Abstract
The family of coronaviruses (CoVs) uses the autophagy machinery of host cells to promote their growth and replication; thus, this process stands out as a potential target to combat COVID-19. Considering the different roles of autophagy during viral infection, including SARS-CoV-2 infection, in this review, we discuss several clinically used drugs that have effects at different stages of autophagy. Among them, we mention (1) lysosomotropic agents, which can prevent CoVs infection by alkalinizing the acid pH in the endolysosomal system, such as chloroquine and hydroxychloroquine, azithromycin, artemisinins, two-pore channel modulators and imatinib; (2) protease inhibitors that can inhibit the proteolytic cleavage of the spike CoVs protein, which is necessary for viral entry into host cells, such as camostat mesylate, lopinavir, umifenovir and teicoplanin and (3) modulators of PI3K/AKT/mTOR signaling pathways, such as rapamycin, heparin, glucocorticoids, angiotensin-converting enzyme inhibitors (IECAs) and cannabidiol. Thus, this review aims to highlight and discuss autophagy-related drugs for COVID-19, from in vitro to in vivo studies. We identified specific compounds that may modulate autophagy and exhibit antiviral properties. We hope that research initiatives and efforts will identify novel or “off-label” drugs that can be used to effectively treat patients infected with SARS-CoV-2, reducing the risk of mortality.
Highlights
It has been suggested that since SARS-CoV-2 contains structural components that are similar to other viruses, including human immunodeficiency virus (HIV), it is plausible that this antiviral therapy could be used to treat patients with COVID-19 [176]
Due to its rapid spread, high lethality and impact on health systems, the COVID-19 pandemic caused by SARS-CoV-2 represents one of the most significant challenges ever faced by the modern world
We discussed the potential of autophagy inhibitors in the treatment of COVID-19 infection, and offered a justification for the mechanism related to autophagy for the potential antiviral activity of these drugs
Summary
Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by the infectious coronavirus SARS-CoV-2 [1,2]. It was first described by the Chinese Center for Disease Control and Prevention in December 2019 as a mysterious viral respiratory disease that emerged in the city of Wuhan, Hubei province, China. In 2 September 2020, WHO recommended corticosteroids as an effective treatment for seriously ill COVID-19 patients, but global deaths kept rising reaching 1 million by the end of the same month. By the end of February 2021, the number of global deaths related to COVID-19 was close to 2.5 million
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