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COVID-19 represents an unprecedented pandemic posing severe health risks over the entire world population. Millions of people have been infected, and the death toll in some countries surpassed the number from the Spanish Flu.
Committed to discovering fast-track COVID-19 therapeutics, IPK pioneered a drug repositioning strategy using our Biosafety Level 3 facilities to evaluate the efficacy of thousands of approved and proposed drugs including approximately 1,500 US-FDA-approved compounds. IPK’s state-of-the-art high-throughput/high-content 'Phenomic' screening platform enabled accelerated identification of drug candidates that had potent antiviral activities against SARS-CoV-2 in cell-based infection assay experiments. Based on these studies the lead-drug candidates identified: nafamostat, camostat, ciclesonide, and niclosamide, were selected for further development and/or clinical trials.
Our latest studies reveal selected anti-SARS-CoV-2 drug candidates are equally effective against the SARS-CoV-2 variants identified from the UK and South Africa compared to the original SARS-CoV-2 isolates. This promising result provides hope that COVID-19 therapeutics may provide important clinical therapy recourse to emerging variants.
IPK COVID-19 Drug Repositioning
For clinical trials, the Pasteur Network consisting of 33 members located in 25 countries worldwide benefitted IPK’s efforts to initiate international clinical trials for COVID-19 therapeutics. In particular, combined with the support of the Korean and French authorities IPK successfully established a bridge between Korean pharmaceutical companies and international clinical partners convergent on the goal to fast-track COVID-19 therapeutics. Thanks to these efforts, the identified drug candidates are currently undergoing Phase II and III clinical trials in Korea and overseas.
COVID-19 Drug International Clinical Trials
1. Jeon S, et al. Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs. (2020) Antimicrob Agents Chemother. 64(7):e00819-20 (Selected as Editor’s Pick)
2. Ko M, et al. Comparative analysis of antiviral efficacy of FDA-approved drugs against SARS-CoV-2 in human lung cells. (2021) J Med Virol. 93(3);1403-1408.
3. Lee J, et al. TMPRSS2 and RNA-Dependent RNA Polymerase Are Effective Targets of Therapeutic Intervention for Treatment of COVID-19 Caused by SARS-CoV-2 Variants (B.1.1.7 and B.1.351) (2021) Microbiol Spectr. 9(1):e0047221
Institut Pasteur Korea has identified an innovative drug candidate, Q203, which has a novel mechanism of action and is highly effective against both multi-drug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (TB). Q203 has successfully advanced through preclinical testing.
Institut Pasteur Korea’s cell-based phenotypic screening technology, which utilizes a physiologically relevant cellular disease model, enabled the identification of chemical compounds that effectively killed TB in host macrophages and led to development of this first-in-class drug candidate. The results of this work were published in Nature Medicine in August 2013. ( > Press Release)
Q203 was licensed to Qurient Co. Ltd., a spin-off company of Institut Pasteur Korea. An IND submission was filed on this molecule in the US in 2014 for further development toward clinical evaluation.
Institut Pasteur Korea has developed first-in-class drug candidates to effectively treat Hepatitis C.
The well-developed Hepatitis C virus (HCV) program at Institut Pasteur Korea has delivered a highly active lead series that has a novel mechanism of action with therapeutic efficacy against HCV. This molecule interferes with early (post attachment) step of the HCV life cycle by targeting E1. It inhibits infectivity of HCV particles without preventing particle formation or changing particle density. More importantly, this drug candidate prevents virus secretion and inhibits the cell-to-cell spread that is the major route of transmission in the liver. The most advanced lead series has excellent overall properties, including accumulation to target organ, pico- to nano-molar activity against various genotypes (1, 2, 3, 4 & 7) and a good safety profile.
Through successful lead optimization with support from the Korean Drug Development Fund, the molecule has been licensed out to a bio-venture company for further R&D. ( > Press Release)
Institut Pasteur Korea has succeeded in development of new first-in-class drug candidate to overcome antibiotics resistance in collaboration with a bio-venture company in Korea. ( > Press Release)
The joint research team focused on the methicillin resistant staphylococcus aureus (MRSA), which is known to be a major cause of nosocomial infection and found in about 70 percent of patients with staphylococcus aureus infections in hospitals in Korea. The MRSA are known as super bacteria resistant to most antibiotics.
Researchers at Institut Pasteur Korea searched for innovative antibacterial compounds with new mechanisms against MRSA on the basis of basic research conducted on the physiology and resistant mechanisms of bacteria. By analyzing the efficacy of about 100,000 compounds using target-free image-based high throughput screening (HTS) technology, researchers successfully identified a new drug candidate that kill resistant bacteria with new mechanisms of action unknown to date. Notably, the new drug candidate showed efficacy in not only MRSA but also vancomycin-resistant bacteria.
Institut Pasteur Korea succeeded in developing a new concept of a liver cancer drug candidate that can overcome anti-cancer drug resistance and liver toxicity, which are side effects of existing liver cancer treatments. The new drug candidate was licensed out to a bio-venture company in Korea. ( > Press Release)
Based on the fact that anticancer drug resistance and cancer recurrence are caused by tumor stem cells, the researchers of Institut Pasteur Korea established an innovative compound efficacy evaluation system based on a new concept of mixed culture model. Applying the mixed culture model to the image-based high throughput screening (Phenomic Screen) to test efficacy of compounds, researchers successfully developed a new drug candidate that specifically kills tumor cells and tumor stem cells.
The mixed culture model is unique as it is mimicking the actual in vivo liver tissue where various substrate cells, immune cells, liver cancer cells, liver cancer stem cells, and normal liver cells are mixed. Leveraging this new approach, not only the anti-cancer effects of compounds but also the liver toxicity of normal cells was analyzed at once, enabling researchers to identify the novel drug candidates with excellent anti-cancer efficacy and low hepatotoxicity.
Institut Pasteur Korea identified a flavanone derivative-based drug candidate with therapeutic efficacy against fibrosis through collaborative research and licensed it out to domestic company. ( > Press Release)
Researchers of Institut Pasteur Korea screened the in-house library of natural products and natural product derivatives utilizing its core image-based drug screening technology and identified that flavanone derivative carries excellent anti-fibrotic properties. Flavanones are abundantly contained in the peel of citrus fruits. In particular, the research team constructed a “3D multicellular liver spheroid” model consisting of hepatocytes, surrounding blood vessels, immune cells, signaling molecules, and extracellular matrix to mimic conditions inside the human body. Integration of the innovative model to drug screening led to discovery of a drug candidate with significant preclinical efficacy.