We have recently reported for the first time that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) maybe a bat‐originated coronavirus with a recombination occurred within the spike (S) protein gene based on phylogenetic and simplot analyses.1 These two conclusions are supported by findings recently reported by others and are well accepted in the field of SARS‐CoV‐2 research.2-4 In addition, we speculated that snake may serve as a potential reservoir for cross‐species transmission of SARS‐CoV‐2 to humans based on limited information obtained from relative synonymous codon usage (RSCU) bias among different animal species. This later speculation was questioned by Yuzhou Gong et al and Jiating Qian et al in the preceding letters to editors. We concur with the argument that SARS‐CoV‐2 genomes used in the study were inconsistent. In fact, we used several SARS‐CoV‐2 sequences released at the time for phylogenetic analysis. However, we only included 2019 novel coronavirus (2019‐nCoV)‐MN908947 sequence in the article as usage right of the other viral genome sequences from GASID were debatable, which are similar to 2019‐nCoV‐MN908947. Regarding the inconsistent codons used for calculation of RSCU bias among different animal species, we could only use those genome reference complementary DNA (cDNAs) available from Entrez Assembly of GeneBank database. Few animal's genome reference cDNAs were not available, so we have to use all available cDNAs from Entrez Nucleotide of GeneBank database. It should be noted that some of the coding sequences from GeneBank database do not have the initiation codon ATG and multiple of three nucleotides characteristics and therefore were not included. If these sequences were incorporated into the final poly coding sequence, RSCU results would be affected by artificial frameshift mutation. The speculation that snake may serve as a potential animal reservoir was purely based on the most similar codon usage bias between SARS‐CoV‐2 andsnake, which is supported by CAI value from another study.5 Besides, ENC‐plot analysis demonstrated that codon choices of SARS‐CoV‐2 can be affected not only mutation pressure but also natural selection,5 which indicate that forecasting host reservoir only by RSCU are questionable. The true animal reservoir for SARS‐CoV‐2 remains controversial at present time and is warranted for further investigation.

我们最近首次报道，根据系统发育和简单图分析，严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 可能是一种源自蝙蝠的冠状病毒，在穗 ( S ) 蛋白基因内发生了重组。1这两个结论得到了其他人最近报告的研究结果的支持，并且在 SARS-CoV-2 研究领域被广泛接受。2-4此外，根据从不同动物物种之间的相对同义密码子使用 (RSCU) 偏差获得的有限信息，我们推测蛇可能是 SARS-CoV-2 跨物种传播给人类的潜在宿主。这一后来的推测在之前给编辑的信中受到了龚禹洲等人、钱家庭等人的质疑。我们同意研究中使用的 SARS-CoV-2 基因组不一致的论点。事实上，我们使用了当时发布的几个 SARS-CoV-2 序列进行系统发育分析。然而，我们只在文章中包含了 2019 新型冠状病毒 (2019-nCoV)-MN908947 序列，因为来自 GASID 的其他病毒基因组序列的使用权存在争议，这些序列与 2019-nCoV-MN908947 相似。关于用于计算不同动物物种间 RSCU 偏差的密码子不一致，我们只能使用来自 GeneBank 数据库的 Entrez Assembly 的那些基因组参考互补 DNA（cDNA）。很少有动物的基因组参考 cDNA 不可用，因此我们必须使用 GeneBank 数据库的 Entrez Nucleotide 中所有可用的 cDNA。需要注意的是，来自 GeneBank 数据库的一些编码序列不具有起始密码子 ATG 和三个核苷酸的倍数特征，因此不包括在内。如果将这些序列整合到最终的多编码序列中，RSCU 结果将受到人工移码突变的影响。蛇可能作为潜在动物宿主的推测纯粹是基于 SARS-CoV-2 和蛇之间最相似的密码子使用偏差，5此外，ENC 图分析表明，SARS-CoV-2 的密码子选择不仅会影响突变压力，还会影响自然选择，5这表明仅通过 RSCU 预测宿主水库是有问题的。SARS-CoV-2 的真正动物宿主目前仍存在争议，需要进一步调查。