FlyTitle: The covid-19 virus

How SARS-COV-2 causes covid-19, and how it might be stopped

SARS-COV-2如何导致了2019冠状病毒病,以及如何可能阻止它

经济学人双语版-解剖杀手 Anatomy of a killer

THE INTERCONNECTEDNESS of the modern world has been a boon for SARS-CoV-2. Without planes, trains and automobiles the virus would never have got this far, this fast. Just a few months ago it took its first steps into a human host somewhere in or around Wuhan, in the Chinese province of Hubei. As of last week it had caused over 120,000 diagnosed cases of covid-19, from Tromsø to Buenos Aires, Alberta to Auckland, with most infections continuing to go undiagnosed.

现代世界的互联互通对于SARS-CoV-2(严重急性呼吸综合征冠状病毒2)来说是个福音。没有飞机、火车和汽车,病毒绝对无法这么快传播到眼下这个地步。就在几个月前,它迈出了第一步,感染了中国湖北省武汉市或附近的一位人类宿主。截至上周,从挪威的特罗姆瑟到阿根廷的布宜诺斯艾利斯,从加拿大的艾伯塔到新西兰的奥克兰,它已造成了超过12万2019冠状病毒病(covid-19)确诊病例,而大多数感染者仍未得到诊断。

But interconnectedness may be its downfall, too. Scientists around the world are focusing their attention on its genome and the 27 proteins that it is known to produce, seeking to deepen their understanding and find ways to stop it in its tracks. The resulting plethora of activity has resulted in the posting of over 300 papers on MedRXiv, a repository for medical-research work that has not yet been formally peer-reviewed and published, since February 1st, and the depositing of hundreds of genome sequences in public databases.

但互联互通也可能是它最终衰亡的原因。世界各地的科学家都将注意力集中在它的基因组和已知产生的27种蛋白质上,试图加深理解并找到阻止其继续扩散的方法。由此展开的大量研究活动自2月1日以来已经在MedRXiv(尚未经过正式同行评审和发表的医学研究论文库)上发表了300多篇论文,在公共数据库中存储了数百个基因组序列。

The assault on the vaccine is not just taking place in the lab. As of February 28th China’s Clinical Trial Registry listed 105 trials of drugs and vaccines intended to combat SARS-CoV-2 either already recruiting patients or proposing to do so. As of March 11th its American equivalent, the National Library of Medicine, listed 84. This might seem premature, considering how recently the virus became known to science; is not drug development notoriously slow? But the reasonably well-understood basic biology of the virus makes it possible to work out which existing drugs have some chance of success, and that provides the basis for at least a little hope.

对疫苗的攻关不仅发生在实验室。截至2月28日,中国临床试验注册中心列出了105项针对SARS-CoV-2的药物和疫苗试验,这些试验要么已经在招募患者,要么提出了招募计划。截至3月11日,美国的同类机构国家医学图书馆(National Library of Medicine)列出了84项试验。考虑到这种病毒最近才被科学界所知,这似乎有点仓促。药物研发不是非常缓慢的吗?但是,人们对这种病毒的基本生物学特性已经有了相当的了解,所以有可能确定哪些现有药物有一定的成功机会,这至少给了人们一点抱有希望的理由。

Even if a drug were only able to reduce mortality or sickness by a modest amount, it could make a great difference to the course of the disease. As Wuhan learned, and parts of Italy are now learning, treating the severely ill in numbers for which no hospitals were designed puts an unbearable burden on health systems. As Jeremy Farrar, the director of the Wellcome Trust, which funds research, puts it: “If you had a drug which reduced your time in hospital from 20 days to 15 days, that’s huge.”

