Scientists in the University of Florida College of Pharmacy have joined a European research network that aims to develop broad-spectrum antiviral drugs to combat the next global pandemic.
Hendrik Luesch, Ph.D., a professor and chair of medicinal chemistry and the Debbie and Sylvia DeSantis Chair in Natural Products Drug Discovery and Development in the UF College of Pharmacy, is a co-principal investigator in the newly established VIGILANT research network. The program brings together experts in biochemistry, medicinal chemistry, virology and molecular and cell biology to develop compounds with broad antiviral activity that could limit the spread of a virus in the early stages of a pandemic.
“Vaccines are an essential part of the fight against pandemics, but they are only available months after an outbreak,” Luesch said. “Instead of playing catch-up and developing antivirals and vaccines against the specific virus once the genomic sequence becomes available, we aim to develop host-directed therapeutics that can be effective against any emerging virus on day one of a pandemic. These agents target human proteins essential for virus replication and are hijacked by viruses.”
Emerging viruses, such as those responsible for the COVID-19 pandemic and the Ebola epidemic, pose a serious threat to global health and economic stability.
To better combat future viral pandemics, Luesch said it is essential to have drugs with broad antiviral activity that can be used immediately without prior knowledge of the specific pathogen. Such drugs, when deployed immediately, reduce the spread of the pathogen and may prevent a local outbreak from developing into a global pandemic. At the same time, they could be used as a therapy to help infected patients avoid serious disease, reducing the burden on health care systems.
“During the COVID-19 pandemic, we assembled a dream team of scientists in the U.S. and Europe and characterized a new mechanism of action to combat SARS-CoV-2 to develop host-directed therapeutics with broad-spectrum antiviral activity based on one of our marine-derived natural products, which prevents the production and functional viral glycoproteins and inhibits viral replication,” said Luesch. “Our work caught the attention of a European consortium, as our lead compound showed potent cellular activity against coronaviruses, Influenza A and potentially other viruses of pandemic concern.”
Luesch’s team is now working on an additional target critical for viral glycoprotein activation and has already identified ultrapotent inhibitors from the ocean.
UF researchers will scale up the production of two lead compounds against the two host targets and perform medicinal chemistry campaigns to improve their antiviral activity against several viruses. Luesch’s team will collaborate on the rigorous in vitro and in vivo evaluation with 11 European Union participants from seven institutions in Germany, Sweden, Finland, Slovenia and the Netherlands, with the mission to advance pandemic preparedness and develop new antivirals targeting the transport of viral envelope proteins into the endoplasmic reticulum of infected cells as well as their activation by host cell proteases.
The National Institute of Allergy and Infectious Diseases within the National Institutes of Health is an associate partner.
“We need science beyond borders and teamwork across continents to address global health threats,” Luesch said. “Working with the VIGILANT research network will improve our preparedness for future pandemics.”
Backed by a €7.5 million award from the European Union, the VIGILANT research network is coordinated by the German Primate Centre – Leibniz Institute for Primate Research. UF will play a key role in the initiative, receiving about $600,000 over four years. Other participants are from the Philipps University of Marburg (Germany), Friedrich Loeffler Institute (Germany), Karolinska Institute (Sweden), Lund University (Sweden), University of Helsinki (Finland), Jozef Stefan Institute (Slovenia) and Hubrecht Institute (Netherlands).
UF faculty collaborating with Luesch on the project include Research Associate Professors of Medicinal Chemistry Qi-Yin Chen, Ph.D., Ranjala Ratnayake, Ph.D., and Gustavo Seabra, Ph.D.