SARS-CoV-2的近端起源

結論

在全球COVID-19公共衛生緊急情況中，有理由懷疑大流行病的起因是什麼。對動物病毒如何越過物種邊界來如此有效地感染人類的​​詳細了解將有助於預防未來的人畜共患病事件。例如，如果SARS-CoV-2已預先適應另一種動物，則存在將來再次出苗事件的風險。相反，如果適應性過程發生在人類中，則即使發生了重複的人畜共患病轉移，如果沒有相同的一系列突變，它們也不可能起飛。此外，鑒定在動物中傳播的SARS-CoV-2的最親近的病毒親屬將極大地有助於病毒功能的研究。確實，RaTG13蝙蝠序列的可用性幫助揭示了關鍵的RBD突變和多鹼基切割位點。這裡描述的基因組特徵可以部分解釋SARS-CoV-2在人類中的傳染性和傳播性。儘管有證據表明SARSCoV-2不是故意操縱的病毒，但目前尚無法證明或證明此處描述的其起源的其他理論。但是，由於我們在自然界中的相關冠狀病毒中觀察到了所有值得注意的SARS-CoV-2特徵，包括優化的RBD和多鹼基切割位點，因此我們認為任何類型的基於實驗室的方案都是不合理的。更多的科學數據可能使證據的平衡偏向於一種假設勝過另一種假設。從動物來源獲得相關的病毒序列將是揭示病毒起源的最確定的方法。例如，將來觀察到來自動物的SARS-CoV-2-like病毒中的中間或完全形成的多價切割位點將為自然選擇假設提供進一步的支持。獲得有關SARSCoV-2的更多遺傳和功能數據，包括動物研究，也將有所幫助。同樣，對SARS-CoV-2潛在中間宿主的鑒定以及對非常早期病例的病毒測序也將具有很高的信息意義。無論通過自然選擇產生SARSCoV-2的確切機制是什麼，對人類和其他動物進行肺炎的持續監測顯然至關重要

Conclusions

In the midst of the global COVID-19 public-health emergency, it is reasonable to wonder why the origins of the pandemic matter. Detailed understanding of how an animal virus jumped species boundaries to infect humans so productively will help in the prevention of future zoonotic events. For example, if SARS-CoV-2 pre-adapted in another animal species, then there is the risk of future re-emergence events. In contrast, if the adaptive process occurred in humans, then even if repeated zoonotic transfers occur, they are unlikely to take off without the same series of mutations. In addition, identifying the closest viral relatives of SARS-CoV-2 circulating in animals will greatly assist studies of viral function. Indeed, the availability of the RaTG13 bat sequence helped reveal key RBD mutations and the polybasic cleavage site. The genomic features described here may explain in part the infectiousness and transmissibility of SARS-CoV-2 in humans. Although the evidence shows that SARSCoV-2 is not a purposefully manipulated virus, it is currently impossible to prove or disprove the other theories of its origin described here. However, since we observed all notable SARS-CoV-2 features, including the optimized RBD and polybasic cleavage site, in related coronaviruses in nature, we do not believe that any type of laboratorybased scenario is plausible. More scientific data could swing the balance of evidence to favor one hypothesis over another. Obtaining related viral sequences from animal sources would be the most definitive way of revealing viral origins. For example, a future observation of an intermediate or fully formed polybasic cleavage site in a SARS-CoV-2-like virus from animals would lend even further support to the natural-selection hypotheses. It would also be helpful to obtain more genetic and functional data about SARSCoV-2, including animal studies. The identification of a potential intermediate host of SARS-CoV-2, as well as sequencing of the virus from very early cases, would similarly be highly informative. Irrespective of the exact mechanisms by which SARSCoV-2 originated via natural selection, the ongoing surveillance of pneumonia in humans and other animals is clearly of utmost importance