Together we stand! Coordinating international efforts seeking drugs to fight COVID-19

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By Wang-Shick Ryu (Institut Pasteur Korea), Spencer L Shorte (Institut Pasteur International Network), Amadou Sall (Institut Pasteur Dakar)

Behind COVID-19 the culprit is SARS-CoV-2 a human coronavirus closely related to the strain causing the 2003 SARS outbreak. However, unlike SARS, COVID-19 has not remained regionally confined. Instead, it exploded into a pandemic. As of today, over 27 million people worldwide have been infected and among them, over 870,000 infected people died. What is daunting is that even after these considerable casualties, we remain unable to predict when or how the COVID-19 pandemic might be brought under control. In the absence of vaccine, or adequate drug therapy the only recourse remains a combination of physical barrier-protection, social distancing, and personal hygiene. Therein rapid and reliable diagnostics combined with contact-tracing allow public-health authorities to map the epidemiology of the contagion spread, and at least try to implement policies aiming to avoid overwhelming domestic health services.

In face of the continued pandemic there is urgent need for vaccines and antivirals. Consequently, the magnitude of the shift in global R&D resources toward vaccine and drug development since the pandemic is truly unprecedented. Development is further facilitated by authorities either lifting or simplifying regulatory approval steps. Thanks to these changes, already two-dozen vaccines are at phase 2/3 clinical trial. By comparison, progress toward clinical approval for drugs with high-efficacy capable to assure beneficial outcome for COVID-19 patients has been relatively modest.

Typically, new drug development takes more than 10 years from basic-science “benchtop” discovery to approved clinical “bedside” medication. Further, this slow process is unfortunately failure-prone, often due to safety considerations. Mitigating these issues, an alternative approach has recently emerged based on the somewhat counter-intuitive premise that drugs proven for one disease indication, also have unanticipated beneficial effects for other disease indications. So-called: drug-repurposing obviates or greatly diminishes the need for phase I safety and toxicity studies, and appears especially relevant to infectious disease. Repurposing allows restricting screening to only drugs already tested and accepted as generally safe for human-use. In the face of emerging infectious diseases like COVID-19 Institut Pasteur Korea (IPK) has combined drug-repurposing with highly sensitive in vitro cell-based assays capable to screen drugs for SARS-CoV-2 antiviral properties. Thus, screening several thousand bioactive small molecules, including 1500 FDA approved drugs, IPK found over 20 drugs that inhibit SARS-CoV-2 infection. Based upon consideration of drug properties, generic availability, and bulk manufacturing costs important to downstream equitable availability and global distribution, IPK identified four optimal drug candidates to proceed to clinical trials to test for COVID-19 therapeutic efficacy: ciclesonide, niclosamide, nafamostat, and camostat.

Coordinating clinical trials internationally is challenging inasmuch as clinical protocols and parameters must correspond in a manner satisfying the requirements of multiple drug and ethics approval authorities in different countries. Evidently, there is no established governance in this context. Bolstered by our robust partnership among the 32 member institutes of the Institut Pasteur International Network (IPIN) an international consortium was forged by coordination among the government authorities of the Rep. of Korea, France, and the Rep. of Senegal, drug-manufacturing industry, clinicians and research organizations. In collaboration with Institut Pasteur Dakar (IPD) and the pharmaceutical company in the Rep. of Korea (CKD Pharma) our first clinical trial to establish the therapeutic efficacy of nafamostat was established. Led by the success of this effort other countries are stepping up similarly to join the same consortium initiative catalyzing COVID-19 drug-repurposing trials in countries including: Mexico, Brazil, and Australia.

Joint international efforts to accelerate global manufacturing and availability of low-cost generically available drugs against COVID-19 is an historic challenge. The Korea-Senegal model described here illustrates how established grass-roots scientific research networks like IPIN can effectively foster international cross-border collaboration. In the context of the Paris Peace Forum we conclude that common vision and shared humanitarian values are a powerful fabric that will be necessary to binding the diverse interests most likely to yield a truly global panacea to end the COVID-19 crisis.

Views expressed in this publication are the author’s and do not necessarily reflect the views of the Paris Peace Forum.

Dr. Wang-Shick Ryu is the CEO of Institut Pasteur Korea and a world renowned virologist. Leading a research institute focused on infectious diseases, Dr. Ryu has been at the forefront in capitalizing on basic science to drug discovery with the aim of responding to the emerging global threats, such as coronavirus, Zika virus, hepatitis virus, and super bacteria. Currently, he is also faculty at Yonsei University, a prestigious university in the Rep. of Korea.

He received his doctoral degree in molecular virology from the University of Wisconsin-Madison. He is an author of over 50 research articles, and also an author of a textbook <Molecular Virology>. He shares his knowledge and expertise by serving as a board member and/or scientific editor in many international journals, including Journal of Virology and Antimicrobial Agents and Chemotherapy.

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