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The group of Dr. Mar Siles Lucas at IRNASA handles in vitro and in vivo models of parasitic-host interactions with Fasciola hepatica, which could be used to evaluate the potential of the parasite and its molecules to modulate relevant entry routes and inflammation routes in COVID-19. On one hand, this parasite has shown influence on the expression of endocytosis-related molecules (e.g. clathrins) on in vitro mouse epithelial cells, routes that may be relevant for SARS-Cov-2 entry to human cells. In addition, F. hepatica results in a modified Th2 response without the inflammatory component in its host in vivo, and this modulation may result in a controlled inflammatory response to COVID-19.
This collaboration will employ a multi-disciplinary approach to identify inhibitors of SARS-CoV-2 receptor binding and entry. Combining expertise in medicinal chemistry, computational chemical biology, structural biology, and virology, 3 parallel approaches will be employed: (1) Immediate testing of compound libraries (>1,400) using a high-throughput cell assay for SARS-CoV-2 receptor binding and entry. (2) Computational screening and design, synthesis, and evaluation (3). Development of protein-based inhibitors derived from the ACE2 receptor. The final evaluation of hits for effectiveness and drug resistance will be done with SARS-CoV-2.
The project proposes a new strategy for the screening of drugs and antibodies against the SARS-CoV-2 coronavirus. This is an innovative technology for drug screening that uses an affordable, fast, safe and efficient system to evaluate all types of antiviral compounds and antibodies that block the entry of SARS-CoV-2 virus into human cells. The use of recombinant viruses has been successfully used in drug screening for various medically important viruses, as well as in serological screening. The advantages of the proposal are well founded, highlighting that this technology may be applicable in the future to other viruses that constitute an emerging public health problem.
The main goal of this project is to define the effect of all possible mutations in a viral capsid, and to understand how different cellular and environmental pressures can alter the viability of such mutations in the capsid.