哪怕一种药物只能稍稍降低死亡率或疾病的严重程度,也可能对疾病的进程产生很大的影响。武汉已经经历过而意大利部分地区正在经历的教训告诉我们,治疗远超出医院设计容量的大量重症患者会给卫生系统带来难以承受的负担。正如资助研究的惠康基金会(Wellcome Trust)总监杰里米·法拉(Jeremy Farrar)所说:“如果有一种药能把住院时间从20天缩短到15天,就会有巨大的作用。”

Little noticed by doctors, let alone the public, until the outbreak of SARS (severe acute respiratory syndrome) that began in Guangdong in 2002, the coronavirus family was first recognised by science in the 1960s. Its members got their name because, under the early electron microscopes of the period, their shape seemed reminiscent of a monarch’s crown. (It is actually, modern methods show, more like that of an old-fashioned naval mine.) There are now more than 40 recognised members of the family, infecting a range of mammals and birds, including blackbirds, bats and cats. Veterinary virologists know them well because of the diseases they cause in pigs, cattle and poultry.

直到2002年在广东省爆发SARS(严重急性呼吸道综合征)之前,很少有医生注意到冠状病毒,更不用说公众了。科学界在1960年代首次认识到了冠状病毒家族。之所以叫它们冠状病毒,是因为在那个时期的早期电子显微镜下,它们的形状让人想起了君主的王冠。(实际上用现代的观察方式看它们更像老式水雷。)这个家族现在有40多个已确认的成员,感染了许多哺乳动物和鸟类,包括黑鸫、蝙蝠和猫。兽医病毒学家非常了解它们,因为它们让猪、牛和家禽生病。

Virologists who concentrate on human disease used to pay less attention. Although two long-established coronaviruses cause between 15% and 30% of the symptoms referred to as “the common cold”, they did not cause serious diseases in people. Then, in 2002, the virus now known as SARS-CoV jumped from a horseshoe bat to a person (possibly by way of some intermediary). The subsequent outbreak went on to kill almost 800 people around the world.

专注于人类疾病的病毒学家过去很少关注它们。尽管两种历史悠久的冠状病毒带来了15%至30%所谓“普通感冒”的症状,但它们没有在人类中引发严重的疾病。然后在2002年,现在称为SARS冠状病毒(SARS-CoV)的病毒从中华菊头蝠传播到了人身上(可能是通过某种中间宿主),随后的疫病爆发导致全世界约800人死亡。

Some of the studies which followed that outbreak highlighted the fact that related coronaviruses could easily follow SARS-CoV across the species barrier into humans. Unfortunately, this risk did not lead to the development of specific drugs aimed at such viruses. When SARS-CoV-2—similarly named because of its very similar genome—duly arrived, there were no dedicated anti-coronavirus drugs around to meet it.

那次疫情爆发后的一些研究凸显了一个事实:相关冠状病毒可以很容易地追随SARS冠状病毒的脚步,跨越物种屏障感染人类。不幸的是,这种风险并没有让人们着手开发针对此类病毒的特殊药物。当SARS-CoV-2(因其基因组与SARS冠状病毒非常相似而得名)如约而至时,人们手边并没有专门的抗冠状病毒药物来抵御它。

As a known enemy

宿敌

A SARS-CoV-2 virus particle, known technically as a virion, is about 90 nanometres (billionths of a metre) across—around a millionth the volume of the sort of cells it infects in the human lung. It contains four different proteins and a strand of RNA—a molecule which, like DNA, can store genetic information as a sequence of chemical letters called nucleotides. In this case, that information includes how to make all the other proteins that the virus needs in order to make copies of itself, but which it does not carry along from cell to cell.

SARS-CoV-2病毒颗粒——专业上称为“病毒体”——直径约90纳米,大约相当于它感染的人类肺部细胞的百万分之一大。它包含四种不同的蛋白质和一条RNA链。RNA这种分子与DNA一样,可将遗传信息存储为由叫做核苷酸的化学字母组成的序列。在SARS-CoV-2病毒体中,该信息包括如何制造病毒要完成自我复制所需的、但并不在细胞间携带的所有其他蛋白质。

The outer proteins sit athwart a membrane provided by the cell in which the virion was created. This membrane, made of lipids, breaks up when it encounters soap and water, which is why hand-washing is such a valuable barrier to infection.

