Discovery of potential SARS-CoV 3CL protease inhibitors from approved antiviral drugs using: virtual screening, molecular docking, pharmacophore mapping evaluation and dynamics simulation

Abstract

The spread of corona-virus disease 2019 (COVID-19) has been faster than any other corona-viruses that have succeeded in crossing the animal-human barrier. This disease, caused by the severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2/2019-nCoV) posing a serious threat to global public health and local economies. There are three responsible for this disease; SARS-CoV-2, SARS-CoV and MERS-CoV. Whereas our goal is to test the affinity for a new class of compounds obtained from a hybridization of Chloroquine, Amodiaquine and Mefloquine with three targets SARS-CoV-2, SARS-CoV and MERS-CoV, in order to find new compounds as new inhibitors against Covid-19. In this work, we first used: the molecular docking/dynamics methods and ADME properties to study interaction and affinity between eight new compounds against three targets involved in the Covid-19. The results of the docking simulations and dynamics revealed that inhibitor of the malaria (Ligand 87) has an affinity to interact with SARS-CoV-2, SARS-CoV and MERS-CoV targets and they can be good inhibitors for treatment of Covid-19. Moreover, they give best affinity compared to the Remdesivir and Chloroquine and other clinical tests. The Pharmacokinetics was justified by means of lipophilicity and high coefficient of skin permeability. The in silico evaluation of ADME and drug-likeness revealed that L87 has higher absorption in the intestines with good bioavailability. However, an additional in vitro and/or in vivo experimental study should make it possible to verify the theoretical results obtained in silico. Communicated by Ramaswamy H. Sarma

In vitro and in silico studies of prenylated phenylpropanoids of green propolis and their derivatives against cariogenic bacteria

“…The molecular docking studies were carried out to identify the binding interactions of the most active compounds 2 and 8 within the binding site residue of the targets by using MOE software [46], and the docking protocol steps were followed and detailed in our previous research [47,48] The re-dock of all native ligands to their targets was conducted using "Dock Option" implemented in the MOE software [46] to validate the used method. The RSMD values of the obtained complexes (Targets-Crystallized ligands) were less than 2.50 Å [49], meaning that the docking method is accurate and successful.…”

Evaluation of the Antiparasitic and Antifungal Activities of Synthetic Piperlongumine‐Type Cinnamide Derivatives: Booster Effect by Halogen Substituents

“…The docking procedure has been described earlier. [44][45][46] The PDB file -1SA0 was downloaded from the Protein Data Bank for the three dimensional structure of tubulin. First, the 3D Structures of test compounds, 1 a-d, 3 a-c, and 4 a-c were built with MOE software, and we minimized them by using the MMFF94x force-field with reaction-field electrostatics (Din = 1, Dout = 80) using a flat bottom tether (10.0 kcal/ mol, 0.25 Å), which was applied to all atoms.…”

“…The software source was The Chemical Computing Group Inc., Montreal, QC, Canada. The docking procedure has been described earlier [44–46] . The PDB file – 1SA0 was downloaded from the Protein Data Bank for the three dimensional structure of tubulin.…”

Inhibition of the RNA Polymerase of Tick-Borne Encephalitis Virus: A Molecular Docking and Simulation Study

“…In many earlier studies it has been observed that the highest dock score achieved by molecular docking does not imply that the molecule is a potent lead; until molecular dynamics simulations are required to validate this conclusion [46]. To determine the stability of the proteins and ligandprotein complexes, molecular dynamics simulations were used [47].…”