SARS-CoV-2 is following the evolutionary rule book to perfection
新冠病毒正按进化规则趋于完美

主题变奏曲 Variations on a theme-书迷号 shumihao.com

NATURAL SELECTION is a powerful force. In circumstances that are still disputed, it took a bat coronavirus and adapted it to people instead. The result has spread around the globe. Now, in two independent but coincidental events, it has modified that virus still further, creating new variants which are displacing the original versions. It looks possible that one or other of these novel viruses will itself soon become a dominant form of SARS-CoV-2.
自然选择是一股强大的力量。在具体过程仍存争议的情形中,它让一种蝙蝠体内的冠状病毒进入人体并逐渐适应。其演变结果已在全球传播。现在,在两个独立但同时发生的事件中,它进一步修改该病毒,形成了新的变种,正在取代原始毒株。其中两个新变种之一看来可能会很快成为新冠病毒的主要毒株。

Knowledge of both became widespread in mid-December. In Britain, a set of researchers called the Covid-19 Genomics UK Consortium (COG-UK) published the genetic sequence of variant B.1.1.7, and NERVTAG, a group that studies emerging viral threats, advised the government that this version of the virus was 67-75% more transmissible than those already circulating in the country. In South Africa, meanwhile, Salim Abdool Karim, a leading epidemiologist, briefed the country on all three television channels about a variant called 501.v2 which, by then, was accounting for almost 90% of new covid-19 infections in the province of Western Cape.
人们从12月中旬开始普遍了解了这两个新变种。英国新冠肺炎基因组学联盟(Covid-19 Genomics UK Consortium,以下简称COG-UK)的研究人员公布了变种毒株B.1.1.7的基因序列,而追踪新发病毒的英国新发呼吸道病毒威胁顾问小组(NERVTAG)提醒英国政府,这种毒株的传染性比之前在英国国内流传的毒株高67%至75%。与此同时,在南非,著名流行病学家萨利姆·阿布德勒·卡里姆(Salim Abdool Karim)通过全部三个电视频道向全国通报了一种名为501.v2的变种病毒,当时南非西开普省(Western Cape)的新冠肺炎新病例中近90%是感染了这种毒株。

Britain responded on December 19th, by tightening restrictions already in place. South Africa’s response came on December 28th, in the wake of its millionth recorded case of the illness, with measures that extended a night-time curfew by two hours and reimposed a ban on the sale of alcohol. Other countries have reacted by discouraging even more forcefully than before any travel between themselves and Britain and South Africa. At least in the case of B.1.1.7, though, this has merely shut the stable door after the horse has bolted. That variant has now been detected in a score of countries besides Britain—and from these new sites, or from Britain, it will spread still further. Isolated cases of 501.v2 outside South Africa have been reported, too, from Australia, Britain, Japan and Switzerland.
英国在12月19日做出反应,收紧了现行的限制措施。南非则在12月28日确诊病例达到100万后行动起来,采取把宵禁延长两小时和重新实施禁酒令等措施。其他国家的应对方式是比之前更加严苛地限制本国与英国和南非之间的旅行。但这些不过是亡羊补牢,至少就B.1.1.7而言是这样的。英国以外的几十个国家已经检测到了这一变种,而且还会进一步从这些新地点或英国向外传播。另外,在南非以外,澳大利亚、英国、日本和瑞士也发现了感染501.v2的散发病例。

So far, the evidence suggests that despite their extra transmissibility, neither new variant is more dangerous on a case-by-case basis than existing versions of the virus. In this, both are travelling the path predicted by evolutionary biologists to lead to long-term success for a new pathogen—which is to become more contagious (which increases the chance of onward transmission) rather than more deadly (which reduces it). And the speed with which they have spread is impressive.
迄今为止的证据表明,这两个新变种尽管传染性更强,但就具体感染病例来看,都不比原来的毒株更危险。在这一点上,它们的变化符合进化生物学家对新病原体会寻求长期生存的预测,即变得传染性更强(增加继续传播的机会),而不是更致命(降低传播机会)。两者已呈现的传播速度颇为惊人。

