Creation date in repository: 2022-02-03
Abstract: El SARS-CoV-2 és el virus responsable de la pandèmia de la COVID-19. Aquest treball pretén reposicionar els fàrmacs aprovats com a inhibidors putatius d'una diana amb un paper fonamental en la replicació del virus: la proteasa principal (M-pro). Aquí, es va aplicar una estratègia de cribratge virtual (VS) basada en l'acoblament de consens original. L'acoblament es va realitzar amb tres programes –Glide, FRED i AutoDock Vina– i només els modes d'unió d'alta afinitat equivalents predits per tots ells es van considerar posicions bioactives. Es van predir set possibles inhibidors del SARS-CoV-2 M-pro: Perampanel, Carprofen, Celecoxib, Alprazolam, Trovafloxacin, Serafloxacin i Etil biscumacetat. Quatre d'ells han mostrat bioactivitat in vitro. SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. This work aims to reposition approved drugs as putative inhibitors of a target with a pivotal role in the replication of the virus: the main protease (M-pro). Here, an original consensus docking-based virtual screening (VS) strategy was applied. Docking was performed with three programs –Glide, FRED and AutoDock Vina– and only the equivalent high affinity binding modes predicted by all of them were considered bioactive poses. Seven possible SARS-CoV-2 M-pro inhibitors were predicted: Perampanel, Carprofen, Celecoxib, Alprazolam, Trovafloxacin, Serafloxacin and Ethyl biscoumacetate. Four of them have shown in vitro bioactivity.
Subject: Bioquímica i biotecnologia
Language: en
Subject areas: Bioquímica i biotecnologia Biochemistry and biotechnology Bioquímica y biotecnología
Department: Bioquímica i Biotecnologia
Student: Mestres Truyol, Júlia
Academic year: 2020-2021
Title in different languages: Inhibició de la proteasa principal del SARS-CoV-2 (M-pro): reposicionament de set fàrmacs aprovats mitjançant un cribratge virtual basat en docking consens Targeting SARS-CoV-2 main protease (M-pro): repositioning of seven approved drugs in a consensus docking-based virtual screening Inhibición de la proteasa principal del SARS-CoV-2 (M-pro): reposicionamiento de siete fármacos aprobados mediante un cribado virtual basado en docking consenso
Work's public defense date: 2021-06-23
Access rights: info:eu-repo/semantics/openAccess
Keywords: COVID-19; SARS-CoV-2; M-Pro; 3CL-pro; cribratge virtual; docking proteïna-lligand COVID-19; SARS-CoV-2; M-Pro; 3CL-pro; virtual screening; protein-ligand docking COVID-19; SARS-CoV-2; M-Pro; 3CL-pro; cribado virtual; docking proteína-ligando
Confidenciality: No
Title in original language: Targeting SARS-CoV-2 main protease (M-pro): repositioning of seven approved drugs in a consensus docking-based virtual screening
Project director: Pujadas Anguiano, Gerard
Education area(s): Biotecnologia
Entity: Universitat Rovira i Virgili (URV)
Repositori URV