We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Attacking COVID-19 Progression Using Multi-Drug Therapy for Synergetic Target Engagement.
- Authors
Coban, Mathew A.; Morrison, Juliet; Maharjan, Sushila; Hernandez Medina, David Hyram; Li, Wanlu; Zhang, Yu Shrike; Freeman, William D.; Radisky, Evette S.; Le Roch, Karine G.; Weisend, Carla M.; Ebihara, Hideki; Caulfield, Thomas R.
- Abstract
COVID-19 is a devastating respiratory and inflammatory illness caused by a new coronavirus that is rapidly spreading throughout the human population. Over the past 12 months, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has already infected over 160 million (>20% located in United States) and killed more than 3.3 million people around the world (>20% deaths in USA). As we face one of the most challenging times in our recent history, there is an urgent need to identify drug candidates that can attack SARS-CoV-2 on multiple fronts. We have therefore initiated a computational dynamics drug pipeline using molecular modeling, structure simulation, docking and machine learning models to predict the inhibitory activity of several million compounds against two essential SARS-CoV-2 viral proteins and their host protein interactors—S/Ace2, Tmprss2, Cathepsins L and K, and Mpro—to prevent binding, membrane fusion and replication of the virus, respectively. All together, we generated an ensemble of structural conformations that increase high-quality docking outcomes to screen over >6 million compounds including all FDA-approved drugs, drugs under clinical trial (>3000) and an additional >30 million selected chemotypes from fragment libraries. Our results yielded an initial set of 350 high-value compounds from both new and FDA-approved compounds that can now be tested experimentally in appropriate biological model systems. We anticipate that our results will initiate screening campaigns and accelerate the discovery of COVID-19 treatments.
- Subjects
UNITED States. Food &; Drug Administration; COVID-19; MEMBRANE fusion; SARS-CoV-2; COVID-19 treatment; BIOLOGICAL systems; VIRAL proteins; CLINICAL drug trials; ANTIVIRAL agents
- Publication
Biomolecules (2218-273X), 2021, Vol 11, Issue 6, p787
- ISSN
2218-273X
- Publication type
Article
- DOI
10.3390/biom11060787