外层的蛋白质横贯了一层由产生病毒体的细胞提供的膜。这层由脂质制成的膜在遇到肥皂和水时会破裂,这就是为什么洗手是如此重要的防感染屏障。

The most prominent protein, the one which gives the virions their crown- or mine-like appearance by standing proud of the membrane, is called spike. Two other proteins, envelope protein and membrane protein, sit in the membrane between these spikes, providing structural integrity. Inside the membrane a fourth protein, nucleocapsid, acts as a scaffold around which the virus wraps the 29,900 nucleotides of RNA which make up its genome.

最醒目的蛋白质称为“刺突”,它突出在膜外,使病毒体具有冠状或水雷状的外观。另外两种蛋白,包膜蛋白和膜蛋白,位于刺突之间的膜中,支撑着结构完整性。在膜内,第四种蛋白(核衣壳)充当支架,病毒围绕该支架把构成其基因组的29,900个RNA核苷酸缠绕在一起。

Though they store their genes in DNA, living cells use RNA for a range of other activities, such as taking the instructions written in the cell’s genome to the machinery which turns those instructions into proteins. Various sorts of virus, though, store their genes on RNA. Viruses like HIV, which causes AIDS, make DNA copies of their RNA genome once they get into a cell. This allows them to get into the nucleus and stay around for years. Coronaviruses take a simpler approach. Their RNA is formatted to look like the messenger RNA which tells cells what proteins to make. As soon as that RNA gets into the cell, flummoxed protein-making machinery starts reading the viral genes and making the proteins they describe.

尽管活细胞将基因存储在DNA中,但仍会使用RNA进行其他一系列活动,例如将写在细胞基因组中的指令带至将指令转化为蛋白质的机器中。但是,各种各样的病毒却将其基因存储在RNA上。诸如导致艾滋病的HIV等病毒一旦进入细胞,就会产生其RNA基因组的DNA副本。这使它们能够进入细胞核并留在那里多年。冠状病毒的做法更简单。它们的RNA被排列成看起来像信使RNA,而信使RNA会告诉细胞要制造什么蛋白质。一旦这种RNA进入细胞,被蒙蔽的蛋白质制造机器就开始读取病毒基因并制造它们描述的蛋白质。

First contact between a virion and a cell is made by the spike protein. There is a region on this protein that fits hand-in-glove with ACE2, a protein found on the surface of some human cells, particularly those in the respiratory tract.

病毒体与细胞之间的首次接触是由刺突蛋白完成的。这种蛋白质上有一个区域可以紧密结合ACE2,一种在某些人体细胞(尤其是呼吸道细胞)表面发现的蛋白质。

ACE2 has a role in controlling blood pressure, and preliminary data from a hospital in Wuhan suggest that high blood pressure increases the risks of someone who has contracted the illness dying of it (so do diabetes and heart disease). Whether this has anything to do with the fact that the virus’s entry point is linked to blood-pressure regulation remains to be seen.

ACE2在控制血压方面发挥作用。而武汉市一家医院的初步数据表明,高血压会增加感染者的死亡风险(糖尿病和心脏病也是如此)。病毒的进入点与血压调节相关这一事实是否促成了这种风险,还有待观察。

Once a virion has attached itself to an ACE2 molecule, it bends a second protein on the exterior of the cell to its will. This is TMPRSS2, a protease. Proteases exist to cleave other proteins asunder, and the virus depends on TMPRSS2 obligingly cutting open the spike protein, exposing a stump called a fusion peptide. This lets the virion into the cell, where it is soon able to open up and release its RNA (see diagram below).

