Dataset Information

Insilico drug repurposing using FDA approved drugs against Membrane protein of SARS-CoV-2.

ABSTRACT: The novel coronavirus (SARS-CoV-2) outbreak has started taking away the millions of lives worldwide. Identification of known and approved drugs against novel coronavirus disease (COVID-19) seems to be an urgent need for the repurposing of the existing drugs. So, here we examined a safe strategy of using approved drugs of SuperDRUG2 database against modeled membrane protein (M-protein) of SARS-CoV-2 which is essential for virus assembly by using molecular docking-based virtual screening. A total of 3639 drugs from SuperDRUG2 database and additionally 14 potential drugs reported against COVID-19 proteins were selected. Molecular docking analyses revealed that nine drugs can bind the active site of M-protein with desirable molecular interactions. We therefore applied molecular dynamics simulations and binding free energy calculation using MM-PBSA to analyze the stability of the compounds. The complexes of M-protein with the selected drugs were simulated for 50 ns and ranked according to their binding free energies. The binding mode of the drugs with M-protein was analyzed and it was observed that Colchicine, Remdesivir, Bafilomycin A1 from COVID-19 suggested drugs and Temozolomide from SuperDRUG2 database displayed desirable molecular interactions and higher binding affinity towards M-protein. Interestingly, Colchicine was found as the top most binder among tested drugs against M-protein. We therefore additionally identified four Colchicine derivatives which can bind efficiently with M-protein and have better pharmacokinetic properties. We recommend that these drugs can be tested further through in vitro studies against SARS-CoV-2 M-protein.

SUBMITTER: Peele KA

PROVIDER: S-EPMC7934671 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The RNA-dependent RNA polymerase (RdRp) and 3C-like protease (3CLpro) from SARS-CoV-2 play crucial roles in the viral life cycle and are considered the most promising targets for drug discovery against SARS-CoV-2. In this study, FDA-approved drugs were screened to identify the probable anti-RdRp and 3CLpro inhibitors by molecular docking approach. The number of ligands selected from the PubChem database of NCBI for screening was 1760. Ligands were energy minimized using Open Babel. The RdRp and 3CLpro protein sequences were retrieved from the NCBI database. For Homology Modeling predictions, we used the Swiss model server. Their structure was then energetically minimized using SPDB viewer software and visualized in the CHIMERA UCSF software. Molecular dockings were performed using AutoDock Vina, and candidate drugs were selected based on binding affinity (∆G). Hydrogen bonding and hydrophobic interactions between ligands and proteins were visualized using Ligplot and the Discovery Studio Visualizer v3.0 software. Our results showed 58 drugs against RdRp, which had binding energy of - 8.5 or less, and 69 drugs to inhibit the 3CLpro enzyme with a binding energy of - 8.1 or less. Six drugs based on binding energy and number of hydrogen bonds were chosen for the next step of molecular dynamics (MD) simulations to investigate drug-protein interactions (including Nilotinib, Imatinib and dihydroergotamine for 3clpro and Lapatinib, Dexasone and Relategravir for RdRp). Except for Lapatinib, other drugs-complexes were stable during MD simulation. Raltegravir, an anti-HIV drug, was observed to be the best compound against RdRp based on docking binding energy (-9.5 kcal/mole) and MD results. According to the MD results and binding energy, dihydroergotamine is a suitable candidate for 3clpro inhibition (-9.6 kcal/mol). These drugs were classified into several categories, including antiviral, antibacterial, anti-inflammatory, anti-allergic, cardiovascular, anticoagulant, BPH and impotence, antipsychotic, antimigraine, anticancer, and so on. The common prescription-indications for some of these medication categories appeared somewhat in line with manifestations of COVID-19. We hope that they can be beneficial for patients with certain specific symptoms of SARS-CoV-2 infection, but they can also probably inhibit viral enzymes. We recommend further experimental evaluations in vitro and in vivo on these FDA-approved drugs to assess their potential antiviral effect on SARS-CoV-2.

Dataset Information

Insilico drug repurposing using FDA approved drugs against Membrane protein of SARS-CoV-2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure