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Institut Pasteur Korea Held a Satellite Session at 2021 KSBMB

2021-06-04

Institut Pasteur Korea Held a Satellite Session
at 2021 KSBMB

Institut Pasteur Korea (IPK) held a Satellite Session at the 2021 Society of Biochemical and Molecular Biology (KSBMB) took place at BEXCO and online last week. The IPK Satellite Session, titled “Emerging Opportunities for Drug Discovery on Infectious Diseases,” led to meaningful discussions among the domestic and international experts of infectious diseases that filled the room with commitments to prepare and respond to a pandemic.

The session chaired by Dr. Youngmee Jee, CEO of IPK, and Dr. Inhee Choi, Head of Medicinal Chemistry of IPK, addressed the unmet global need in infectious diseases, including COVID-19, neglected diseases, antimicrobial resistance, and RNA virus infections. Four qualified global experts, including Dr. Charles Mowbray, Discovery Director of DNDi, Dr. Laura JV Piddock, a Professor of Microbiology of Univ. Birmingham UK and GARDP Scientific Director, Dr. Seungtaek Kim, Head of Zoonotic Virus Laboratory of Institut Pasteur Korea, and Dr. Lak Shin Jeong, Professor of Seoul National University, shared the latest research activities and insights with the audiences.

Here is the abstract of each speaker:

1. Drug Discovery for NTDs and Global Pandemics (Dr. Charles Mowbray)

The Drugs for Neglected Diseases initiative (DNDi) exists to serve the needs of neglected patients suffering from neglected tropical and infectious diseases and has already successfully delivered 8 new treatments impacting millions of lives. We have also developed considerable experience in applying our model of collaborative, virtual drug discovery working with our partners across the globe and have assembled a portfolio of projects which may lead to further new treatments. This approach will be described and illustrated with examples for Chagas disease and leishmaniasis and newer applications for COVID-19 and AMR.

2. GARDP: filling gaps in the new antibiotic pipeline (Professor Laura JV Piddock)
The number of drug-resistant infections is outpacing the provision of new antibacterial treatments and causing an increase in human morbidity and mortality. This is a global problem and impacts the health of everyone and economies of countries around the world. Those most affected are babies, children, the elderly, immunocompromised, and those in countries with weak health systems. GARDP’s mission is to focus on developing new treatments, safeguarding their responsible use, and ensuring sustainable access. GARDP’s activities are on (1) priority populations (newborn babies, children, hospitalized adults impacted by AMR, vulnerable and marginalized populations), (2) WHO critical and high priorities for which new treatments are needed, and (3) priority infections/syndromes (serious bacterial infections, neonatal sepsis, and sexually transmitted infections). GARDP’s Research and Development priorities are the clinical and pharmaceutical development of antibiotics and driving sustainable access. GARDP will also fill gaps in the discovery and exploratory research pipeline by working where others are not (e.g., screening of novel libraries, new chemical entities for underexploited targets). GARDP is building a public health-oriented portfolio to deliver its 5 BY 25 goal (5 new treatments by 2025). GARDP’s pipeline portfolio includes of new and old antibiotics with several under evaluation or development. This presentation will describe the scientific aspects of GARDP’s work.

3. Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs (Dr. Seungtaek Kim)
COVID-19 is an emerging infectious disease and was declared as a pandemic by WHO. Currently, there is no effective therapeutic available for this disease. Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. We found a total of 24 drugs which exhibited antiviral efficacy (0.1 µM < IC50 < 10 µM) against SARS-CoV-2. Among them, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects. Using Calu-3 human lung cell line, we also compared antiviral efficacy of the drug candidates and found nafamostat is the most potent antiviral therapeutic option. In the near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19.

4. Development of Anti-RNA Virus Nucleosides (Professor Lak Shin Jeong)
RNA viruses are often highlighted as the most common class of pathogens behind new human diseases, with the rate of 2 to 3 new viruses being identified each year such as ongoing outbreak of coronavirus disease 2019 (COVID-19). Over the past years, outbreaks of a number of emerging positive-stranded RNA (+RNA) viruses, such as the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), Chikungunya virus (CHIKV), and Zika virus (ZIKV) have seriously threatened human health. However, antiviral therapy is still lacking for most of these viruses. Thus, it is desirable to develop new antiviral agents for the treatment of viral diseases caused by RNA viruses.
Nucleos(t)ide analogues have a long history in the development antiviral therapeutic agents. A variety of carbocyclic adenosine analogues with antiviral activity, including naturally occurring aristeromycin and neplanocin A are assumed to exert their antiviral action via the inhibition of cellular S-adenosylhomocysteine (SAH) hydrolase. Therefore, SAH hydrolase has been recognized as potential pharmacological target for the development of new antiviral agents. Although neplanocin A and aristeromycin act as potent inhibitors of SAH hydrolase, their therapeutic utility is limited, because of their significant toxicity. Thus, in search of less toxic and more potent inhibitor of SAH hydrolase, the 6′-fluorinated aristeromycin and 6′-fluorinated-5′-homo-aristeromycin were designed, synthesized and evaluated for their antiviral activity against various RNA viruses. Among these, 6′,6′-difluoro-aristeromycin exhibits potent antiviral activities against COVID-19, MERS-CoV, SARS-CoV, ZIKV, and CHIKV. In addition, 6′-β-fluoro-homo-aristeromycin showed potent antiviral activity (EC50 = 0.12 μM) against the CHIKV, without noticeable cytotoxicity up to 250 μM. It was identified that the introduction of a fluorine at the 6′-position enhanced the inhibition of SAH hydrolase and the activity against RNA viruses. Design, synthesis and antiviral data of carbocyclic nucleosides will be presented in detail.

* The session was held under strict compliance with the COVID-19 quarantine regulations.

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