病毒体将自身附着在ACE2分子上后,就会让细胞表面的另一个蛋白质俯首听命。这就是蛋白酶TMPRSS2。蛋白酶的存在就是为了裂解其他蛋白质,而该病毒让TMPRSS2乖乖切开刺突蛋白,从而暴露出称为融合肽的残端。这使病毒体进入细胞,之后它很快就能打开并释放其RNA(参见下图)。

经济学人双语版-解剖杀手 Anatomy of a killer

Coronaviruses have genomes bigger than those seen in any other RNA viruses—about three times longer than HIV’s, twice as long as the influenza virus’s, and half as long again as the Ebola virus’s. At one end are the genes for the four structural proteins and eight genes for small “accessory” proteins that seem to inhibit the host’s defences (see diagram below). Together these account for just a third of the genome. The rest is the province of a complex gene called replicase. Cells have no interest in making RNA copies of RNA molecules, and so they have no machinery for the task that the virus can hijack. This means the virus has to bring the genes with which to make its own. The replicase gene creates two big “polyproteins” that cut themselves up into 15, or just possibly 16, short “non-structural proteins” (NSPs). These make up the machinery for copying and proofreading the genome—though some of them may have other roles, too.

冠状病毒的基因组比任何其他RNA病毒的都要大——是HIV的约四倍,流感病毒的两倍,埃博拉病毒的1.5倍。它的一端是四个结构蛋白的基因,以及似乎抑制了宿主防御能力的八个小“附件”蛋白的基因(见下图)。这些加在一起仅占了基因组的三分之一,其余都是一种称为“复制酶”的复杂基因的地盘。细胞对复制RNA分子并不感兴趣,所以它们没有用于这项任务的机器可供病毒劫持。这意味着病毒必须自己携带基因来完成复制。复制酶基因会生成两个大的“多蛋白”,它们将自身切成15个(或可能16个)短的“非结构蛋白”(NSP)。这些非结构蛋白构成了复制和校对基因组的机器,尽管其中一些可能还有其他作用。

经济学人双语版-解剖杀手 Anatomy of a killer

Once the cell is making both structural proteins and RNA, it is time to start churning out new virions. Some of the RNA molecules get wrapped up with copies of the nucleocapsid proteins. They are then provided with bits of membrane which are rich in the three outer proteins. The envelope and membrane proteins play a large role in this assembly process, which takes place in a cellular workshop called the Golgi apparatus. A cell may make between 100 and 1,000 virions in this way, according to Stanley Perlman of the University of Iowa. Most of them are capable of taking over a new cell—either nearby or in another body—and starting the process off again.

一旦细胞同时产生结构蛋白和RNA,就该开始生产新的病毒体了。一些RNA分子被核衣壳蛋白的副本包裹着,然后获得富含三种外层蛋白质的膜碎片。包膜蛋白和膜蛋白在这个组装过程中起着重要作用,该过程发生在称为“高尔基体”的细胞车间里。爱荷华大学的斯坦利·珀尔曼(Stanley Perlman)说,一个细胞可以这种方式制造100到1000个病毒体。它们中的大多数都可以占领一个新细胞,无论是在附近或是另一个身体内,再次开始这个过程。

Not all the RNA that has been created ends up packed into virions; leftovers escape into wider circulation. The coronavirus tests now in use pick up and amplify SARS-CoV-2-specific RNA sequences found in the sputum of infected patients.

并非所有产生的RNA最终都被包装到病毒体里,剩余的那些会散逸到更大范围的循环中。现在使用的冠状病毒检测可拾取并扩增在感染者的痰液中发现的SARS-CoV-2特异性RNA序列。

Take your time, hurry up

慢慢来,快一点

Because a viral genome has no room for free riders, it is a fair bet that all of the proteins that SARS-CoV-2 makes when it gets into a cell are of vital importance. That makes each of them a potential target for drug designers. In the grip of a pandemic, though, the emphasis is on the targets that might be hit by drugs already at hand.

由于病毒基因组并没有空间留给“闲人”,因此可以比较可靠地猜想SARS-CoV-2进入细胞后制造的所有蛋白质都至关重要。这使得每一种蛋白质都成为了药物设计者的潜在标靶。但是,面临全球疫病大流行的紧迫现实,当前的重点是那些可能被现有药物击中的标靶。

The obvious target is the replicase system. Because uninfected cells do not make RNA copies of RNA molecules, drugs which mess that process up can be lethal to the virus while not necessarily interfering with the normal functioning of the body. Similar thinking led to the first generation of anti-HIV drugs, which targeted the process that the virus uses to transcribe its RNA genome into DNA—another thing that healthy cells just do not do.

