Therapeutic strategies for Covid-19 based on molecular docking and dynamic studies to the ACE-2 receptors, Furin, and viral spike proteins

Abstract

SARS-CoV-2 is a pandemic virus that caused infections and deaths in many world countries, including the Middle East. The virus-infected human cells by binding via ACE-2 receptor through the Spike protein of the virus with Furin's help causing cell membrane fusion leading to Covid-19-cell entry. No registered drugs or vaccines are triggering this pandemic viral disease yet. Our present work is based on molecular docking and dynamics simulation that performed to spike protein-ACE-2 interface complex, ACE-2 receptor, Spike protein (RBD), and Furin as targets for new small molecules. These drugs target new potential therapies to show their probabilities toward the active sites of mentioned proteins, strongly causing inhibition and/or potential therapy for covid-19. All target proteins were estimated against new target compounds under clinical trials and repurposing drugs currently present. Possibilities of those molecules and potential therapeutics acting on a certain target were predicted. MD simulations over 200 ns with molecular mechanics-generalized Born surface area (MMGBSA) binding energy calculations were performed. The structural and energetic analyses demonstrated the stability of the ligands-M Pros complex. Our present work will introduce new visions of some biologically active molecules for further studies in-vitro and in-vivo for Covid-19, repurposing of these molecules should be taking place under clinical works and offering different strategies for drugs repurposing against Covid-19 diseases. Communicated by Ramaswamy H. Sarma.

Evaluation of the anti-proliferative activity of 2-oxo-pyridine and 1′H-spiro-pyridine derivatives as a new class of EGFRWtand VEGFR-2 inhibitors with apoptotic inducers

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A new exploration toward adamantane derivatives as potential anti‐MDR agents: Design, synthesis, antimicrobial, and radiosterilization activity as potential topoisomerase IV and DNA gyrase inhibitors

“…Molecular docking studies for the most active adamantane derivatives and positive control (CIP and NV) were evaluated inside the active site of DNA gyrase (PDB: 4URO) and topoisomerase IV (PDB: 4EMV) using Molecular operating Environmental (MOE; Rizk et al, 2021). First, the structure of the synthesized adamantane and positive controls were built using chembiodraw 2014 and then exported to MOE, where the hydrogen bond was added, and the structure exposed to energy was minimized using MMFF94x forcefield as described previously (Ezzat et al, 2022; Ibrahim et al, 2022; Khattab et al, 2022). The active site of DNA gyrase (PDB: 4URO) was generated according to the previously reported method (Alotaibi & Amer, 2020; Fayed et al, 2022), where the trigonal matcher placement method was used to generate the optimized 3D structure of ligand inside the active site of pocket.…”

Development and radiosterilization of new hydrazono‐quinoline hybrids as DNA gyrase and topoisomerase IV inhibitors: Antimicrobial and hemolytic activities against uropathogenic isolates with molecular docking study

“…Molecular docking study for the most active hydrazono‐quinoline and positive control (ciprofloxacin and levofloxacin) were evaluated inside the active site of DNA gyrase (PDB: 4URO) and topoisomerase IV (PDB: 4EMV) using Molecular operating Environmental (MOE) (Eldeeb et al, 2022; El‐Kalyoubi, et al, 2022; Ragab, Ammar et al, 2022; Saadon et al, 2022). Firstly, the structure of the synthesized quinoline and positive controls were built using chembiodraw 2014 and then exported to MOE (Hassan et al, 2022; Rizk et al, 2021, Rizk et al, 2020), where the hydrogen bond added, and the structure exposed to energy minimized using MMFF94x forcefield as described previously (Ezzat et al, 2022; Ibrahim et al, 2022; Khattab et al, 2022). The active site of DNA gyrase (PDB: 4URO) was generated according to the previously reported method (Alotaibi & Amer, 2020), where the Trigonal matcher placement method was used to generate the optimized 3D structure of ligand inside the active site of pocket.…”