The first sample of B.1.1.7 was collected on September 20th, to the south-east of London. The second was found the following day in London itself. A few weeks later, at the beginning of November, B.1.1.7 accounted for 28% of new infections in London. By the first week of December that had risen to 62%. It is probably now above 90%.
B.1.1.7毒株最早是在9月20日在伦敦以东南地区采集的样本中发现的。第二个样本于次日在伦敦发现。几周后,即11月初,B.1.1.7已占到伦敦新感染病例的28%。到了12月的第一周,这一比例已升至62%。现在可能已经超过90%。

Variant 501.V2 has a similar history. It began in the Eastern Cape, the first samples dating from mid-October, and has since spread to other coastal provinces.
501.v2变种也有类似的发展轨迹。它始于东开普省(Eastern Cape),第一批样本可追溯到10月中旬,此后蔓延至其他沿海省份。

The rapid rise of B.1.1.7 and 501.v2 raises several questions. One is why these particular variants have been so successful. A second is what circumstances they arose in. A third is whether they will resist any of the new vaccines in which such store is now being placed.
B.1.1.7和501.v2变种的迅速流行带来了几个问题。首先,为什么这两者能如此大行其道?其次,它们是在什么情况下产生的?第三,它们会否让现在各地正在大量订购的新疫苗失效?

The answers to the first of these questions lie in the variants’ genomes. COG-UK’s investigation of B.1.1.7 shows that it differs meaningfully from the original version of SARS-COV-2 in 17 places. That is a lot. Moreover, several of these differences are in the gene for spike, the protein by which coronaviruses attach themselves to their cellular prey. Three of the spike mutations particularly caught the researchers’ eyes.
第一个问题的答案在于变体病毒的基因组。COG-UK对B.1.1.7的研究显示,它与原始新冠病毒有17处显著突变。这是很高的变异程度。而且其中多处突变出现在突刺蛋白这一新冠病毒用来与受体细胞结合的蛋白的基因上。研究人员尤其注意到其中三处突变。

One, N501Y, affects the 501st link in spike’s amino-acid chain. This link is part of a structure called the receptor-binding domain, which stretches from links 319 to 541. It is one of six key contact points that help lock spike onto its target, a protein called ACE2 which occurs on the surface membranes of certain cells lining the airways of the lungs. The letters in the mutation’s name refer to the replacement of an amino acid called asparagine (“N”, in biological shorthand) by one called tyrosine (“Y”). That matters because previous laboratory work has shown that the change in chemical properties which this substitution causes binds the two proteins together more tightly than normal. Perhaps tellingly, this particular mutation (though no other) is shared with 501.V2.
首先是N501Y,它影响的是突刺氨基酸链的第501个位点。它是“受体结合域”(第319至541位点)中的六个关键接触点之一,有助突刺蛋白与目标——肺部气道上皮细胞表面的ACE2受体蛋白——结合。这个突变的名称中的字母表示名为酪氨酸(生物学符号为“Y”)的氨基酸替换了原本的天冬酰胺(“N”)。这一点很重要,因为之前的实验室研究表明,这种替换所导致的化学特性变化会使两种蛋白比一般情况下结合得更紧密。501.V2也有这种突变(虽然其他突变并不相同),也许很说明问题。

Golden spike
黄金突刺

B.1.1.7’s other two intriguing spike mutations are 69-70del, which knocks two amino acids out of the chain altogether, and P681H, which substitutes yet another amino acid, histidine, for one called proline at chain-link 681. The double-deletion attracted the researchers’ attention for several reasons, not the least being that it was also found in a viral variant which afflicted some farmed mink in Denmark in November, causing worries about an animal reservoir of the disease developing. The substitution is reckoned significant because it is at one end of a part of the protein called the S1/S2 furin-cleavage site (links 681-688), which helps activate spike in preparation for its encounter with the target cell. This site is absent from the spike proteins of related coronaviruses, such as the original SARS, and may be one reason why SARS-CoV-2 is so infective.
B.1.1.7的另两个耐人寻味的突刺突变是69-70del(第69和70位点的氨基酸缺失)和P681H(第681位点的氨基酸由脯氨酸变为组氨酸)。双位点氨基酸缺失引起研究人员关注的原因是多方面的,尤其是去年11月在丹麦养殖水貂中发现的新冠病毒变种中也存在这种变异,令人担忧水貂成为新冠病毒传播的动物宿主。而P681H被视为重要突变是因为它出现在突刺蛋白的S1/S2弗林蛋白酶切割位点(第681至688位点)的一个端点,这个位点可以激活突刺准备与受体细胞结合。这个位点在关联性的冠状病毒(如最初的SARS病毒)的突刺蛋白中是不存在的,这可能是新冠病毒传染性如此之强的原因之一。

