Drug repurposing against main protease and RNA-dependent RNA polymerase of SARS-CoV-2 using molecular docking, MM-GBSA calculations and molecular dynamics.
Ahmed O MohammedMazin I Abo-IdreesAlaa A MakkiWalaa IbraheemAbdulrahim Altoam AlzainPublished in: Structural chemistry (2022)
A virus called severe acute respiratory distress syndrome coronavirus type 2 (SARS-CoV-2) is the causing organism of coronavirus disease 2019 (COVID-19), which has severely affected human life and threatened public health. The pandemic took millions of lives worldwide and caused serious negative effects on human society and the economy. SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) are interesting targets due to their crucial role in viral replication and growth. Since there is only one approved therapy for COVID-19, drug repurposing is a promising approach to finding molecules with potential activity against COVID-19 in a short time and at minimal cost. In this study, virtual screening was performed on the ChEMBL library containing 9923 FDA-approved drugs, using various docking filters with different accuracy. The best drugs with the highest docking scores were further examined for molecular dynamics (MD) studies and MM-GBSA calculations. The results of this study suggest that nadide, cangrelor and denufosol are promising potential candidates against COVID-19. Further in vitro, preclinical and clinical studies of these candidates would help to discover safe and effective anti-COVID-19 drugs.
Keyphrases
- sars cov
- molecular dynamics
- coronavirus disease
- respiratory syndrome coronavirus
- density functional theory
- acute respiratory distress syndrome
- molecular docking
- public health
- molecular dynamics simulations
- extracorporeal membrane oxygenation
- drug induced
- emergency department
- mechanical ventilation
- induced pluripotent stem cells
- intensive care unit
- bone marrow
- drug administration
- climate change
- protein protein