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面对不断出现新变种的新冠病毒,我们能成功战胜它吗?

Can we Succeed in the Fight Against SARS-CoV-2 with its Emerging New Variants?

作者信息

Tavakol Shima, Tavakol Hani, Alavijeh Mo S, Seifalian Alexander

机构信息

Pharmidex Pharmaceutical Ltd., London, United Kingdom.

Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Curr Pharm Des. 2022;28(36):2953-2964. doi: 10.2174/1381612828666220506142117.

Abstract

In 2019, the whole world came together to confront a life-threatening virus named SARS-CoV-2, causing COVID-19 illness. The virus infected the human host by attaching to the ACE2 and CD147 receptors in some human cells, resulting in cytokine storm and death. The new variants of the virus that caused concern are Alpha, Beta, Gamma, Delta, and Epsilon, according to the WHO label. However, Pango lineages designated them as B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.429. Variants may be progressively formed in one chronic COVID-19 patient and transmitted to others. They show some differences in cellular and molecular mechanisms. Mutations in the receptor-binding domain (RBD) and N-terminal domain (NTD) lead to alterations in the host's physiological responses. They show significantly higher transmissibility rates and viral load while evading neutralizing antibodies at different rates. These effects are through mutations, deletion, and conformational alterations in the virus, resulting in the enhanced affinity of RBD to PD of ACE2 protein, virus entry, and spike conformational change. In the clinical laboratory, new variants may diagnose from other variants using specific primers for RBD or NTD. There are some controversial findings regarding the efficacy of the developed vaccines against the new variants. This research aimed to discuss the cellular and molecular mechanisms beyond COVID-19 pathogenesis, focusing on the new variants. We glanced at why the mutations and the ability to transmit the virus increase and how likely the available vaccines will be effective against these variants.

摘要

2019年,全世界共同应对一种名为严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的危及生命的病毒,它引发了2019冠状病毒病(COVID-19)。该病毒通过附着在一些人体细胞中的血管紧张素转换酶2(ACE2)和CD147受体上感染人类宿主,导致细胞因子风暴和死亡。据世界卫生组织(WHO)标注,引起关注的该病毒新变种有阿尔法、贝塔、伽马、德尔塔和伊普西龙。然而,潘多谱系将它们指定为B.1.1.7、B.1.351、P.1、B.1.617.2和B.1.429。变种可能在一名慢性COVID-19患者体内逐渐形成并传播给他人。它们在细胞和分子机制上表现出一些差异。受体结合域(RBD)和N端结构域(NTD)的突变导致宿主生理反应的改变。它们显示出显著更高的传播率和病毒载量,同时以不同速率逃避中和抗体。这些影响是通过病毒的突变、缺失和构象改变,导致RBD与ACE2蛋白的PD的亲和力增强、病毒进入以及刺突构象变化。在临床实验室中,可以使用针对RBD或NTD的特异性引物从其他变种中诊断出新变种。关于已研发疫苗对新变种的效力存在一些有争议的发现。本研究旨在讨论COVID-19发病机制背后的细胞和分子机制,重点关注新变种。我们审视了病毒突变和传播能力增加的原因,以及现有疫苗对这些变种有效的可能性。

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