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Double-Barreled CRISPR Technology as a Novel Treatment Strategy For COVID-19.

ABSTRACT: Coronavirus is one of the causative agents for multiple human respiratory illnesses. A novel coronavirus, similar to the one that caused severe acute respiratory syndrome (SARS) in 2003, was identified as the cause of the current pandemic of coronavirus disease (COVID-19), which was first reported in late December 2019 in Wuhan, China. Since then, this novel coronavirus has spread across the globe, with most identified COVID-19 cases and fatalities occurring in the United States. In this Perspective, we discuss coronavirus pathogenicity, conventional antiviral therapies, prophylactic strategies, and novel treatment strategies for COVID-19. We highlight the application of CRISPR technology as an emerging pan-antiviral therapy. We also discuss the challenges of in vivo delivery of CRISPR components and propose novel approaches to achieve selective delivery exclusively into SARS-CoV-2-infected cells with high efficiency by hijacking the surface proteins of SARS-CoV-2.

SUBMITTER: Nalawansha DA

PROVIDER: S-EPMC7469881 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Double-Barreled CRISPR Technology as a Novel Treatment Strategy For COVID-19.

Nalawansha Dhanusha A DA Samarasinghe Kusal T G KTG

ACS pharmacology & translational science 20200827 5

Coronavirus is one of the causative agents for multiple human respiratory illnesses. A novel coronavirus, similar to the one that caused severe acute respiratory syndrome (SARS) in 2003, was identified as the cause of the current pandemic of coronavirus disease (COVID-19), which was first reported in late December 2019 in Wuhan, China. Since then, this novel coronavirus has spread across the globe, with most identified COVID-19 cases and fatalities occurring in the United States. In this Perspec ...[more]

PMID: 33062949

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Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic continues to spread globally. The rapid dispersion of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 drives an urgent need for effective treatments, especially for patients who develop severe pneumonia. The excessive and uncontrolled release of pro-inflammatory cytokines has proved to be an essential factor in the rapidity of disease progression, and some cytokines are significantly associated with adverse outcomes. Most of the upregulated cytokines signal through the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway. Therefore, blocking the exaggerated release of cytokines, including IL-2, IL-6, TNF-α, and IFNα/β/γ, by inhibiting JAK/STAT signaling will, presumably, offer favorable pharmacodynamics and present an attractive prospect. JAK inhibitors (JAKi) can also inhibit members of the numb-associated kinase (NAK) family, including AP2-associated kinase 1 (AAK1) and cyclin G-associated kinase (GAK), which regulate the angiotensin-converting enzyme 2 (ACE-2) transmembrane protein and are involved in host viral endocytosis. According to the data released from current clinical trials, JAKi treatment can effectively control the dysregulated cytokine storm and improve clinical outcomes regarding mortality, ICU admission, and discharge. There are still some concerns surrounding thromboembolic events, opportunistic infection such as herpes zoster virus reactivation, and repression of the host's type-I IFN-dependent immune repair for both viral and bacterial infection. However, the current JAKi clinical trials of COVID-19 raised no new safety concerns except a slightly increased risk of herpes virus infection. In the updated WHO guideline, Baricitinb is strongly recommended as an alternative to IL-6 receptor blockers, particularly in combination with corticosteroids, in patients with severe or critical COVID-19. Future studies will explore the application of JAKi to COVID-19 treatment in greater detail, such as the optimal timing and course of JAKi treatment, individualized medication strategies based on pharmacogenomics, and the effect of combined medications.

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Double-Barreled CRISPR Technology as a Novel Treatment Strategy For COVID-19.

Publications

Double-Barreled CRISPR Technology as a Novel Treatment Strategy For COVID-19.

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