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墨西哥城 COVID-19 大流行第一年期间重症患者体内的 SARS-CoV-2 分子转变。

Molecular transition of SARS-CoV-2 from critical patients during the first year of the COVID-19 pandemic in Mexico City.

机构信息

Laboratorio Nacional en Salud, Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico-Degenerativas, Facultad de Estudios Superiores Iztacala, Tlalnepantla, Mexico.

Unidad de Investigación en Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico.

出版信息

Front Cell Infect Microbiol. 2023 May 16;13:1155938. doi: 10.3389/fcimb.2023.1155938. eCollection 2023.

Abstract

BACKGROUND

The SARS-CoV-2 virus has caused unprecedented mortality since its emergence in late 2019. The continuous evolution of the viral genome through the concerted action of mutational forces has produced distinct variants that became dominant, challenging human immunity and vaccine development.

AIM AND METHODS

In this work, through an integrative genomic approach, we describe the molecular transition of SARS-CoV-2 by analyzing the viral whole genome sequences from 50 critical COVID-19 patients recruited during the first year of the pandemic in Mexico City.

RESULTS

Our results revealed differential levels of the evolutionary forces across the genome and specific mutational processes that have shaped the first two epidemiological waves of the pandemic in Mexico. Through phylogenetic analyses, we observed a genomic transition in the circulating SARS-CoV-2 genomes from several lineages prevalent in the first wave to a dominance of the B.1.1.519 variant (defined by T478K, P681H, and T732A mutations in the spike protein) in the second wave.

CONCLUSION

This work contributes to a better understanding of the evolutionary dynamics and selective pressures that act at the genomic level, the prediction of more accurate variants of clinical significance, and a better comprehension of the molecular mechanisms driving the evolution of SARS-CoV-2 to improve vaccine and drug development.

摘要

背景

自 2019 年底出现以来,SARS-CoV-2 病毒导致了前所未有的死亡率。病毒基因组通过突变力量的协同作用不断进化,产生了明显的优势变体,挑战了人类的免疫力和疫苗开发。

目的和方法

在这项工作中,我们通过整合基因组方法,通过分析在墨西哥城大流行第一年招募的 50 名重症 COVID-19 患者的病毒全基因组序列,描述了 SARS-CoV-2 的分子转变。

结果

我们的结果揭示了基因组中不同水平的进化力量和特定的突变过程,这些力量和过程塑造了墨西哥大流行的前两波。通过系统发育分析,我们观察到循环 SARS-CoV-2 基因组在几个谱系中的基因组转变,从第一波流行的优势谱系转变为 B.1.1.519 变体(在刺突蛋白中 T478K、P681H 和 T732A 突变定义)在第二波中占主导地位。

结论

这项工作有助于更好地理解在基因组水平上起作用的进化动态和选择压力,预测更准确的具有临床意义的变体,并更好地理解驱动 SARS-CoV-2 进化的分子机制,以改进疫苗和药物开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5a/10227454/6e951620dbdd/fcimb-13-1155938-g001.jpg

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