Saeed Amanj A
School of Medicine, University of Sulaimani, Sulaymaniyah, IRQ.
Cureus. 2021 Oct 22;13(10):e18981. doi: 10.7759/cureus.18981. eCollection 2021 Oct.
From the currently available next-generation sequencing data, we have tried to analyze different theories on the origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and thereby to identify the origin of its intermediate host. Genome sequence-based phylogenetic analysis and multiple sequence alignment were performed.
We used the Virus Pathogen Resource (ViPR) platform for phylogenetic analysis and the MUltiple Sequence Comparison by Log- Expectation (MUSCLE) algorithm for whole genome sequence alignment of SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), BJ01, Middle East respiratory syndrome coronavirus (MERS-CoV), bat coronavirus RaTG13, and pangolin coronavirus.
From these two analyses, we have found that RaTG13 is the closest relative to SARS-CoV-2 and not the pangolin coronavirus in spite of having sequence homology-based similarity in the genes. Comparing the RNA-dependent RNA polymerase (RdRp) and interacting spike (S) protein that interacts directly with the host human angiotensin-converting enzyme 2 (hACE2), the bat coronavirus RaTG13 was found to be the closest relative to SARS-CoV-2. Through multiple sequence alignment of the amino acid sequences, we found the furin-like cleavage site RRARS only in SARS-CoV-2 at the junction of the two subunits S1/S2 of the spike protein.
The possible zoonotic transfer that has happened in SARS-CoV-2 seems to not be from the pangolin, but RaTG13 remains closest relative to SARS-CoV-2. Further studies, such as systematic reviews of the literature and meta-analyses, are needed to reach a conclusion regarding the evolutionary trajectory of the SARS-CoV-2 outbreak.
基于现有的下一代测序数据，我们试图分析关于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）起源的不同理论，从而确定其中间宿主的起源。进行了基于基因组序列的系统发育分析和多序列比对。
我们使用病毒病原体资源（ViPR）平台进行系统发育分析，并使用对数期望多重序列比较（MUSCLE）算法对SARS-CoV-2、严重急性呼吸综合征冠状病毒（SARS-CoV）、BJ01、中东呼吸综合征冠状病毒（MERS-CoV）、蝙蝠冠状病毒RaTG13和穿山甲冠状病毒的全基因组序列进行比对。
通过这两项分析，我们发现尽管穿山甲冠状病毒在基因上具有基于序列同源性的相似性，但RaTG13是与SARS-CoV-2亲缘关系最近的，而非穿山甲冠状病毒。比较与宿主人类血管紧张素转换酶2（hACE2）直接相互作用的RNA依赖性RNA聚合酶（RdRp）和刺突（S）蛋白，发现蝙蝠冠状病毒RaTG13是与SARS-CoV-2亲缘关系最近的。通过对氨基酸序列的多序列比对，我们仅在SARS-CoV-2的刺突蛋白两个亚基S1/S2的连接处发现了类弗林蛋白酶切割位点RRARS。
SARS-CoV-2中可能发生的人畜共患病传播似乎并非来自穿山甲，而RaTG13仍是与SARS-CoV-2亲缘关系最近的。需要进一步的研究，如对文献的系统评价和荟萃分析，以得出关于SARS-CoV-2疫情进化轨迹的结论。
