中外科学家给出基因组学依据:新冠病毒不是实验室合成!

专家对新冠病毒基因组的两大显著特征进行了比较分析,这些分析提供了大量证据推论出:新冠病毒不太可能是实验室基因工程制造的病毒,而应该是病毒自然进化的产物。

疫情当头,关于2019新型冠状病毒来自实验室泄露的传闻此起彼伏。

日前,5位国外科学家在病毒学论坛“Virological”共同发布论文,对2019新型冠状病毒的基因组数据进行分析,指出2019新型冠状病毒不是实验室合成的,也不是一种被故意操纵的病毒。目前,论文还未经过正式的同行评议。

这5位科学家包括美国哥伦比亚大学公共卫生学院感染与免疫中心主任、被誉为“病毒猎手”的伊恩·利普金。此外还有4位来自美国斯克里普斯研究所、英国爱丁堡大学、澳大利亚悉尼大学、美国杜兰大学的生物学或免疫学研究人员。

论文指出,与其他冠状病毒相比,2019新型冠状病毒的基因组存在两个显著特征。随后文章从这两大特征入手,分析了为何2019新型冠状病毒不太可能来自实验室合成。

S蛋白与受体的结合方案,不同于人工预测

2019新型冠状病毒的第一个特征是,根据结构模型和早期生化实验,这种病毒似乎为了结合人类的ACE2受体而得到优化。

这里有必要科普一下,此前有研究发现,2019新型冠状病毒和SARS病毒都是通过刺突蛋白(S蛋白)与人体ACE2受体结合,介导病毒进入人体细胞。

中国医学科学院基础医学研究所副所长、北京协和医学院免疫学系副主任黄波介绍,S蛋白是位于冠状病毒表面的一种蛋白,放大后像钉子。ACE2则是位于人体肺部上皮细胞表面的一种蛋白。

这些国外专家提出:“SARS病毒和SARS相关冠状病毒S蛋白中的受体结合域(RBD)是病毒基因组中最容易变异的部分。这些受体结合域中的6个残基似乎对与人体ACE2受体结合以及确定宿主范围至关重要。”

论文中说,2019新型冠状病毒S蛋白基因序列中486残基处的苯丙氨酸,与SARS病毒S蛋白基因序列中的L472相对应。在SARS病毒细胞培养实验中,L472可以突变为苯丙氨酸。此前的研究预测,这是SARS病毒的受体结合域与人体ACE2受体结合的最佳方案。然而,这种位置的苯丙氨酸也存在于蝙蝠身上的一些类SARS冠状病毒中。

此外,2019新型冠状病毒受体结合域中的几个关键残基,与之前研究曾描述的与人体ACE2受体结合的最佳残基不一样。但最新研究却表明,2019新型冠状病毒与人体ACE2结合的亲和力很高。

这说明什么?“2019新型冠状病毒的S蛋白似乎是对人或类似人ACE2的自然选择的结果,从而出现了不同于预测的最佳结合方案。这有力地证明了2019新型冠状病毒不是基因工程的产物。”论文作者称。

S蛋白上的酶切位点,可以通过自然变异获得

2019新型冠状病毒的第二个特征是,在这种病毒具有高度变异性的S蛋白上,插入了12个核苷酸,而且存在一个可疑的酶切位点。

“通常情况下,存在这样的酶切位点被看作人工基因工程的痕迹。但是对禽流感病毒的研究发现,病毒在自然进化的过程中,也可以获得酶切位点。”南开大学生命科学院副教授说。

上述论文提到,这种酶切位点,在病毒快速复制和传播的自然选择环境下,例如在高度密集的鸡群中,可以在禽流感病毒血凝素(HA)蛋白的两个亚基的接合处获得。流感病毒HA蛋白在细胞培养或动物体内反复强制传代后,也可以观察到酶切位点的获得。

论文提出,通过插入或重组而获得HA蛋白中的酶切位点,可将低致病性禽流感病毒转化为高致病性禽流感病毒。同样,新城疫病毒的一个无毒分离物在鸡的连续传代过程中,可以在其融合蛋白亚基的连接处逐渐获得一个酶切位点,从而变得高度致病。

“这意味着,一旦获得酶切位点,这些病毒相当于进行了一次升级,有可能提高其传染能力。”高山说。

与这篇国外专家的论文遥相呼应,早在1月27日,高山就与多位研究人员共同在中科院科技论文预发布平台ChinaXiv上提交研究发现:2019新型冠状病毒S蛋白可能存在弗林(Furin)蛋白酶切位点。

高山介绍,他们的研究发现,2019新型冠状病毒的S蛋白可能存在弗林蛋白酶切位点,从而导致它的感染机制不同于SARS等大部分β冠状病毒。由于感染机制的改变,2019新型冠状病毒获得了更高的进入细胞的效率,这可能是其传播能力大于SARS病毒的原因之一。

“我们还意外地发现,一些禽流感病毒可以通过突变获得弗林蛋白酶切位点,这说明自然突变可以引入弗林蛋白酶切位点。”高山说。

O-聚糖结构的产生,通常需要免疫系统参与

“2019新型冠状病毒不太可能是通过实验室操作现有的SARS相关冠状病毒而出现的。”这些国外专家说。

专家们指出,如果进行了基因操纵,人们可以预期,可用于β冠状病毒的几个反向遗传系统中的一个将被使用。然而,情况并非如此,因为遗传数据显示,2019新型冠状病毒并非来自任何先前使用的病毒主干。

这几位国外专家提出了两种可能的情况来解释2019新型冠状病毒的起源:第一种是在人畜共患传染病转移之前,在非人类动物宿主中自然选择的结果;第二种是在人畜共患传染病转移之后,在人类中自然选择的结果。

那么,实验室到底有没有能力设计或合成病毒?“从技术上讲,是没有问题的。”高山说。

对此,这篇国外论文也进行了分析。“多年来,在世界各地的多个BSL-2(生物安全第二等级)实验室都进行了有关蝙蝠SARS样冠状病毒在细胞培养和/或动物模型中传代的基础研究。还记录了在BSL-2密闭环境下工作的实验室人员在实验室获得SARS病毒的实例。因此,我们必须考虑有意或无意释放2019新型冠状病毒的可能性。”论文称。

但专家们随后对这种可能性也进行了质疑。

他们指出,通过细胞培养或动物传代产生2019新型冠状病毒,需要事先分离具有高度遗传相似性的前体病毒。随后产生的酶切位点需要在细胞培养中,或者具有与人类相似的ACE2受体的动物(如雪貂)中进行密集的传代程序。然而,2019新型冠状病毒S蛋白由于存在酶切位点,导致酶切位点周围存在3个O-聚糖结构。“值得怀疑的是,O-聚糖结构的产生是否会发生在细胞培养过程中,因为这种突变通常意味着免疫系统的参与,而这种免疫系统在体外是不存在的。”这些国外专家称。

858 thoughts on “中外科学家给出基因组学依据:新冠病毒不是实验室合成!”

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