Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Opinion Article

NPC1 as a Modulator of Disease Severity and Viral Entry of SARSCoV- 2

Author(s): Cecilia Vial, Juan Francisco Calderón and Andrés D. Klein*

Volume 21, Issue 1, 2021

Published on: 13 July, 2020

Page: [2 - 4] Pages: 3

DOI: 10.2174/1566524020666200713175426

Price: $65

Abstract

The COVID-19 plague is hitting mankind. Several viruses, including SARS-CoV-1, MERS-CoV, EBOV, and SARS-CoV-2, use the endocytic machinery to enter the cell. Genomic variants in NPC1, which encodes for the endo-lysosomal Niemann-Pick type C1 protein, restricts the host-range of viruses in bats and susceptibility to infections in humans. Lack of NPC1 and its pharmacological suppression inhibits many viral infections including SARS-CoV-1 and Type I Feline Coronavirus Infection. Antiviral effects of NPC1-inhibiting drugs for COVID-19 treatment should be explored.

Keywords: COVID-19, SARS-Cov-2, Niemann-Pick C1, modifier gene, drug repurposing, virus, infection.

« Previous Next »
[1]
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020; 181(2): 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[2]
Yang N, Shen HM. Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19. Int J Biol Sci 2020; 16(10): 1724-31.
[http://dx.doi.org/10.7150/ijbs.45498] [PMID: 32226290]
[3]
Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA 2019.
[http://dx.doi.org/10.1001/jama.2020.6019] [PMID: 32282022]
[4]
Aranda-Abreu GE, Aranda-Martínez JD, Araújo R. Use of Amantadine in a Patient With SARS CoV-2. J Med Virol 2020.
[http://dx.doi.org/10.1002/jmv.26179] [PMID: 32542661]
[5]
Klein AD, Alvarez A, Zanlungo S. The Unique Case of the Niemann-Pick Type C Cholesterol Storage Disorder. Pediatr Endocrinol Rev 2014; 1: 166-75.
[PMID: 25345099]
[6]
Takadate Y, Kondoh T, Igarashi M, et al. Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism. Cell Rep 2020; 30(2): 308-319.e5.
[http://dx.doi.org/10.1016/j.celrep.2019.12.042] [PMID: 31940478]
[7]
Ng M, Ndungo E, Kaczmarek ME, et al. Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats eLife 2015; 4e11785
[http://dx.doi.org/10.7554/eLife.11785] [PMID: 26698106]
[8]
Kondoh T, Letko M, Munster VJ, et al. Single-Nucleotide Polymorphisms in Human NPC1 Influence Filovirus Entry Into Cells J Infect Dis 2018; 218(suppl_5): S397-402
[http://dx.doi.org/10.1093/infdis/jiy248] [PMID: 30010949]
[9]
Carette JE, Raaben M, Wong AC, et al. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 2011; 477(7364): 340-3.
[http://dx.doi.org/10.1038/nature10348] [PMID: 21866103]
[10]
Côté M, Misasi J, Ren T, et al. Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection. Nature 2011; 477(7364): 344-8.
[http://dx.doi.org/10.1038/nature10380] [PMID: 21866101]
[11]
Herbert AS, Davidson C, Kuehne AI, et al. Niemann-pick C1 is essential for ebolavirus replication and pathogenesis in vivo. MBio 2015; 6(3): e00565-15.
[http://dx.doi.org/10.1128/mBio.00565-15] [PMID: 26015498]
[12]
Miller EH, Obernosterer G, Raaben M, et al. Ebola virus entry requires the host-programmed recognition of an intracellular receptor. EMBO J 2012; 31(8): 1947-60.
[http://dx.doi.org/10.1038/emboj.2012.53] [PMID: 22395071]
[13]
Jupatanakul N, Sim S, Dimopoulos G. Aedes aegypti ML and Niemann-Pick type C family members are agonists of dengue virus infection. Dev Comp Immunol 2014; 43(1): 1-9.
[http://dx.doi.org/10.1016/j.dci.2013.10.002] [PMID: 24135719]
[14]
Stoeck IK, Lee JY, Tabata K, et al. Hepatitis C Virus Replication Depends on Endosomal Cholesterol Homeostasis. J Virol 2017; 92(1): e01196-17.
[http://dx.doi.org/10.1128/JVI.01196-17] [PMID: 29046459]
[15]
Wrensch F, Winkler M, Pöhlmann S. IFITM proteins inhibit entry driven by the MERS-coronavirus spike protein: evidence for cholesterol-independent mechanisms. Viruses 2014; 6(9): 3683-98.
[http://dx.doi.org/10.3390/v6093683] [PMID: 25256397]
[16]
Takano T, Endoh M, Fukatsu H, Sakurada H, Doki T, Hohdatsu T. The cholesterol transport inhibitor U18666A inhibits type I feline coronavirus infection. Antiviral Res 2017; 145: 96-102.
[http://dx.doi.org/10.1016/j.antiviral.2017.07.022] [PMID: 28780424]
[17]
Shoemaker CJ, Schornberg KL, Delos SE, et al. Multiple cationic amphiphiles induce a Niemann-Pick C phenotype and inhibit Ebola virus entry and infection. PLoS One 2013; 8(2)e56265
[http://dx.doi.org/10.1371/journal.pone.0056265] [PMID: 23441171]
[18]
Wichit S, Hamel R, Bernard E, et al. Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking. Sci Rep 2017; 7(1): 3145.
[http://dx.doi.org/10.1038/s41598-017-03316-5] [PMID: 28600536]
[19]
Wec AZ, Nyakatura EK, Herbert AS, et al. A “Trojan horse” bispecific-antibody strategy for broad protection against ebolaviruses. Science 2016; 354(6310): 350-4.
[http://dx.doi.org/10.1126/science.aag3267] [PMID: 27608667]
[20]
Sadewasser A, Dietzel E, Michel S, et al. Anti-Niemann Pick C1 Single-Stranded Oligonucleotides With Locked Nucleic Acids Potently Reduce Ebola Virus Infection In Vitro. Mol Ther Nucleic Acids 2019; 16: 686-97.
[21]
Stadler K, Rappuoli R. SARS: Understanding the Virus and Development of Rational Therapy. Curr Mol Med 2005; 5: 677-97.

Rights & Permissions Print Cite
Article Metrics
25
2
© 2024 Bentham Science Publishers | Privacy Policy