PhD defence
Antiviral strategies against emerging coronaviruses
- C. Salgado Benvindo da Silva
- Date
- Friday 20 September 2024
- Time
- Location
-
Academy Building
Rapenburg 73
2311 GJ Leiden
Supervisor(s)
- Prof.dr. E. J. Snijder
- dr. M. J. van Hemert
Summary
RNA viruses, including those from the Coronaviridae family, are the etiological agents responsible numerous epidemics and pandemics. SARS-CoV-2, first detected at the end of 2019, infected over 770 million people over the following 4 years, according to official numbers, and continues to evolve and give rise to numerous variants.
This thesis outlines the efforts to contribute to the SARS-CoV-2 antiviral field, initiated at the onset of the COVID-19 pandemic. In here we detail the establishment and characterization of the H1299/ACE2 cell line, engineered to express high levels of the Angiotensin-Converting Enzyme 2 (ACE2) receptor, which is used by SARS-CoV-2 for entry into the host cell. These newly generated cells are highly susceptible to SARS-CoV-2 infection and offer significant advantages over other existing cell lines. Concurrently, our early efforts in repurposed compound screening identified several hit molecules with antiviral activity against SARS-CoV-2, including suramin and honokiol. The antiparasitic drug Suramin inhibits SARS-CoV-2 replication in monkey Vero E6 cells, human Calu-3 cells and in a primary human airway epithelial cell culture model by inhibiting early steps of the replication cycle, most likely virus binding and/or entry. Honokiol, a small molecule extracted from magnolia trees, inhibits SARS-CoV-2 replication in Vero E6 cells and in human A549 cells by acting on a post-entry step of the replication cycle, most likely by modulation of host signaling pathways. Both compounds efficiently inhibited SARS-CoV-2 replication with 50% effective concentration values well below the achievable maximum plasma levels in animal models or humans. Altogether, the advances described in this thesis promise to significantly contribute to the antiviral field, by providing a new practical and robust cell model system for antiviral and virus-host interaction studies, and by characterizing new potential antiviral drugs, which are essential to enhance our understanding of this virus and to better prepare against future (corona)virus outbreaks.
PhD dissertations
Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.
Press enquiries (journalists only)
General information
Beadle's Office
pedel@bb.leidenuniv.nl
+31 71 527 7211