Department of Microbiology, Pondicherry University, Puducherry 605014, India.
Department of Bioinformatics, Bharathidasan University, Tiruchirappalli 620024, India.
Virus Res. 2022 Jan 2;307:198618. doi: 10.1016/j.virusres.2021.198618. Epub 2021 Nov 3.
The second wave of COVID-19 caused by severe acute respiratory syndrome virus (SARS-CoV-2) is rapidly spreading over the world. Mechanisms behind the flee from current antivirals are still unclear due to the continuous occurrence of SARS-CoV-2 genetic variants. Brazil is the world's second-most COVID-19 affected country. In the present study, we identified the genomic and proteomic variants of Brazilian SARS-CoV-2 isolates. We identified 16 different genotypic variants were found among the 27 isolates. The genotypes of three isolates such as Bra/1236/2021 (G15), Bra/MASP2C844R2/2020 (G11), and Bra/RJ-DCVN5/2020 (G9) have a unique mutant in NSP4 (S184N), 2'O-Mutase (R216N), membrane protein (A2V) and Envelope protein (V5A). A mutation in RdRp of SARS-CoV-2, particularly the change of Pro-to Leu-at 323 resulted in the stabilization of the structure in BRA/CD1739-P4/2020. NSP4, NSP5 protein mutants are more virulent in genotype 15 and 16. A fast protein folding rate changes the structural stability and leads to escape for current antivirals. Thus, our findings help researchers to develop the best potent antivirals based on the new mutant of Brazilian isolates.
由严重急性呼吸系统综合征冠状病毒 2 型（SARS-CoV-2）引起的第二波 COVID-19 正在全球迅速蔓延。由于 SARS-CoV-2 遗传变异的不断发生，目前抗病毒药物失效的机制仍不清楚。巴西是世界上 COVID-19 感染第二严重的国家。在本研究中，我们鉴定了巴西 SARS-CoV-2 分离株的基因组和蛋白质组变异体。在 27 个分离株中发现了 16 种不同的基因型变异体。三种分离株的基因型，如 Bra/1236/2021（G15）、Bra/MASP2C844R2/2020（G11）和 Bra/RJ-DCVN5/2020（G9），在 NSP4（S184N）、2'O-甲基转移酶（R216N）、膜蛋白（A2V）和包膜蛋白（V5A）中具有独特的突变。SARS-CoV-2 的 RdRp 中的突变，特别是 323 位脯氨酸到亮氨酸的改变，导致了 BRA/CD1739-P4/2020 的结构稳定性。NSP4、NSP5 蛋白突变体在基因型 15 和 16 中具有更高的毒力。快速的蛋白质折叠速率改变了结构稳定性，导致了现有抗病毒药物的失效。因此，我们的发现有助于研究人员根据巴西分离株的新突变开发出最佳有效的抗病毒药物。
