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COVID-19 Repurposed Therapeutics Targeting the Viral Protease and Spike-protein:ACE2 Interface using MD-based Pharmacophore and Consensus Virtual Screening

preprint
submitted on 07.05.2020 and posted on 08.05.2020 by brady garabato, Federico Falchi, Andrea Cavalli

Molecular dynamics (MD) and enhanced sampling MD was performed for 100 ns on the biological assembly of the COVID-19 protease (6LU7), and a template of the COVID-19 S-protein:ACE2 receptor interface (99.88% coverage of 6M0J; model03, swissmodel). Apo-site pharmacophores of the resulting structural clusters were used to mine the FDA database (8700 compounds), and a multi-target library was developed from MD-based hits in high affinity sites across 100 ns. Consensus hits from high throughput docking in crystal structures 5R82, 6LU7 and 6Y2F (protease), and 6VW1 (S-protein:ACE2) were also added, and the resulting libraries were re-docked into MD sites to collect potential COVID-19 re-purposed therapeutics by estimated binding energies.

History

Email Address of Submitting Author

brady.garabato@iit.it

Institution

Istituto Italiano di Tecnologia (IIT)

Country

Italy

ORCID For Submitting Author

0000-0002-1180-3824

Declaration of Conflict of Interest

None

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