The South African variant, 501.v2, has only three meaningful mutations, and all are in spike’s receptor-binding domain. Besides N501Y, they are K417N and E484K (K and E are amino acids called lysine and glutamic acid). These two other links are now the subject of intense scrutiny.
南非的501.v2变种只有三个显著突变,全部发生在突刺的受体结合域。除了N501Y之外,另两个突变是K417N和E484K(K和E分别代表赖氨酸和谷氨酸),研究人员正密切研究这两个位点的突变。

Even three meaningful mutations is quite a lot for a variant to have. Just one would be more usual. The 17 found in B.1.1.7 therefore constitute a huge anomaly. How this plethora of changes came together in a single virus is thus the second question which needs an answer.
即使只有三处显著突变,对于一个病毒变种来说也已经不少了。通常的情况是只有一处突变。因此,B.1.1.7中发现的17处突变是极为反常的现象。单个病毒是如何发生这么多变异的?这是第二个需要解答的问题。

The authors of the COG-UK paper have a suggestion. This is that, rather than being a chance accumulation of changes, B.1.1.7 might itself be the consequence of an evolutionary process—but one that happened in a single human being rather than a population. They observe that some people develop chronic covid-19 infections because their immune systems do not work properly and so cannot clear the infection. These unfortunates, they hypothesise, may act as incubators for novel viral variants.
COG-UK研究报告的作者提出了一种见解:B.1.1.7并非偶然性的变化累积结果,而可能是一个进化过程的结果——但该进化过程发生在一个人身上而非在一个人群中。他们观察到,有些人之所以会出现新冠肺炎慢性症状,是因为他们的免疫系统不能正常运作,因而无法清除病毒。研究人员猜测,这些不幸的患者可能成为了病毒新变种的孵化器。

The theory goes like this. At first, such a patient’s lack of natural immunity relaxes pressure on the virus, permitting the multiplication of mutations which would otherwise be culled by the immune system. However, treatment for chronic covid-19 often involves what is known as convalescent plasma. This is serum gathered from recovered covid patients, which is therefore rich in antibodies against SARS-CoV-2. As a therapy, that approach frequently works. But administering such a cocktail of antibodies applies a strong selection pressure to what is now a diverse viral population in the patient’s body. This, the COG-UK researchers reckon, may result in the success of mutational combinations which would not otherwise have seen the light of day. It is possible that B.1.1.7 is one of these.
他们的理论是这样的。起初,这样的病人由于缺乏先天免疫力,给病毒造成的压力较轻,令本该被免疫系统遏止的病毒变异大量出现。然而,慢性新冠肺炎的治疗往往涉及“恢复期血浆”,这是从康复的新冠患者身上采集的血清,因而富含对抗病毒的抗体。作为一种疗法,这往往是有效的。但施以多种抗体对患者体内已有的多样病毒造成了强大的选择压力。COG-UK的研究人员估计,这可能导致某些突变组合成功进化,而如果没有“恢复期血浆疗法”,这些变种可能本不会出现。B.1.1.7可能就是这么来的。

The answer to the third question—whether either new variant will resist the vaccines now being rolled out—is “probably not”. It would be a long-odds coincidence if mutations which spread in the absence of a vaccine nevertheless protected the virus carrying them from the immune response raised by that vaccine.
第三个问题——新冠病毒的这两个新变种是否能抵御现在推出的疫苗?答案是“多半不会”。在没有疫苗时就已出现的突变若能保护它们所在的病毒不被疫苗引起的免疫反应排斥,那会是极为偶然的巧合。

This is no guarantee for the future, though. The swift emergence of these two variants shows evolution’s power. If there is a combination of mutations that can get around the immune response which a vaccine induces, then there is a fair chance that nature will find it.■
但将来就说不准了。这两个变种的迅速崛起显示了进化的力量。只要存在一种突变组合能绕过疫苗所引起的免疫反应,自然选择的力量就很有可能找到它。