Pós-Graduation Program in Clinical Oncology, Stem Cells and Cell Therapy, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Laboratory of Molecular Biology, Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
J Med Virol. 2020 Nov;92(11):2607-2615. doi: 10.1002/jmv.26072. Epub 2020 Jun 16.
The novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2 is an international public health emergency. Until now, the intermediate host and mechanisms of the interspecies jump of this virus are unknown. Phylogenetic analysis of all available bat CoV complete genomes was performed to analyze the relationships between bat CoV and SARS-CoV-2. To suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals that were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions that may have permitted the adaptation of SARS-CoV-2 to the human host. The phylogenetic analysis demonstrated that SARS-CoV-2 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS-CoV-2, bat RaTG13, and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS-CoV-2 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS-CoV-2 tropism to human cells. Our analysis shows the tight relationship between SARS-CoV-2 and bat SARS-like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S-binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function.
新型冠状病毒(CoV),严重急性呼吸系统综合征(SARS)-CoV-2 是国际公共卫生紧急事件。到目前为止,这种病毒的中间宿主和种间跳跃的机制尚不清楚。对所有可用的蝙蝠 CoV 完整基因组进行系统发育分析,以分析蝙蝠 CoV 与 SARS-CoV-2 之间的关系。为了提出可能的中间宿主,还对来自假设在中国市场商业化的动物的 CoV 基因组进行了另一个系统发育重建。此外,还进行了突变分析,以提出可能允许 SARS-CoV-2 适应人类宿主的基因组区域。系统发育分析表明,SARS-CoV-2 与蝙蝠 CoV 分离株 RaTG13 形成一个聚类。还观察到蝙蝠分离株之间可能发生的 CoV 种间跳跃。来自不同动物的 CoV 株重建的系统发育树表明,SARS-CoV-2、蝙蝠 RaTG13 和穿山甲 CoV 基因组形成一个单系群,表明穿山甲可能被建议为 SARS-CoV-2 的中间宿主。观察到 S 基因 S1 部分的三个 AA 取代,其中一些与 S 蛋白的结构修饰相关,这可能促进了 SARS-CoV-2 对人类细胞的嗜性。我们的分析表明,SARS-CoV-2 与蝙蝠 SARS 样株之间存在紧密的关系。它还假设穿山甲可能是感染的中间宿主。在 S 结合蛋白中观察到的一些 AA 取代可能作为人类可能的适应性突变,但需要更多的研究来阐明它们的功能。