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SARS-CoV-2 感染的分子机制与分子治疗。

Molecular Insights of SARS-CoV-2 Infection and Molecular Treatments.

机构信息

Department of Chemistry, The University of Texas Rio Grande Valley, Edinburg, Texas 78539, USA.

Department of Molecular Science, School of Medicine, The University of Texas Rio Grande Valley, Edinburg, Texas 78539, USA.

出版信息

Curr Mol Med. 2022;22(7):621-639. doi: 10.2174/1566524021666211013121831.

Abstract

The coronavirus disease emerged in December 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome-related coronavirus 2 (SARS-CoV-2). Its rapid global spread has brought an international health emergency and urgent responses for seeking efficient prevention and therapeutic treatment. This has led to imperative needs for illustration of the molecular pathogenesis of SARS-CoV-2, identification of molecular targets or receptors, and development of antiviral drugs, antibodies, and vaccines. In this study, we investigated the current research progress in combating SARS-CoV-2 infection. Based on the published research findings, we first elucidated, at the molecular level, SARS-CoV-2 viral structures, potential viral host-cell-invasion, pathogenic mechanisms, main virus-induced immune responses, and emerging SARS-CoV-2 variants. We then focused on the main virus- and host-based potential targets and summarized and categorized effective inhibitory molecules based on drug development strategies for COVID-19 that can guide efforts for the identification of new drugs and treatment for this problematic disease. Current research and development of antibodies and vaccines were also introduced and discussed. We concluded that the main virus entry route- SARS-CoV-2 spike protein interaction with ACE2 receptors played a key role in guiding the development of therapeutic treatments against COVID-19. Four main strategies may be considered in developing molecular therapeutics, and drug repurposing is likely to be an easy, fast and low-cost approach in such a short period of time with urgent need of antiviral drugs. Additionally, the quick development of antibody and vaccine candidates has yielded promising results, but the wide-scale deployment of safe and effective COVID-19 vaccines remains paramount in solving the pandemic crisis. As new variants of the virus emerge, the efficacy of these vaccines and treatments must be closely evaluated. Finally, we discussed the possible challenges of developing molecular therapeutics for COVID-19 and suggested some potential future efforts. Despite the limited availability of literature, our attempt in this work to provide a relatively comprehensive overview of current SARS-CoV-2 studies can be helpful for quickly acquiring the key information of COVID-19 and further promoting this important research to control and diminish the pandemic.

摘要

新型冠状病毒病(COVID-19)于 2019 年 12 月出现,由严重急性呼吸系统综合征相关冠状病毒 2(SARS-CoV-2)引起。其在全球的迅速传播引发了国际卫生紧急事件,迫切需要寻求有效的预防和治疗措施。这就迫切需要阐明 SARS-CoV-2 的分子发病机制,鉴定分子靶标或受体,并开发抗病毒药物、抗体和疫苗。在本研究中,我们调查了对抗 SARS-CoV-2 感染的当前研究进展。基于已发表的研究结果,我们首先从分子水平阐明了 SARS-CoV-2 病毒结构、潜在的病毒细胞入侵、发病机制、主要病毒诱导的免疫反应和新兴的 SARS-CoV-2 变体。然后,我们专注于主要的病毒和宿主潜在靶标,并根据 COVID-19 的药物开发策略对有效抑制分子进行了总结和分类,这可以指导识别新药物和治疗这种有问题的疾病的努力。还介绍和讨论了当前的抗体和疫苗研究和开发。我们得出结论,病毒进入的主要途径——SARS-CoV-2 刺突蛋白与 ACE2 受体的相互作用,在指导针对 COVID-19 的治疗方法的开发中发挥了关键作用。在如此短的时间内,迫切需要抗病毒药物,可能会考虑四种主要的分子治疗策略,而药物重新定位可能是一种简单、快速且低成本的方法。此外,抗体和疫苗候选物的快速开发已经取得了有希望的结果,但广泛部署安全有效的 COVID-19 疫苗仍然是解决大流行危机的关键。随着病毒新变体的出现,必须密切评估这些疫苗和治疗方法的疗效。最后,我们讨论了开发 COVID-19 分子疗法的可能挑战,并提出了一些潜在的未来努力方向。尽管文献有限,但我们在这项工作中尝试提供对当前 SARS-CoV-2 研究的相对全面概述,可以帮助快速获取 COVID-19 的关键信息,并进一步推动这一重要研究以控制和减轻大流行。

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