I’m passionate about studying virus-host interactions with the goal of identifying new antiviral targets that can be exploited for antiviral drug development, which the world is in clear need of. In the past 20 years, we have experienced four zoonotic outbreaks of respiratory viruses causing global distress: SARS in 2002-2003, H1N1 swine flu in 2009, MERS in 2012 and the current COVID-19 pandemic caused by SARS-CoV-2. Two burning research topics are evident from this: (a) the necessity to fully understand how these zoonotic viruses adapt to the human respiratory tract and (b) the requirement to develop broad therapeutic concepts covering distinct respiratory virus families.
One of my research focuses is the protease dependency of influenza -and coronaviruses. Cleavage of their viral surface protein (hemagglutinin in case of influenza and spike in case of coronavirus) is a prerequisite for viral entry. I investigate which airway proteases are involved in this activation, how these viruses evolve to better replicate in the respiratory tract and how this impacts transmission. These insights are crucial for developing host-targeting drugs that prevent virus activation. Such inhibitors hold a promise for a broad-spectrum treatment of respiratory viruses sharing commonalities in protease dependency.
Laporte M., Raeymaekers V., Van Berwaer R., Vandeput J., Marchand-Casas I., Thibaut H.-J., Van Looveren D., Martens K., Hoffmann M., Maes P., Pöhlmann S., Naesens L., Stevaert A. The SARS-CoV-2 and other human coronavirus spike proteins are fine-tuned towards temperature and proteases of the human airways. PLOS Pathogens, 2021, DOI: 10.1371/journal.ppat.1009500
Laporte M., Raeymaekers V., Boogaerts T., Nehlmeier I., Chiu W., Benkheil M., Vanaudenaerde B., Stevaert A., Pöhlmann S., Naesens L.. Hemagglutinin cleavability, acid-stability and temperature dependence optimize influenza B virus for replication in human airways. Journal of Virology, 2019. DOI: 10.1128/JVI.01430-19
Laporte M., Naesens L. Airway proteases: an emerging drug target for influenza and other respiratory virus infections. Current Opinion in Virology, 2017. 24:16-24. DOI: 10.1016/j.coviro.2017.03.018
de Castro, S., Ginex, T., Vanderlinden, E., Laporte, M., Stevaert, A., Cumella, J., Gago, F., Camarasa, M. J., Luque, F. J., Naesens, L. & Velazquez, S. N-benzyl 4,4-disubstituted piperidines as a potent class of influenza H1N1 virus inhibitors showing a novel mechanism of hemagglutinin fusion peptide interaction. European Journal of Medicinal Chemistry, 2020. 194, 112223. https://doi.org/10.1016/j.ejmech.2020.112223