Trump calls anti-malaria drug a ‘gamechanger’ for coronavirus, but the FDA says it needs study – Washington Post Headline 19March2020
Scientists in China describe work on the antimalarial drug chloroquine and report its efficacy against SARS-CoV-2 in vitro in their peer-reviewed publication in Clinical Infectious Diseases earlier this month. Now, investigators in the United States have posted observations that “recent guidelines from South Korea and China report that chloroquine is an effective antiviral therapeutic treatment against Coronavirus Disease 2019.” This latter work, yet to be peer-reviewed, was posted as a google community document for the purpose of rapid communication, with a call for next steps from the scientific community to:
- Disseminate this publication amongst the medical community. Get more feedback.
- Send this publication to your scientific contacts in South Korea and China – let’s get more data, details, etc. Science never ends.
- Translate this paper into all languages.
- Explore all options for use of chloroquine against any medical condition that depends on the turnover of worn out or incorrectly synthesized proteins
Eurofins Discovery Phenotypic Center of Excellence is contributing to this dialogue by sharing data from our BioMAP® Reference Database of over 4,500 compounds profiled in our in vitro human cell-based disease models. The BioMAP Platform and the Diversity PLUS® Panel were built out of a need for more biologically relevant in vitro models of human disease. The phenotypic platform technology is used by leaders in the pharmaceutical industry to gain greater insights on their candidate compounds, from discovery to preclinical efficacy and safety.
BioMAP Diversity PLUS systems are comprised of human primary cell-based assays modeling complex tissue and disease biology of organs (vasculature, immune system, skin, lung) and general tissue biology. Phenotypic profiling in the BioMAP Diversity PLUS Panel evaluates the biological impact of approved drugs and experimental compounds in conditions that preserve crosstalk and feedback mechanisms relevant to human outcomes. The readouts from BioMAP Diversity PLUS assays are increases or decreases in 148 protein-based translational biomarkers (listed across the x-axis in the figure below), annotated when meeting statistical significance relevant to appropriate controls.
Each BioMAP profile represents a characteristic signature that can be compared to other profiles for mechanistic insights.
Both hydroxychloroquinine sulfate and chloroquine phosphate have been profiled in the BioMAP Diversity PLUS Panel; their phenotypic profiles, or signatures (below), are included in the BioMAP Reference Benchmark Database (a partial list of benchmark compounds whose profiles are used for comparative and machine learning purposes is here). Comparative overlay analysis of their biomarker profile plots (chloroquine phosphate at 30 µM and hydroxychloroquinine sulfate at 33 µM) reveals a similar pattern of translational biomarker activities. At these concentrations, neither drug has detectable cytotoxicity. Statistical comparison of the two profile plots yields a Pearson’s correlation coefficient of r = 0.89, above the determined BioMAP threshold for mechanistic similarity.
The drugs have 15 shared activities, including antiproliferative effects on B cells and fibroblasts. Both drugs inhibit immune response biomarkers (decreased immune cytokines sIL-17A, sIL-17F, and sIL-6) and inflammatory biomarkers (decreased VCAM-1 and sTNFα), consistent with drugs approved for treating autoimmune indications.
Interestingly, both hydroxychloroquinine sulfate and chloroquine phosphate modulate disease-relevant biomarkers in the lung system modeling fibrosis-related matrix deposition (MyoF) and the fibroblast system modeling wound-healing related inflammation and tissue remodeling biology (HDF3CGF). Hallmark biomarkers of fibrosis (αSMA, myofibroblast activation, fibrillar collagens, PAI-1) are decreased by both drugs, whereas biomarkers known to be involved in extracellular matrix integrity and remodeling (collagen IV, MMP-1) are increased in these phenotypic profiles. Decreased matrix proteins and increased proteinases are activities consistent with hindered extracellular matrix deposition as well as fibrotic scar formation.
Together these profiles reveal human response biomarkers and mechanistic fingerprints for agents emerging as key therapeutics in the fight against SARS-CoV-2 infections.
According to the Washington Post, FDA Commissioner Stephen Hahn, speaking after the president, said “the FDA is considering giving chloroquine to larger populations of coronavirus patients as part of an “expanded use” testing program. Such a trial in patients would allow the FDA to collect data to measure scientifically whether it works. It was not immediately clear how long it would take the FDA to design the study and get it working at trial sites around the country.”
Eurofins Discovery hopes the information presented here is useful to the scientific community and that by releasing this data we contribute to the rapid response to this outbreak. Eurofins Scientific currently contributes to SARS-CoV-2 testing worldwide.
Alison O’Mahony, PhD and Sheryl P Denker, PhD contributed equally to this post.