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宿主导向疗法:新冠疫情及未来

Host directed therapies: COVID-19 and beyond.

作者信息

Tripathi Devavrat, Sodani Megha, Gupta Pramod Kumar, Kulkarni Savita

机构信息

Radiation Medicine Centre, Bhabha Atomic Research Centre, C/O Tata Memorial Hospital Annexe, Parel, Mumbai, 400012, India.

Homi Bhabha National Institute, Anushakti Nagar, Mumbai, 400094, India.

出版信息

Curr Res Pharmacol Drug Discov. 2021;2:100058. doi: 10.1016/j.crphar.2021.100058. Epub 2021 Sep 25.

Abstract

The global spread of SARS-CoV-2 has necessitated the development of novel, safe and effective therapeutic agents against this virus to stop the pandemic, however the development of novel antivirals may take years, hence, the best alternative available, is to repurpose the existing antiviral drugs with known safety profile in humans. After more than one year into this pandemic, global efforts have yielded the fruits and with the launch of many vaccines in the market, the world is inching towards the end of this pandemic, nonetheless, future pandemics of this magnitude or even greater cannot be denied. The preparedness against viruses of unknown origin should be maintained and the broad-spectrum antivirals with activity against range of viruses should be developed to curb future viral pandemics. The majority of antivirals developed till date are pathogen specific agents, which target critical viral pathways and lack broad spectrum activity required to target wide range of viruses. The surge in drug resistance among pathogens has rendered a compelling need to shift our focus towards host directed factors in the treatment of infectious diseases. This gains special relevance in the case of viral infections, where the pathogen encodes a handful of genes and predominantly depends on host factors for their propagation and persistence. Therefore, future antiviral drug development should focus more on targeting molecules of host pathways that are often hijacked by many viruses. Such cellular proteins of host pathways offer attractive targets for the development of broad-spectrum anticipatory antivirals. In the present article, we have reviewed the host directed therapies (HDTs) effective against viral infections with a special focus on COVID-19. This article also discusses the strategies involved in identifying novel host targets and subsequent development of broad spectrum HDTs.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)在全球的传播使得开发针对该病毒的新型、安全且有效的治疗药物成为阻止这一疫情大流行的必要举措。然而,新型抗病毒药物的研发可能需要数年时间,因此,现有的最佳替代方案是重新利用在人体中具有已知安全性的现有抗病毒药物。在这场疫情大流行持续一年多之后,全球的努力取得了成果,随着市场上推出多种疫苗,世界正逐渐走向这场疫情大流行的尾声。尽管如此,未来规模如此之大甚至更大的疫情大流行是不可否认的。应保持对未知来源病毒的防范准备,并开发对多种病毒具有活性的广谱抗病毒药物,以遏制未来的病毒性疫情大流行。迄今为止开发的大多数抗病毒药物都是针对病原体的特异性药物,它们靶向关键的病毒途径,缺乏针对多种病毒所需的广谱活性。病原体耐药性的激增使得我们迫切需要将治疗传染病的重点转向宿主导向因素。这在病毒感染的情况下尤为重要,因为病原体编码的基因数量有限,并且在其传播和持续存在方面主要依赖宿主因素。因此,未来的抗病毒药物研发应更多地侧重于靶向宿主途径中经常被多种病毒劫持的分子。宿主途径中的此类细胞蛋白为开发广谱预防性抗病毒药物提供了有吸引力的靶点。在本文中,我们综述了对病毒感染有效的宿主导向疗法(HDTs),特别关注了2019冠状病毒病(COVID-19)。本文还讨论了识别新型宿主靶点以及随后开发广谱HDTs所涉及的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4c/8663987/b362b2aa7bcd/ga1.jpg

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