Developing a safe and effective antiviral treatment takes a decade, however, when it comes to the coronavirus disease (COVID-19), time is a sensitive matter to slow the spread of the pandemic. Screening approved antiviral drugs against COVID-19 would speed the process of finding therapeutic treatment. The current study examines commercially approved drugs to repurpose them against COVID-19 virus main protease using structure-based in-silico screening. The main protease of the coronavirus is essential in the viral replication and is involved in polyprotein cleavage and immune regulation, making it an effective target when developing the treatment. A Number of approved antiviral drugs were tested against COVID-19 virus using molecular docking analysis by calculating the free natural affinity of the binding ligand to the active site pocket and the catalytic residues without forcing the docking of the ligand to active site. COVID-19 virus protease solved structure (PDB ID: 6LU7) is targeted by repurposed drugs. The molecular docking analysis results have shown that the binding of Remdesivir and Mycophenolic acid acyl glucuronide with the protein drug target has optimal binding features supporting that Remdesivir and Mycophenolic acid acyl glucuronide can be used as potential anti-viral treatment against COVID-19 disease.

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Since December 2019, a pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in China and has rapidly spread around the world. The virus has caused a global outbreak of viral pneumonia, which has been known as coronavirus disease . This study aims to examine known direct acting antivirals (DAA) against SARS-CoV-2 papin like protease. A number of known antiviral drugs were tested as potential SARS-CoV-2 virus inhibitors using the molecular docking analysis to examine the free natural affinity of the binding ligand to catalytic residues and substrate binding pockets without forcing the docking of ligand to active site. SARS-CoV-2 papin like protease solved structure (PDB ID: 6W9C) is targeted by direct acting antiviral drugs. The geometry of all inhibitors was optimized using Avogadro software. Molecular Docking was performed using AutoDock Vina software. Protein-Ligand Interaction Profiler (PLIP) web server was used to analyze the interactions formed between drugs and SARS-CoV-2 PLpro. Mycophenolic acid and 4′-Tosyl Mycophenolic Acid-d3 was tested against SARS-CoV-2 papin like protease mutant C111S (PDB ID: 6WRH). Mycophenolic acid showed mild efficacy against the mutant strain. The molecular docking analysis results indicated that Mycophenolic acid and 4′-Tosyl Mycophenolic Acid-d3 has good binding affinities to the protein drug target and showed the highest probabilities to bind to catalytic residues of target protein (30% and International Journal of Intelligent Computing and Information Sciences https://ijicis.journals.ekb.eg/ 150 A. Nassar et al. 50%) respectively, suggesting their potential use for COVID-19 treatment. Molecular dynamic simulation was used to confirm the stability of the complexes formed.

COVID-19 outbreak associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) raised health concerns across the globe and has been considered highly transmissible between people. In attempts for finding therapeutic treatment for the new disease, this work has focused on examining the polymerase inhibitors against the SARS-CoV-2 nsp12 and co-factors nsp8 and nsp7. Several polymerase inhibitors were examined against PDB ID: 6M71 using computational analysis evaluating the ligand’s binding affinity to replicating groove to the active site. The findings of this analysis showed Cytarabine of -5.65 Kcal/mol with the highest binding probability (70%) to replicating groove of 6M71. The complex stability was then examined over 19 ns molecular dynamics simulation suggesting that Cytarabine might be possible potent inhibitor for the SARS-CoV-2 RNA Dependent RNA Polymerase.

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