显而易见的标靶是复制酶系统。鉴于未被感染的细胞不会产生RNA分子的RNA副本,扰乱这种复制过程的药物就有可能杀死病毒,而不一定会干扰人体的正常运作。类似的思路催生了第一代抗HIV药物,它们瞄准艾滋病毒将自身RNA基因组转录为DNA的过程——这又是一件在健康细胞中不会发生的事。

Like those first HIV drugs, some of the most promising SARS-CoV-2 treatments are molecules known as “nucleotide analogues”. They look like the letters of which RNA or DNA sequences are made up; but when a virus tries to use them for that purpose they mess things up in various ways.

和最早的抗HIV药物一样,一些最有希望抗击SARS-CoV-2的疗法是被称为“核苷酸类似物”的分子。它们看起来就像是组成RNA或DNA序列的字母,但当病毒试图把它们用做组成序列的原料时,它们会以各种方式“捣乱”。

The nucleotide-analogue drug that has gained the most attention for fighting SARS-CoV-2 is remdesivir. It was originally developed by Gilead Sciences, an American biotechnology firm, for use against Ebola fever. That work got as far as indicating that the drug was safe in humans, but because antibody therapy proved a better way of treating Ebola, remdesivir was put to one side. Laboratory tests, though, showed that it worked against a range of other RNA-based viruses, including SARS-CoV, and the same tests now show that it can block the replication of SARS-CoV-2, too.

最受关注的抗SARS-CoV-2核苷酸类似物药物是瑞德西韦(remdesivir)。它最初由美国生物技术公司吉利德科学(Gilead Sciences)研发用于治疗埃博拉热病。当时这项工作已经进行到了表明该药对人类是安全的阶段,但因为抗体疗法被证实能更好地治疗埃博拉,瑞德西韦被暂放一边。但是,实验室测试表明,它可以对抗多种其他基于RNA的病毒,包括SARS冠状病毒,而现在相同的测试表明它也可以抑制SARS-CoV-2的复制。

There are now various trials of remdesivir’s efficacy in covid-19 patients. Gilead is organising two in Asia that will, together, involve 1,000 infected people. They are expected to yield results in mid- to late-April. Other nucleotide analogues are also under investigation. When they screened seven drugs approved for other purposes for evidence of activity against SARS-CoV-2, a group of researchers at the State Key Laboratory of Virology in Wuhan saw some potential in ribavirin, an antiviral drug used in the treatment of, among other things, hepatitis C, that is already on the list of essential medicines promulgated by the World Health Organisation (WHO).

目前有多个试验正在测试瑞德西韦对2019冠状病毒病患者的疗效。吉利德在亚洲组织了两个测试,共有1000名受感染者参与,预计将于4月中下旬出结果。其他核苷酸类似物药物也在检测中。位于武汉的病毒学国家重点实验室的一批研究人员筛查了七种已被批准用于其他用途的药物对SARS-CoV-2的效力,认为利巴韦林(ribavirin)具有一定潜力。这种抗病毒药物已被用于治疗丙型肝炎等疾病,列在世卫组织颁布的基本药物清单中。

Nucleotide analogues are not the only antiviral drugs. The second generation of anti-HIV drugs were the “protease inhibitors” which, used along with the original nucleotide analogues, revolutionised the treatment of the disease. They targeted an enzyme with which HIV cuts big proteins into smaller ones, rather as one of SARS-CoV-2’s NSPs cuts its big polyproteins into more little NSPs. Though the two viral enzymes do a similar job, they are not remotely related—HIV and SARS-CoV-2 have about as much in common as a human and a satsuma. Nevertheless, when Kaletra, a mixture of two protease inhibitors, ritonavir and lopinavir, was tried in SARS patients in 2003 it seemed to offer some benefit.

