RaTG13, MP789, and RmYN02 are the strains closest to SARS-CoV-2, and their existence came to light only after the start of the pandemic. Their genomes have been used to support a natural origin of SARS-CoV-2 but after a close examination all of them exhibit several issues. We specifically address the presence in RmYN02 and closely related RacCSxxx strains of a claimed natural PAA/PVA amino acid insertion at the S1/S2 junction of their spike protein at the same position where the PRRA insertion in SARS-CoV-2 has created a polybasic furin cleavage site. We show that RmYN02/RacCSxxx instead of the claimed insertion carry a 6-nucleotide deletion in the region and that the 12-nucleotide insertion in SARS-CoV-2 remains unique among Sarbecoviruses. Also, our analysis of RaTG13 and RmYN02's metagenomic datasets found unexpected reads which could indicate possible contamination. Because of their importance to inferring SARS-CoV-2′s origin, we call for a careful reevaluation of RaTG13, MP789 and RmYN02 sequencing records and assembly methods.

中文翻译：

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SARS-CoV-2 声称的天然来源受到其相关毒株基因组序列问题的破坏

RaTG13、MP789 和 RmYN02 是最接近 SARS-CoV-2 的毒株，它们的存在是在大流行开始后才被发现的。它们的基因组已被用于支持 SARS-CoV-2 的自然起源，但经过仔细检查，它们都表现出几个问题。我们专门解决了在 RmYN02 和密切相关的 RacCSxxx 菌株中存在声称的天然 PAA/PVA 氨基酸插入在其刺突蛋白的 S1/S2 连接处，与 SARS-CoV-2 中 PRRA 插入产生多元碱基的相同位置弗林蛋白酶切割位点。我们表明，RmYN02/RacCSxxx 而非声称的插入在该区域携带 6 个核苷酸缺失，并且 SARS-CoV-2 中的 12 个核苷酸插入在 Sarbecovirus 中仍然是独一无二的。此外，我们对 RaTG13 和 RmYN02' 的分析 s 宏基因组数据集发现了可能表明可能存在污染的意外读数。由于它们对于推断 SARS-CoV-2 起源的重要性，我们呼吁对 RaTG13、MP789 和 RmYN02 测序记录和组装方法进行仔细的重新评估。