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Autophagy and SARS-CoV-2 infection: Apossible smart targeting of the autophagy pathway.
Virulence ( IF 5.5 ) Pub Date : 2020-06-22 , DOI: 10.1080/21505594.2020.1780088
Shahla Shojaei 1 , Madhumita Suresh 1 , Daniel J Klionsky 2 , Hagar Ibrahim Labouta 1, 3, 4 , Saeid Ghavami 3, 5, 6, 7, 8, 9
Affiliation  

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak resulted in 5,993,317 confirmed cases worldwide with 365,394 confirmed deaths (as of May 29th, 2020, WHO). The molecular mechanism of virus infection and spread in the body is not yet disclosed, but studies on other betacoronaviruses show that, upon cell infection, these viruses inhibit macroautophagy/autophagy flux and cause the accumulation of autophagosomes. No drug has yet been approved for the treatment of SARS-CoV-2 infection; however, preclinical investigations suggested repurposing of several FDA-approved drugs for clinical trials. Half of these drugs are modulators of the autophagy pathway. Unexpectedly, instead of acting by directly antagonizing the effects of viruses, these drugs appear to function by suppressing autophagy flux. Based on the established cross-talk between autophagy and apoptosis, we speculate that over-accumulation of autophagosomes activates an apoptotic pathway that results in apoptotic death of the infected cells and disrupts the virus replication cycle. However, administration of the suggested drugs are associated with severe adverse effects due to their off-target accumulation. Nanoparticle targeting of autophagy at the sites of interest could be a powerful tool to efficiently overcome SARS-CoV-2 infection while avoiding the common adverse effects of these drugs.



中文翻译:


自噬和 SARS-CoV-2 感染:自噬途径的可能智能靶向。


 抽象的


严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)爆发导致全球确诊病例 5,993,317 例,确诊死亡 365,394 例(截至 2020 年 5 月 29,世界卫生组织)。病毒感染和在体内传播的分子机制尚未公开,但对其他β冠状病毒的研究表明,在细胞感染后,这些病毒会抑制巨自噬/自噬流并导致自噬体的积累。尚未批准用于治疗 SARS-CoV-2 感染的药物;然而,临床前研究表明将 FDA 批准的几种药物重新用于临床试验。这些药物中有一半是自噬途径的调节剂。出乎意料的是,这些药物似乎不是通过直接拮抗病毒的作用来发挥作用,而是通过抑制自噬流来发挥作用。基于自噬和细胞凋亡之间已建立的交互作用,我们推测自噬体的过度积累会激活细胞凋亡途径,导致受感染细胞凋亡并破坏病毒复制周期。然而,由于药物的脱靶积累,使用建议的药物会产生严重的副作用。纳米颗粒靶向感兴趣位点的自噬可能是有效克服 SARS-CoV-2 感染的强大工具,同时避免这些药物的常见副作用。

更新日期:2020-06-22
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