Spratt Austin N, Kannan Saathvik R, Woods Lucas T, Weisman Gary A, Quinn Thomas P, Lorson Christian L, Sönnerborg Anders, Byrareddy Siddappa N, Singh Kamal
bioRxiv. 2021 Mar 24:2021.03.24.436850. doi: 10.1101/2021.03.24.436850.
Global spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has triggered unprecedented scientific efforts, as well as containment and treatment measures. Despite these efforts, SARS-CoV-2 infections remain unmanageable in some parts of the world. Due to inherent mutability of RNA viruses, it is not surprising that the SARS-CoV-2 genome has been continuously evolving since its emergence. Recently, four functionally distinct variants, B.1.1.7, B.1.351, P.1 and CAL.20C, have been identified, and they appear to more infectious and transmissible than the original (Wuhan-Hu-1) virus. Here we provide evidence based upon a combination of bioinformatics and structural approaches that can explain the higher infectivity of the new variants. Our results show that the greater infectivity of SARS-CoV-2 than SARS-CoV can be attributed to a combination of several factors, including alternate receptors. Additionally, we show that new SARS-CoV-2 variants emerged in the background of D614G in Spike protein and P323L in RNA polymerase. The correlation analyses showed that all mutations in specific variants did not evolve simultaneously. Instead, some mutations evolved most likely to compensate for the viral fitness.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)在全球的传播引发了前所未有的科研努力以及防控和治疗措施。尽管付出了这些努力,但SARS-CoV-2感染在世界某些地区仍然难以控制。由于RNA病毒固有的变异性,SARS-CoV-2基因组自出现以来一直在持续进化也就不足为奇了。最近,已鉴定出四种功能不同的变体,即B.1.1.7、B.1.351、P.1和CAL.20C,并发现它们似乎比原始(武汉-胡-1)病毒更具传染性和传播性。在此,我们基于生物信息学和结构方法相结合提供证据,以解释新变体更高的传染性。我们的结果表明,SARS-CoV-2比SARS-CoV具有更高传染性可归因于多种因素的组合, 包括替代受体。此外,我们表明新的SARS-CoV-2变体出现在刺突蛋白中的D614G和RNA聚合酶中的P323L背景下。相关性分析表明,特定变体中的所有突变并非同时进化。相反,一些突变的进化很可能是为了补偿病毒的适应性。