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Publication . Preprint . Article . 2022

Moxidectin and ivermectin inhibit sars-cov-2 replication in vero e6 cells but not in human primary airway epithelium cells

Nilima Dinesh Kumar; Bram M. ter Ellen; Ellen M Bouma; Berit Troost; Denise P. I. van de Pol; Heidi van der Ende-Metselaar; Djoke van Gosliga; +7 Authors
Open Access
English
Abstract
AbstractAntiviral therapies are urgently needed to treat and limit the development of severe COVID-19 disease. Ivermectin, a broad-spectrum anti-parasitic agent, has been shown to have anti-SARS-CoV-2 activity in Vero cells at a concentration of 5 µM. These in vitro results triggered the investigation of ivermectin as a treatment option to alleviate COVID-19 disease. In April 2021, the World Health Organization stated, however, the following: “the current evidence on the use of ivermectin to treat COVID-19 patients is inconclusive”. It is speculated that the in vivo concentration of ivermectin is too low to exert a strong antiviral effect. Here, we performed a head-to head comparison of the antiviral activity of ivermectin and a structurally related, but metabolically more stable, moxidectin in multiple in vitro models of SARS-CoV-2 infection, including physiologically relevant human respiratory epithelial cells. Both moxidectin and ivermectin exhibited antiviral activity in Vero E6 cells. Subsequent experiments revealed that the compounds predominantly act on a step after virus cell entry. Surprisingly, however, in human airway-derived cell models, moxidectin and ivermectin failed to inhibit SARS-CoV-2 infection, even at a concentration of 10 µM. These disappointing results calls for a word of caution in the interpretation of anti-SARS-CoV-2 activity of drugs solely based on Vero cells. Altogether, these findings suggest that, even by using a high-dose regimen of ivermectin or switching to another drug in the same class are unlikely to be useful for treatment against SARS-CoV-2 in humans.
Subjects by Vocabulary

Medical Subject Headings: parasitic diseases

Microsoft Academic Graph classification: Moxidectin chemistry.chemical_compound chemistry In vitro Virus Ivermectin medicine.drug medicine Respiratory epithelium business.industry business In vivo Vero cell Pharmacology Drug media_common.quotation_subject media_common

Subjects

Infectious Diseases, Pharmacology (medical), Pharmacology, Antiviral Agents, moxidectin, ivermectin, antiviral, SARS-CoV-2, ALI, in vitro

Funded by
EC| PRONKJEWAIL
Project
PRONKJEWAIL
Protecting patients with enhanced susceptibility to infections
  • Funder: European Commission (EC)
  • Project Code: 713660
  • Funding stream: H2020 | MSCA-COFUND-DP
Validated by funder
Related to Research communities
COVID-19
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