Has Ivermectin Virus-Directed Effects against SARS-CoV-2? Rationalizing the Action of a Potential Multitarget Antiviral Agent
Francés-Monerris et al.,
Has Ivermectin Virus-Directed Effects against SARS-CoV-2? Rationalizing the Action of a Potential Multitarget..,
ChemRxiv, doi:10.26434/chemrxiv.12782258.v1 (Preprint)
In silico study showing that ivermectin is capable of interfering in different key steps of the SARS-CoV-2 replication cycle.
Francés-Monerris et al., 8 Oct 2020, preprint, 8 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: Has Ivermectin Virus-Directed Effects against SARS-CoV-2?
Rationalizing the Action of a Potential Multitarget Antiviral Agent
Antonio Francés-Monerris,1,2,* Cristina García-Iriepa,3,4,* Isabel Iriepa,4,5 Cécilia Hognon,1 Tom Miclot,1,6
Giampaolo Barone,6 Antonio Monari,1,* and Marco Marazzi3,4,*
1 Université de Lorraine and CNRS, LPCT UMR 7019, F-54000 Nancy, France.
2 Departament de Química Física, Universitat de València, 46100 Burjassot, Spain.
3 Department of Analytical Chemistry, Physical Chemistry and Chemical Engineering, Universidad de Alcalá, Ctra. Madrid-Barcelona, Km 33,600, 28871 Alcalá
de Henares, Madrid, Spain.
4 Chemical Research Institute “Andrés M. del Río” (IQAR), Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.
5 Department of Organic and Inorganic Chemistry, Universidad de Alcalá, Ctra. Madrid-Barcelona, Km 33,600, 28871 Alcalá de Henares, Madrid, Spain.
6 Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Università degli Studi di Palermo, Viale delle Scienze, 90128 Palermo,
Italy.
*A. F.-M.: antonio.frances@uv.es, C. G.-I.: cristina.garciai@uah.es, A. M.: Antonio.monari@univ-lorraine.fr, M. M.: marco.marazzi@uah.es
Supporting information for this article is given via a link at the end of the document.
that have required the implementation of severe social distancing
measures and movement restrictions, including full lock-down,
causing significant social and economic damage.
In this context of emergency, the international scientific
community is reacting with rapid responses to enhance the
knowledge of the virus’s fundamental processes and hence
facilitate the control of the pandemic. This includes a very rapid
sequencing of SARS-CoV-2 genome, solving the structures of
key viral proteins, modeling of the pandemic spread to assist
public decision, and developing better detection tests,[4]
vaccines,[5] and effective treatments.[6] Due to the urgency
posed by the pandemic, an efficient and relatively fast strategy to
obtain suitable therapeutic agents consists in exploring the antiSARS-CoV-2 activity of drugs already approved for human use,[7]
in a drug repurposing framework. Since the safety profiles of the
candidates are well known, only the antiviral efficacy remains to
be assessed, thus strongly reducing the time required for clinical
tests and approval.
A drug that has shown promising results is the broad-spectrum
antiparasitic ivermectin (Figure 1), which has been shown to
inhibit SARS-CoV-2 replication in cell cultures with an IC50 of ~2
μM.[8] In particular, the action of ivermectin results in 99.8%
reduction of cell associated viral RNA in 24 hours, while a ~5000fold decrease of the viral RNA content is observed after 48 hours
with a maintaining of the effect at 72 hours. Recently, Yang et al[9]
have shown that ivermectin is a host-directed agent, i.e. the main
targets of the drug are not in the pathogen but in the host cell.
This is coherent with the broad antiviral activity observed against
HIV, influenza, dengue virus, Zika, and other flaviviruses.[10]
Ivermectin inhibits the transport of viral proteins into cellular nuclei
mediated by importin α/β1 carriers, an import process related to
the suppression of the host immune response by impairing mRNA
function.[9] This pathogen-independent mechanism suggests that
only very low concentrations of ivermectin could be sufficient to
control SARS-CoV-2 infection.[11] A recent report have
questioned that the plasma..
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