Hydroxychloroquine and azithromycin used alone or combined are not effective against SARS-CoV-2 ex vivo and in a hamster model

Autor: Caroline Laprie, Caroline Solas, Jean-Sélim Driouich, Maxime Cochin, Paul-Rémi Petit, Gregory Moureau, Franck Touret, Xavier de Lamballerie, Antoine Nougairède
Jazyk: angličtina
Rok vydání: 2021
Předmět:
MOI
Multiplicity of infection

Pharmacology
EC50
50% effective concentrations

Azithromycin
Plasma
MERS-CoV
Middle East Respiratory Syndrome Coronavirus

Anti-Infective Agents
Cricetinae
Chlorocebus aethiops
HCQ
Hydroxychloroquine

SD
Standard deviation

CQ
Chloroquine

Lung
media_common
ACE2
Angiotensin-Converting enzyme 2

COVID-19
Coronavirus disease 2019

Human airway epithelium
H&E
Hematoxylin-eosin

Middle Aged
Antivirals
Drug repositioning
Drug Therapy
Combination

Female
medicine.drug
Hydroxychloroquine
Drug
HAE
Human airway epithelium

Syrian hamster
media_common.quotation_subject
BID
Bis in die

Hamster
Bronchi
Real-Time Polymerase Chain Reaction
Article
WHO
World Health Organization

REM
Remdesivir

In vivo
Virology
medicine
RT-qPCR
Quantitative real-time RT-PCR

Animals
Humans
IQ
Inhibitory quotient

TMPRSS2
Type II transmembrane serine protease

SARS-CoV
Severe Acute Respiratory Syndrome Coronavirus

Vero Cells
FCS
Fetal calf serum

LDH
Lactate dehydrogenase

Mesocricetus
business.industry
SARS-CoV-2
COVID-19
AZM
Azithromycin

respiratory tract diseases
Ex vivo
COVID-19 Drug Treatment
Coronavirus
Disease Models
Animal

SARS-CoV-2
Severe Acute Respiratory Syndrome Coronavirus 2

Viral replication
business
TCID50
Median tissue culture infectious dose
Zdroj: Antiviral Research
ISSN: 1872-9096
0166-3542
Popis: Drug repositioning has been used extensively since the beginning of the COVID-19 pandemic in an attempt to identify antiviral molecules for use in human therapeutics. Hydroxychloroquine and azithromycin have shown inhibitory activity against SARS-CoV-2 replication in different cell lines. Based on such in vitro data and despite the weakness of preclinical assessment, many clinical trials were set up using these molecules. In the present study, we show that hydroxychloroquine and azithromycin alone or combined does not block SARS-CoV-2 replication in human bronchial airway epithelia. When tested in a Syrian hamster model, hydroxychloroquine and azithromycin administrated alone or combined displayed no significant effect on viral replication, clinical course of the disease and lung impairments, even at high doses. Hydroxychloroquine quantification in lung tissues confirmed strong exposure to the drug, above in vitro inhibitory concentrations. Overall, this study does not support the use of hydroxychloroquine and azithromycin as antiviral drugs for the treatment of SARS-CoV-2 infections.
Databáze: OpenAIRE