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深入了解致病性冠状病毒SARS-CoV-2的基因组组织:对新变种出现、实验室诊断和治疗选择的启示

Insight into genomic organization of pathogenic coronaviruses, SARS-CoV-2: Implication for emergence of new variants, laboratory diagnosis and treatment options.

作者信息

Bedada Fikru B, Gorfu Gezahegn, Teng Shaolei, Neita Marguerite E

机构信息

Department of Clinical Laboratory Science, College of Nursing and Allied Health Sciences, Howard University, Washington, DC, United States.

Department of Pathology, College of Medicine, Howard University, Washington, DC, United States.

出版信息

Front Mol Med. 2022 Oct 17;2:917201. doi: 10.3389/fmmed.2022.917201. eCollection 2022.

Abstract

SARS-CoV-2 is a novel zoonotic positive-sense RNA virus (ssRNA+) belonging to the genus beta coronaviruses (CoVs) in the Coronaviridae family. It is the causative agent for the outbreak of the disease, COVID-19. It is the third CoV causing pneumonia around the world in the past 2 decades. To date, it has caused significant deaths worldwide. Notably, the emergence of new genetic variants conferring efficient transmission and immune evasion remained a challenge, despite the reduction in the number of death cases, owing to effective vaccination regimen (boosting) and safety protocols. Thus, information harnessed from SARS-CoV-2 genomic organization is indispensable for seeking laboratory diagnosis and treatment options. Here in, we review previously circulating variants of SARS-CoV-2 designated variant of concern (VOC) including the Alpha (United Kingdom), Beta (South Africa), Gamma (Brazil), Delta (India), and recently circulating VOC, Omicron (South Africa) and its divergent subvariants (BA.1, BA.2, BA.3, BA.2.12.1, BA.4 and BA.5) with BA.5 currently becoming dominant and prolonging the COVID pandemic. In addition, we address the role of computational models for mutagenesis analysis which can predict important residues that contribute to transmissibility, virulence, immune evasion, and molecular detections of SARS-CoV-2. Concomitantly, the importance of harnessing the immunobiology of SARS-CoV-2 and host interaction for therapeutic purpose; and use of an in slilico based biocomputational approaches to achieve this purpose predicting novel therapeutic agents targeting PRR such as toll like receptor, design of universal vaccine and chimeric antibodies tailored to the emergent variant have been highlighted.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是一种新型人畜共患的正链RNA病毒(单链RNA+),属于冠状病毒科的β冠状病毒属。它是疾病COVID-19爆发的病原体。它是过去20年中在全球范围内导致肺炎的第三种冠状病毒。迄今为止,它已在全球造成大量死亡。值得注意的是,尽管由于有效的疫苗接种方案(加强接种)和安全协议,死亡病例数量有所减少,但具有高效传播和免疫逃逸能力的新基因变体的出现仍然是一个挑战。因此,从SARS-CoV-2基因组结构中获取的信息对于寻求实验室诊断和治疗方案不可或缺。在此,我们回顾了先前流行的SARS-CoV-2变异株,即关注变异株(VOC),包括阿尔法(英国)、贝塔(南非)、伽马(巴西)、德尔塔(印度),以及最近流行的VOC奥密克戎(南非)及其不同的亚变体(BA.1、BA.2、BA.3、BA.2.12.1、BA.4和BA.5),目前BA.5正成为主导并延长了COVID疫情。此外,我们还讨论了计算模型在诱变分析中的作用,该模型可以预测有助于SARS-CoV-2传播性、毒力、免疫逃逸和分子检测的重要残基。同时,强调了利用SARS-CoV-2免疫生物学和宿主相互作用进行治疗的重要性;以及使用基于计算机的生物计算方法来实现这一目的——预测针对模式识别受体(PRR)(如Toll样受体)的新型治疗剂、设计通用疫苗以及针对新出现变异体定制的嵌合抗体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2bd/11328875/2fcf5fb4b164/fmmed-02-917201-g001.jpg

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