Autophagy and SARS-CoV-2 infection: A possible smart targeting of the autophagy pathway

Virulence

Saeid Ghavami¹  Shahla Shojaei²  Madhumita Suresh²  Hagar Ibrahim Labouta³  Daniel J. Klionsky⁴ 

[1] Children’s Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canad;Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canad;Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egyp;Research Institute in Oncology and Hematology, CancerCare Manitoba, University of Manitoba, Winnipeg, Manitoba, Canad;Autophagy Research Centre, Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Ira;Faculty of Medicine, Katowice School of Technology, Katowice, Polan;College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canad;College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canad;Children’s Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canad;Biomedical Engineering Program, University of Manitoba, Winnipeg, Manitoba, Canad;Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, US;

关键词: Apoptosis;    autophagy flux;    drug targeting;    macroautophagy;    nanomedicine;    nanoparticles;    SARS-CoV-2;   

DOI  :  10.1080/21505594.2020.1780088

来源: Taylor & Francis

【 摘 要 】

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.

【 授权许可】

CC BY