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The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications.
FASEB J. 2020 06; 34(6):7253-7264.FJ

Abstract

Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID-19. By describing the life cycle of the newly emergent coronavirus, SARS-CoV-2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID-19. Moreover, we propose that Niemann-Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS-CoV-2, by highlighting key established features of the disorder that together result in an "unfavorable" host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID-19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC-like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID-19.

Authors+Show Affiliations

Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.Lipoproteins and Atherosclerosis Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

32367579

Citation

Ballout, Rami A., et al. "The Lysosome: a Potential Juncture Between SARS-CoV-2 Infectivity and Niemann-Pick Disease Type C, With Therapeutic Implications." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 34, no. 6, 2020, pp. 7253-7264.
Ballout RA, Sviridov D, Bukrinsky MI, et al. The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications. FASEB J. 2020;34(6):7253-7264.
Ballout, R. A., Sviridov, D., Bukrinsky, M. I., & Remaley, A. T. (2020). The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 34(6), 7253-7264. https://doi.org/10.1096/fj.202000654R
Ballout RA, et al. The Lysosome: a Potential Juncture Between SARS-CoV-2 Infectivity and Niemann-Pick Disease Type C, With Therapeutic Implications. FASEB J. 2020;34(6):7253-7264. PubMed PMID: 32367579.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications. AU - Ballout,Rami A, AU - Sviridov,Dmitri, AU - Bukrinsky,Michael I, AU - Remaley,Alan T, Y1 - 2020/05/05/ PY - 2020/03/23/received PY - 2020/04/21/revised PY - 2020/04/21/accepted PY - 2020/5/6/pubmed PY - 2020/7/1/medline PY - 2020/5/6/entrez KW - COVID-19 KW - angiotensin-converting enzyme-2 (ACE2) KW - cathepsins KW - cholesterol KW - lipid rafts KW - lysosomal storage diseases KW - pandemic SP - 7253 EP - 7264 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. VL - 34 IS - 6 N2 - Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID-19. By describing the life cycle of the newly emergent coronavirus, SARS-CoV-2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID-19. Moreover, we propose that Niemann-Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS-CoV-2, by highlighting key established features of the disorder that together result in an "unfavorable" host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID-19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC-like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID-19. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/32367579/The_lysosome:_A_potential_juncture_between_SARS-CoV-2_infectivity_and_Niemann-Pick_disease type_C,_with_therapeutic_implications L2 - https://doi.org/10.1096/fj.202000654R DB - PRIME DP - Unbound Medicine ER -