Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation
| Autor: | Angela Serra, Michele Fratello, Antonio Federico, Ravi Ojha, Riccardo Provenzani, Ervin Tasnadi, Luca Cattelani, Giusy del Giudice, Pia A S Kinaret, Laura A Saarimäki, Alisa Pavel, Suvi Kuivanen, Vincenzo Cerullo, Olli Vapalahti, Peter Horvath, Antonio Di Lieto, Jari Yli-Kauhaluoma, Giuseppe Balistreri, Dario Greco |
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| Přispěvatelé: | Tampere University, BioMediTech, Department of Virology, Division of Pharmaceutical Chemistry and Technology, Medicum, Viral Zoonosis Research Unit, Drug Research Program, ImmunoViroTherapy Lab, Division of Pharmaceutical Biosciences, Helsinki One Health (HOH), HUSLAB, Veterinary Microbiology and Epidemiology, Veterinary Biosciences, Olli Pekka Vapalahti / Principal Investigator, Institute for Molecular Medicine Finland, Divisions of Faculty of Pharmacy, Jari Yli-Kauhaluoma / Principal Investigator, Pharmaceutical Design and Discovery group, Helsinki Institute of Sustainability Science (HELSUS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
EXPRESSION
UCN-01 GENES delta variant AcademicSubjects/SCI01060 drug design Drug Evaluation Preclinical 7-hydroxystaurosporine Antiviral Agents Giant Cells kinase inhibitors Humans syncytia Molecular Biology Case Study SARS-CoV-2 SET ENRICHMENT ANALYSIS Drug Repositioning COVID-19 Computational Biology KINASE INHIBITOR IN-VITRO bafetinib 113 Computer and information sciences virtual screening Staurosporine COVID-19 Drug Treatment Pyrimidines 317 Pharmacy A549 Cells 3121 General medicine internal medicine and other clinical medicine DISCOVERY 3111 Biomedicine Information Systems PACKAGE |
| Zdroj: | Briefings in Bioinformatics |
| ISSN: | 1477-4054 1467-5463 |
| Popis: | The pharmacological arsenal against the COVID-19 pandemic is largely based on generic anti-inflammatory strategies or poorly scalable solutions. Moreover, as the ongoing vaccination campaign is rolling slower than wished, affordable and effective therapeutics are needed. To this end, there is increasing attention toward computational methods for drug repositioning and de novo drug design. Here, multiple data-driven computational approaches are systematically integrated to perform a virtual screening and prioritize candidate drugs for the treatment of COVID-19. From the list of prioritized drugs, a subset of representative candidates to test in human cells is selected. Two compounds, 7-hydroxystaurosporine and bafetinib, show synergistic antiviral effects in vitro and strongly inhibit viral-induced syncytia formation. Moreover, since existing drug repositioning methods provide limited usable information for de novo drug design, the relevant chemical substructures of the identified drugs are extracted to provide a chemical vocabulary that may help to design new effective drugs. |
| Databáze: | OpenAIRE |
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