Hydroxychloroquine: mechanism of action inhibiting SARS-CoV2 entry

BioRxiv : the Preprint Server for Biology
Zixuan YuanScott B Hansen

Abstract

SARS-coronavirus 2 (SARS-CoV-2) is currently causing a worldwide pandemic. Potential drugs identified for the treatment of SARS-CoV-2 infection include chloroquine (CQ), its derivative hydroxychloroquine (HCQ), and the anesthetic propofol. Their mechanism of action in SARS-CoV-2 infection is poorly understood. Recently, anesthetics, both general and local, were shown to disrupt ordered lipid domains. These same lipid domains recruit the SARS-CoV-2 surface receptor angiotensin converting enzyme 2 (ACE2) to an endocytic entry point and their disruption by cholesterol depletion decreases ACE2 recruitment and viral entry. Viral entry was determined using a SARS-CoV-2 pseudovirus (SARS2-PV) and a luciferase reporter gene expressed by the virus after treatment of the cells with 50 μM propofol, tetracaine, HCQ, and erythromycin. HCQ disruption of monosialotetrahexosylganglioside1 (GM1) lipid rafts, phosphatidylinositol 4,5-bisphosphate (PIP 2 ) domains, and ACE2 receptor at nanoscale distances was monitored by direct stochastic reconstruction microscopy (dSTORM). Cells were fixed, permeabilized, and then labeled with either fluorescent cholera toxin B (CTxB) or antibody and then fixed again prior to imaging. Cluster analysis of dSTORM...Continue Reading

Citations

Jan 6, 2021·Emerging Microbes & Infections·Zhenyu ZhaoYong Lin
Dec 10, 2020·Clinical and Molecular Allergy : CMA·Giuseppe MurdacaSimone Negrini
Feb 23, 2021·Frontiers in Cell and Developmental Biology·Maurizio SoriceVincenzo Mattei

Methods Mentioned

BETA
sedation
ELISA
enzyme-linked immunosorbent assay
glycosylation
Assay
Super Resolution Microscopy

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