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Hydroxychloroquine and preclinical studies: a world tour in five experimental models



An international study involving IDMIT's (CEA-Jacob) Roger Le Grand and other researchers from more than 80 countries concluded that chloroquine (CQ) and hydroxychloroquine (HCQ) likely provide no clinical benefits in the treatment of COVID-19.

For their study published in Nature Communications, the group of scientific experts reviewed the various tests done with these compounds in in vitro and in vivo models of SARS-CoV-2. Despite earlier in vitro results determined in cell lines, the international team found that neither CQ nor HCQ were efficacious against the infection.

Published on 28 August 2020

As part of the global response to the COVID-19 pandemic, the World Health Organization called upon a number of scientific experts, including Roger Le Grand (IDMIT/CEA-Jacob), to create an international work group for sharing scientific data, mutualizing R&D efforts, accelerating the development and production of novel COVID-19 diagnostics, therapies and vaccines, and ensuring equal access to them1.

Among the work group's initial reflections was to reconsider a range of medicines authorized at least temporarily for COVID-19 treatment. Among those treatments, chloroquine (CQ) and hydroxychloroquine (HCQ) stood out for the numerous in vitro and in vivo tests done for them.

HCQ and CQ are both used to prevent and treat malaria in world regions where the disease is endemic. Because of their anti-inflammatory properties, these compounds are also used to treat autoimmune disorders such as lupus or rheumatoid arthritis. During the Ebola virus disease (EVD) epidemic in western Africa, they garnered a great amount of media attention after several studies reported a possible association between CQ treatment and improved EVD symptomatology. With the COVID-19 pandemic, CQ and HCQ again entered the limelight as possible treatments against SARS-CoV-2 infection, leading to a number of clinical trials either completed or underway.

In their article published in Nature Communications, the work group's scientists underlined the results of multiple studies suggesting that CQ and HCQ should have never been considered as efficacious treatments for COVID-19. Some of those studies were supervised by laboratories for which the experts worked. The associated projects deployed various experimental models of SARS-CoV-2 infection :

  • Lung-on-a-chip technologies, developed by the Wyss Institute, marketed by Emulate Inc. and used to evaluate the effects of CQ on viral replication;
  • A hamster experimental model, known to be more susceptible to infection than murine models and used to test the effects of HCQ alone or associated with azithromycin;
  • A non-human primate model developed by IDMIT that demonstrated a lack of preventative or curative antiviral efficacy for HCQ.

The data reviewed by the team indicated that chloroquine and hydroxychloroquine likely provide no clinical benefit against COVID-19. The authors of the article proposed thus to move on and explore new options within the strategy of repositioning specific treatments to find new possibilities for COVID-19 therapeutics.

1 : WHO : Public statement for collaboration on COVID-19 vaccine development

 

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