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Published on: December 23, 2020
Hydroxypropyl-Beta-Cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication by modulating intracellular lipid dynamics
Bruno Braz Bezerra1, Keylla Vitória Gomes Macedo1, Isadora Alonso Correa1
1Laboratório de Genética e Imunologia das Infecções Virais, Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 by disrupting viral replication mechanisms and host cell processes. This cholesterol-sequestering agent shows promise as an antiviral by interfering with multiple stages of the virus life cycle.
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- Hydroxypropyl-beta-cyclodextrin (HP-BCD) is a cholesterol-sequestering agent with potential antiviral applications.
- Previous studies showed HP-BCD inhibits SARS-CoV-2 replication and infectivity.
- HP-BCD is under clinical investigation for Niemann Pick C disease.
Purpose of the Study:
- To investigate the molecular mechanisms of HP-BCD's antiviral activity against SARS-CoV-2 in vitro.
- To elucidate how HP-BCD affects host cells and viral particles during infection.
Main Methods:
- Treatment of Vero cells with HP-BCD before and after SARS-CoV-2 inoculation.
- Analysis of intracellular compartmentalization using early endosome markers.
- Assessment of nucleocapsid protein accumulation.
- Quantification of cellular cholesterol and lipid droplets.
- Detection of viral replication complexes and membrane-associated virus particles.
Main Results:
- HP-BCD treatment altered intracellular compartmentalization and promoted nucleocapsid protein accumulation.
- Reduced cholesterol and lipid droplets in HP-BCD treated cells potentially hampered double-membrane vesicle formation.
- Viral replication complexes and membrane-associated virus particles were significantly reduced.
- HP-BCD demonstrated efficacy even when administered post-adsorption, indicating interference with multiple viral life cycle stages.
Conclusions:
- HP-BCD impairs SARS-CoV-2 biosynthesis through multiple mechanisms.
- The compound exhibits minimal cytotoxicity.
- HP-BCD is a promising antiviral candidate against SARS-CoV-2.
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