核苷酸类似物不是唯一的抗病毒药。第二代抗HIV药物是“蛋白酶抑制剂”,它们与最初的核苷酸类似物合并使用,彻底改变了艾滋病疗法。它们瞄准的是HIV病毒用于把大蛋白切割成小蛋白的一种酶,有点像SARS-CoV-2的其中一种非结构蛋白把自己大个的多蛋白切成了更多个小的非结构蛋白。尽管这两种病毒酶的作用相似,它们却毫不相干——HIV和SARS-CoV-2的共同点就如同人和一只蜜柑。但是,2003年在SARS患者中尝试使用两种蛋白酶抑制剂利托那韦(ritonavir)和洛匹那韦(lopinavir)的混合物克力芝(Kaletra)时,它似乎发挥了一些用处。

Another drug which was developed to deal with other RNA-based viruses—in particular, influenza—is Favipiravir (favilavir). It appears to interfere with one of the NSPs involved in making new RNA. But existing drugs that might have an effect on SARS-CoV-2 are not limited to those originally designed as antivirals. Chloroquine, a drug mostly used against malaria, was shown in the 2000s to have some effect on SARS-CoV; in cell-culture studies it both reduces the virus’s ability to get into cells and its ability to reproduce once inside them, possibly by altering the acidity of the Golgi apparatus. Camostat mesylate, which is used in cancer treatment, blocks the action of proteases similar to TMPRSS2, the protein in the cell membrane that activates the spike protein.

另一种被开发用于治疗其他RNA病毒(尤其是流感病毒)的药物是法匹拉韦(Favipiravir或favilavir)。它似乎干扰了生成新RNA的过程中涉及的一种非结构蛋白。但是,可能对SARS-CoV-2有效的现有药物并不限于最初设计用来抗病毒的那些。主要用于控制疟疾的药物氯喹(Chloroquine)在2000年代显示出对SARS冠状病毒有一定作用。在细胞培养研究中,它既降低了这种病毒入侵细胞的能力,也降低了病毒在入侵细胞后的繁殖能力,而这可能是通过改变高尔基体的酸性实现的。癌症药物甲磺酸卡莫司他(Camostat mesylate)可以阻断与细胞膜中激活刺突蛋白的TMPRSS2类似的蛋白酶的活动。

Not all drugs need to target the virus. Some could work by helping the immune system. Interferons promote a widespread antiviral reaction in infected cells which includes shutting down protein production and switching on RNA-destroying enzymes, both of which stop viral replication. Studies on the original SARS virus suggested that interferons might be a useful tool for stopping its progress, probably best used in conjunction with other drugs

并非所有药物都需要瞄准病毒本身。有些可以通过辅助免疫系统来发挥作用。干扰素促进了受感染细胞中广泛的抗病毒反应,包括关闭蛋白质生产和激活能破坏RNA的酶——两者均阻断了病毒复制。对SARS病毒的研究表明,干扰素可能是阻止该病毒进程的有用工具,与其他药物合并使用可能效果最佳。

Conversely, parts of the immune system are too active in covid-19. The virus kills not by destroying cells until none are left, but by overstimulating the immune system’s inflammatory response. Part of that response is mediated by a molecule called interleukin-6—one of a number of immune-system modulators that biotechnology has targeted because of their roles in autoimmune disease.

与之相反的是,在2019冠状病毒病中,免疫系统的某些部分被过度激活。该病毒并非通过把全部细胞破坏殆尽来夺命,而是通过过度激活了免疫系统的炎症反应。这种反应的一部分是由名为白介素6(interleukin-6)的分子介导的。生物技术已经根据一些免疫系统调节剂在自体免疫性疾病中扮演的角色将其列为标靶,白介素6是其中之一。

Actemra (tocilizumab) is an antibody that targets the interleukin-6 receptors on cell surfaces, gumming them up so that the interleukin-6 can no longer get to them. It was developed for use in rheumatoid arthritis. China has just approved it for use against covid-19. There are anecdotal reports of it being associated with clinical improvements in Italy.

