The SARS-CoV-2 outbreak, which started in Dec. 2019, has so far not been contained due to unpreparedness and unsuccessful development of antiviral drugs against SARS-CoV-2. In response to this pandemic, we propose strategies for the development of novel antiviral agents against a number of known viral targets using in-silico modeling and laboratory testing to rapidly identify and validate their efficiency in blocking viral functions. We have prior experience working with viruses of the same family, which include those that cause Porcine epidemic diarrhea (PEDv) and influenza A/H1N1, and aim to -build small molecules to block the new virus. The goal of our design will be to find molecules for 1) the inhibition of SARS-CoV-2 replication; 2) blocking of S protein-ACE2-mediated viral entry; 3) targeting SARS-CoV protease (3CL); 4) inhibiting viral protein nsp-14 – DDX1 helicase interaction. Each molecule will be evaluated for specificity and efficacy in in-vitro assays. We will synthesize target proteins and promising compounds and test their interactions by functional assays, including cell toxicity, and biophysical assays including analytical ultracentrifugation (AUC), Microscale Thermophoresis (MST), and by high throughput screening.
Trushar Patel;Neal Davies;Borries Demeler
Maulik Badmalia;Siddhartha Biswas;Dong Ju Kim;Amy Henrickson
Applied Pharmaceutical Innovation
Biochemistry / Molecular biology
Professional, scientific and technical services
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