HANNOVER, Germany, May 7, 2020 /PRNewswire/ -- The new coronavirus SARS-CoV-2 has triggered a public health emergency of international concern. To date, there is neither a vaccine nor drugs for COVID-19 treatment available. Researchers of the international consortium iCAIR® [https://www.item.fraunhofer.de/en/lighthouse-projects/icair-project.html] are striving to develop novel anti-infective agents to treat or prevent clinically significant respiratory diseases caused by viruses, fungi and bacteria - and recently started a project to develop medications against SARS-CoV-2.
In the iCAIR® consortium (Fraunhofer International Consortium for Anti-Infective Research) Fraunhofer ITEM [https://www.item.fraunhofer.de/en.html] is collaborating with Griffith University's Institute for Glycomics [https://www.griffith.edu.au/institute-glycomics/about-us/centres-of-excellence/fraunhofer-institute] (IfG) in Australia, the Hannover Medical School [https://www.mhh.de/en/] (MHH; Germany), and TWINCORE [https://www.twincore.de/en/home/], a joint venture between MHH and Helmholtz Centre for Infection Research [https://www.helmholtz-hzi.de/en/] (Germany) to develop new, urgently needed agents against respiratory tract infections. "Striving to develop a drug for COVID-19 treatment, we combine our complementary expertise and pool a broad spectrum of methods in this research alliance - from the identification of therapeutic targets and drug candidates via drug design and efficacy testing in preclinical models to toxicological studies," says Professor Armin Braun, Fraunhofer ITEM Division Director of Preclinical Pharmacology and Toxicology and coordinator of the iCAIR® consortium.
The researchers are first screening substance libraries for drug candidates that stop SARS-CoV-2 infection. "We made use of substance libraries available at IfG and HZI. Furthermore, Fraunhofer IME with its ScreeningPort [https://www.ime.fraunhofer.de/en/Research_Divisions/business_fields_TM/screeningport.html] in Hamburg and expertise in drug discovery based on high-throughput technology is involved," explains Braun.
Identified drug candidates will be subject to chemical modification to optimize their efficacy and safety. Efficacy and tolerability testing will be performed in sophisticated cell-based infection models and human precision-cut lung slices (PCLS [https://www.item.fraunhofer.de/en/focuses-of-research/drugdevelopment/PCLS.html]). This viable, immunocompetent lung tissue model enables detailed analysis of biological and immunological responses to the virus in the deep lung - which is where the SARS-CoV-2 infection is most harmful. A unique human test system is thus available for safety and efficacy testing of novel medications.
"We will systematically develop the most promising candidates further to achieve inhaled administration, as SARS-CoV-2 primarily infects the lungs and airways," explains Braun. "Administering therapeutics via the airways enables high local concentrations at the site of infection, reducing the required doses of active substance. In addition, systemic side effects can be minimized." Fraunhofer ITEM experts will test the drug candidates selected for inhaled administration in an in-house developed and patented in-vitro exposure system - P.R.I.T.® ExpoCube® [https://www.item.fraunhofer.de/en/services-expertise/drug-development/preclinical-testing.html]. This system allows inhaled administration of the drug candidates into the lung to be mimicked by using human airway epithelial cells or PCLS. Potential local cytotoxic effects can thus be ruled out and the best candidates for further preclinical development can be identified.
"The iCAIR® consortium is ambitious: together, we want to expedite the advancement of new drugs into the preclinical phase. Unfortunately, there is still a significant gap between the discovery of new agents and their further development into usable therapeutics, which we have to bridge even faster now with our combined synergies to curtail the COVID-19 pandemic," says Professor Mark von Itzstein, IfG Director and iCAIR® project manager in Australia.
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