Pharmacological Modulators of Autophagy as a Potential Strategy for the Treatment of COVID-19

Author(s):Show less -

Pereira, Gustavo Jose da Silva ^[1] ; Leao, Anderson Henrique Franca Figueredo ^[1] ; Erustes, Adolfo Garcia ^[1] ; Morais, Ingrid Beatriz de Melo ^[1] ; Vrechi, Talita Aparecida de Moraes ^[1] ; Zamarioli, Lucas dos Santos ^[1] ; Pereira, Cassia Arruda Souza ^[1] ; Marchioro, Lais de Oliveira ^[1] ; Sperandio, Leticia Paulino ^[1] ; Lins, Isis Valeska Freire ^[1] ; Piacentini, Mauro ^{[2, 3]} ; Fimia, Gian Maria ^{[4, 3]} ; Reckziegel, Patricia ^[1] ; Smaili, Soraya Soubhi ^[1] ; Bincoletto, Claudia ^[1]

Affiliation

^[1] Univ Fed Sao Paulo UNIFESP, Escola Paulista Med, Dept Pharmacol, BR-04044020 Sao Paulo - Brazil

^[2] Univ Roma Tor Vergata, Dept Biol, I-00133 Rome - Italy

^[3] Natl Inst Infect Dis IRCCS La Zaro Spallanzani, Dept Epidemiol & Preclin Res, I-00149 Rome - Italy

^[4] Univ Roma La Sapienza, Dept Mol Med, I-00185 Rome - Italy

• Document type: Review article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 8 APR 2021.
• Web of Science Citations: 3

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. (AU)

• FAPESP's process: 19/14722-4 - Two-Pore Channels receptors and TFEB-3 autophagy modulation in human hepatocellular carcinoma
• Grantee: Gustavo José da Silva Pereira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/10863-7 - Study of lipophagy mediated by two-pore channels receptors
• Grantee: Gustavo José da Silva Pereira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/02821-8 - Autophagy modulation by cannabinoids: neuroprotection in Parkinson's Disease
• Grantee: Soraya Soubhi Smaili
• Support Opportunities: Research Projects - Thematic Grants