PDF(Pubmed)
Abstract：
The animal origin of SARS-CoV-2 remains elusive, lacking a plausible evolutionary narrative that may account for its emergence. Its spike protein resembles certain segments of BANAL-236 and RaTG13, two bat coronaviruses considered possible progenitors of SARS-CoV-2. Additionally, its spike contains a furin motif, a common feature of rodent coronaviruses. To explore the possible involvement of rodents in the emergence of SARS-CoV-2 spike, we examined the crystal structures of the spike receptor-binding domains (RBDs) of BANAL-236 and RaTG13 each complexed with mouse receptor ACE2. Both RBDs have residues at positions 493 and 498 that align well with two virus-binding hotspots on mouse ACE2. Our biochemical evidence supports that both BANAL-236 and RaTG13 spikes can use mouse ACE2 as their entry receptor. These findings point to a scenario in which these bat coronaviruses may have coinfected rodents, leading to a recombination of their spike genes and a subsequent acquisition of a furin motif in rodents, culminating in the emergence of SARS-CoV-2.
摘要：
SARS-CoV-2的动物起源仍然难以捉摸，缺乏可能解释其出现的合理的进化叙事。它的刺突蛋白类似于BANAL-236和RaTG13的某些片段，这两种蝙蝠冠状病毒被认为是SARS-CoV-2的可能祖细胞。此外,它的穗包含一个弗林图案，啮齿动物冠状病毒的共同特征。探讨啮齿动物可能参与SARS-CoV-2尖峰的出现，我们检查了与小鼠受体ACE2复合的BANAL-236和RaTG13的刺突受体结合域（RBD）的晶体结构。两种RBD都在493和498位具有与小鼠ACE2上的两个病毒结合热点良好对齐的残基。我们的生化证据支持BANAL-236和RaTG13尖峰都可以使用小鼠ACE2作为其进入受体。这些发现表明，这些蝙蝠冠状病毒可能共同感染了啮齿动物，导致它们的刺突基因重组，并随后在啮齿动物中获得弗林蛋白酶图案，最终导致SARS-CoV-2的出现。
