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Updated: Sep 11, 2025

Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
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.
Abstract:
Hydroxypropyl-beta-cyclodextrin (HP-BCD) is a cholesterol sequestering agent that has been explored as a potential antiviral drug against enveloped viruses and is currently under clinical investigation for Niemann Pick C disease. We previously demonstrated that HP-BCD inhibits SARS-CoV-2 replication and infectivity by targeting both host cells and viral particles. In this study, we investigated the molecular mechanisms underlying HP-BCD antiviral activity against SARS-CoV-2 in vitro. Treatment of Vero cells with HP-BCD altered intracellular compartmentalization, as indicated by the redistribution of early endosome markers. Also, HP-BCD treatment prior to SARS-CoV-2 inoculation promoted an accumulation of nucleocapsid protein at early time points after infection. Infected cells pretreated with HP-BCD exhibited reduced cholesterol and lipid droplets content, potentially hampering the formation of new double-membrane vesicles. Consistently, viral replication complexes were scarcely detected in treated cells, which displayed disformed vesicle-like structures and lacked membrane-associated virus particles. Notably, HP-BCD also reduced viral replication when administered after virus adsorption, although with lower efficacy, indicating interference with potentially multiple stages of the SARS-CoV-2 life cycle. These findings suggest that HP-BCD effectively impairs SARS-CoV-2 biosynthesis through multiple mechanisms with minimal cytotoxicity, supporting its potential as a promising antiviral candidate.
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