雅美罗(Actemra,托珠单抗)是一种瞄准位于细胞表面的白介素6受体的抗体。它使这些受体粘合在一起,这样白介素6就无法再与之接触。它最初被研发用于治疗风湿性关节炎。中国刚刚批准将其用于治疗2019冠状病毒病。有传闻称意大利临床治疗出现改善与之有关。

While many trials are under way in China, the decline in the case rate there means that setting up new trials is now difficult. In Italy, where the epidemic is raging, organising trials is a luxury the health system cannot afford. So scientists are dashing to set up protocols for further clinical trials in countries expecting a rush of new cases. Dr Farrar said on March 9th that Britain must have its trials programme agreed within the week.

尽管中国正在开展许多试验,但那里的发病率下跌意味着现在已经很难再启动新试验。在疫病肆虐的意大利,组织试验是其医疗系统无法承受的奢侈。因此,科学家们正加紧制定方案,以在预期新增病例将激增的国家开展更多临床试验。法拉博士3月9日表示,英国必须在一周内商定其试验项目。

经济学人双语版-解剖杀手 Anatomy of a killer

International trials are also a high priority. Soumya Swaminathan, chief scientist at the WHO, says that it is trying to finalise a “master protocol” for trials to which many countries could contribute. By pooling patients from around the world, using standardised criteria such as whom to include and how to measure outcomes, it should be possible to create trials of thousands of patients. Working on such a large scale makes it possible to pick up small, but still significant, benefits. Some treatments, for example, might help younger patients but not older ones; since younger patients are less common, such an effect could easily be missed in a small trial.

国际试验也是高优先级事项。世卫组织首席科学家苏米娅·斯瓦米纳坦(Soumya Swaminathan)表示,为开展许多国家都可参与的试验,世卫正在努力敲定一项“主方案”。如果能把世界各地的患者汇聚起来并设定标准,如招募哪些受试者以及如何衡量结果等,应该就可以创建覆盖成千上万患者的试验。如此大规模的试验有可能取得虽小却仍重要的益处。例如,有些治疗可能对较年轻而非年长的患者有用。由于年轻患者在临床中更少见,因此在小规模试验中很容易错过这类疗效。

Come as you are

保持本色

The caseload of the pandemic is hard to predict, and it might be that even a useful drug is not suitable in all cases. But there are already concerns that, should one of the promising drugs prove to be useful, supplies will not be adequate. To address these, the WHO has had discussions with manufacturers about whether they would be able to produce drugs in large enough quantities. Generic drug makers have assured the organisation that they can scale up to millions of doses of ritonavir and lopinavir while still supplying the HIV-positive patients who rely on the drugs. Gilead, meanwhile, has enough remdesivir to support clinical trials and, thus far, compassionate use. The firm says it is working to make more available “as rapidly as possible”, even in the absence of evidence that it works safely.

全球大流行的病例数难以预测,而即便某种药有效,可能也不适用于所有病例。但人们已经在担心,假如其中一种有潜力的药物被证明确实有用,其供应可能会不足。为解决这些问题,世卫组织已与制药商探讨了它们能否生产出足够多的药物。通用名药物(非专利药)生产商已向该组织保证,可将利托那韦和洛匹那韦的生产剂量扩大到数以百万计,同时仍向依赖该药的HIV患者供药。与此同时,吉利德有足够多的瑞德西韦支持临床试验以及迄今为止的同情用药。该公司表示正在努力“尽快”生产更多,即使目前尚无证据表明其安全性。

In the lab, SARS-CoV-2 will continue being dissected and mulled over. Details of its tricksiness will be puzzled out, and the best bits of proteins to turn into vaccines argued over. But that is all for tomorrow. For today doctors can only hope that a combination of new understanding and not-so-new drugs will do some good. ■

在实验室里,SARS-CoV-2将继续被“解剖”和研究。有关其狡猾特性的细节将被解开,科学家们将争论把哪些蛋白质成分转化为疫苗是最佳选择。但这些都是为了明天的打算了。眼下,医生们只能希望,把对这种疾病新获得的理解和不那么新的药物结合起来会有些用处。 ■