2003年夏季逐渐被控制。但是SARS病毒的疫苗一直到2004年春季才启动人体试验，2006年才正式完成，而到那个时候SARS已经销声匿迹，没有大规模生产和接种疫苗的必要了[14]。药物开发就更是如此，至今人类也没有真的开发出针对SARS的特效药物，在实际治疗中仍然以支持治疗为主。所谓支持治疗，就是通过辅助呼吸、抗感染、补充体液等方法维持患者的生存，然后等待患者自身的免疫系统消灭入侵的病毒。实际上针对大多数病毒引起的传染病，人类都没有非常好的特效药物可以根除疾病。相关的例子还包括乙肝病毒引起的肝炎、流感病毒引起的流感、MERS和SARS病毒引起的呼吸道综合征等等。 17年前的SARS如此，面对刚刚突然爆发的新型冠状病毒肺炎，指望科学家们一夜之间拿出特效药和疫苗来也是不现实的，谁拍胸口都没有用，胸口拍烂都没有用。 当然，相比17年前的SARS，科学家对新型冠状病毒肺炎的研究和理解要快的多、深入的多，而曾经针对SARS的研究经验也提示了一些可能的方向。比如说上述中科院上海药物所和上海科技大学的联合研究就提示几种针对艾滋病毒的老药可能也对新型冠状病毒有效，实际上不幸在前线感染病毒的北大第一医院王广发主任，自己就尝试了一种名叫“洛匹那韦利托那韦”的艾滋病药物，似乎也确实显著缓解了病情[15]。这些线索当然有可能帮助我们找到能够辅助新冠肺炎的药物。还有，如今人类制备疫苗的速度也比十七年前有了很大的提高，甚至有研究机构计划在几个月内开展疫苗的临床试验（比如Moderna公司的RNA疫苗[16]。RNA疫苗理论上确实可以有更快的生产周期。但是这种可能性仅仅还停留在理论上，至今没有任何RNA疫苗已经完成人体临床研究）。 -
#5
强调
Human coronaviruses are common throughout the world. Seven different coronaviruses, that scientists know of, can infect people and make them sick.
Some human coronaviruses were identified many years ago and some have been identified recently. Human coronaviruses commonly cause mild to moderate illness in people worldwide.
Two newer human coronaviruses, MERS-CoV and SARS-CoV, have been known to frequently cause severe illness.
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shearwater 楼主#6
那印度哥们不是病毒学家吧Vipin Adlak - Drug Regulatory Affairs - BDR Pharmaceuticals ...
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#7
也许我记错Edward Moseley-这个才是？
还是其他的，最近看了一些virologist的东西
乱了