Moxidectin and ivermectin inhibit SARS-CoV-2 replication in Vero E6 cells but not in human primary airway epithelium cells
et al., Antimicrobial Agents and Chemotherapy, doi:10.1128/AAC.01543-21
(date from earlier preprint) (In Vitro)
Dinesh Kumar et al.
, Moxidectin and ivermectin inhibit SARS-CoV-2 replication in Vero E6 cells but not in human primary airway..
, Antimicrobial Agents and Chemotherapy, doi:10.1128/AAC.01543-21 (date from earlier preprint) (In Vitro)
study showing moxidectin and ivermectin exhibited antiviral activity in Vero E6 cells. Authors indicate that no statistically significant effect was seen in Calu-3/PBEC cells, however Figure 3 shows a dose dependent reduction with ivermectin and moxidectin, and the actual values are not provided. Calu-3 is one of many cell lines derived from human lung carcinomas [journals.physiology.org]
. Calu-3 cells resemble serous gland cells. They do not express 15-lipoxygenase, an enzyme specifically localized to the surface epithelium, but they do express secretory component, secretory leukocyte protease inhibitor, lysozyme, and lactoferrin, all markers of serous gland cells. [journals.physiology.org]
note that the absence of systemic inflammation, circulatory factors, and other paracrine systemic influences is a potential limitation of the isolated cell system.15 In Vitro studies
support the efficacy of ivermectin [Boschi, Caly, Croci, De Forni, Delandre, Jeffreys, Jitobaom, Jitobaom (B), Li, Liu, Mody, Mountain Valley MD, Segatori, Surnar, Yesilbag]
Dinesh Kumar et al., 17 Mar 2021, peer-reviewed, 14 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: ANTIVIRAL AGENTS
Moxidectin and Ivermectin Inhibit SARS-CoV-2 Replication in Vero
E6 Cells but Not in Human Primary Bronchial Epithelial Cells
Nilima Dinesh Kumar,a,b Bram M. ter Ellen,b Ellen M. Bouma,b Berit Troost,b Denise P. I. van de Pol,b Heidi H. van der Ende-Metselaar,b
Djoke van Gosliga,c Leonie Apperloo,d Orestes A. Carpaij,e Maarten van den Berge,e Martijn C. Nawijn,d Ymkje Stienstra,f
Izabela A. Rodenhuis-Zybert,b Jolanda M. Smitb
Department of Biomedical Sciences of Cells & Systems, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Department of Pediatrics, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, GRIAC Research Institute, Groningen, The
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, GRIAC Research Institute, Groningen, The Netherlands
Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, GRIAC Research Institute, Groningen, The Netherlands
Department of Internal Medicine/Infectious Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Nilima Dinesh Kumar, Bram M. ter Ellen and Ellen M. Bouma contributed equally to this work, and Izabela A. Rodenhuis-Zybert and Jolanda M. Smit contributed equally to this work.
Author order was determined based on contribution to preparing the manuscript.
Antiviral 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 m M. These limited in vitro results triggered the investigation of ivermectin as a
treatment option to alleviate COVID-19 disease. However, in April 2021, the World
Health Organization stated 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 the
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 these compounds predominantly act on
the steps following virus cell entry. Surprisingly, however, in human-airway-derived
cell models, both moxidectin and ivermectin failed to inhibit SARS-CoV-2 infection,
even at concentrations of 10 m M. These disappointing results call for a word of caution in the interpretation of anti-SARS-CoV-2 activity of drugs solely based on their
activity in Vero cells. Altogether, these ﬁndings suggest that even using a high-dose
regimen of ivermectin, or switching to another drug in the same class, is unlikely to
be useful for treatment of SARS-CoV-2 in humans.
KEYWORDS moxidectin, ivermectin, antiviral, SARS-CoV-2, ALI, in vitro
ithin less than 1.5 years, the pandemic SARS coronavirus 2 (SARS-CoV-2) has
infected over 153 million individuals and resulted in over 3.2..
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