Development of SARS-CoV-2 Inhibitors Using Molecular Docking Study with Different Coronavirus Spike Protein and ACE2

Abstract

The novel coronavirus SARS-CoV-2 is an acute respiratory tract infection that emerged in Wuhan city, China. The spike protein of coronaviruses is the main driving force for host cell recognition and is responsible for binding to the ACE2 receptor on the host cell and mediates the fusion of host and viral membranes. Recognizing compounds that could form a complex with the spike protein (S-protein) potently could inhibit SARS-CoV-2 infections. The software was used to survey 300 plant natural compounds or derivatives for their binding ability with the SARS-CoV-2 S-protein. The docking score for ligands towards each protein was calculated to estimate the binding free energy. Four compounds showed a strong ability to bind with the S-protein (neohesperidin, quercetin 3-O-rutinoside-7-O-glucoside, 14-ketostypodiol diacetate, and hydroxypropyl methylcellulose) and used to predict its docking model and binding regions. The highest predicted ligand/protein affinity was with quercetin 3-O-rutinoside-7-O-glucoside followed by neohesperidin. The four compounds were also tested against other related coronavirus and showed their binding ability to S-protein of the bat, SARS, and MERS coronavirus strains, indicating that they could bind and block the spike activities and subsequently prevent them infection of different coronaviruses. Molecular docking also showed the probability of the four ligands binding to the host cell receptor ACE2. The interaction residues and the binding energy for the complexes were identified. The strong binding ability of the four compounds to the S-protein and the ACE2 protein indicates that they might be used to develop therapeutics specific against SARS-CoV-2 and close related human coronaviruses.

Monoclonal antibodies: a remedial approach to prevent SARS-CoV-2 infection

“…Combination of these findings led them to design a chimeric antibody by conjugating CDRH3 of regdanivimab on sotrovimab skeleton that could combat against escape mutants (Das et al 2021). Similar docking studies performed by analysing docking energies of natural compounds with S-protein of virus and ACE2 receptor of host cell indicate quercetin 3-O-rutinoside-7-O-glucoside and neohesperidin having strong ligand-protein affinity (Shamkh and Pratiwi 2021). Based on cryoelectron microscopy structural data of RBD and S-protein as well as the screening of memory B-cells using PBMC (Peripheral Blood Mononuclear Cells) collected from both SARS-CoV-2 and SARS-CoV infected individuals, few human monoclonal antibodies were identified which can be designated as possible treatment options for severe SARS-CoV-2 infection (Table 1) (Pinto et al 2020).…”

Molecular modeling study of micro and nanocurcumin with in vitro and in vivo antibacterial validation

“…2D/3D representations of structures of the selected compound were converted to Simplified Molecular-Input Line-Entry System (SMILES) notations and submitted to the swissADME online server http://www.swissadme.ch/ for calculation and knowledge about structure features. The swissADME was used to identify physicochemical characteristics as well as predict absorption, distribution, metabolism, and excretion (ADME) parameters, the drug-like nature, physicochemical properties of the compounds 28 . Now, the two chemicals (curcumin and ciprofloxacin) are ready to dock with the four most vital and positively identified bacterial quorum-sensing proteins obtained from the protein data bank (PDB) https://www.rcsb.org under accession numbers 6itC, 4l5J, 6yiZ, and 4g4K for the isolates B. subtilis, E. coli, P. aeruginosa , and S. aureus, respectively, all water molecules and ligands were removed, while hydrogen atoms were added to the target proteins.…”

Antibacterial and In silico evaluation of Micro and Nanocurcumin, Assessment of Wound Healing Potentiality

“…Physicochemical characteristics of selected compound structures were converted to simpli ed molecular-input line-entry system (smiles) notations and submitted to the swissADME online server for calculation and knowledge about structure features. The swissADME was used to identify physicochemical characteristics as well as predict absorption, distribution, metabolism, and excretion (ADME) parameters, also, drug-like nature, pharmacokinetic properties, and medicinal chemistry of the compounds [20]. The two chemicals are ready to dock with the target bacterial proteins obtained from the protein data bank (https://www.rcsb.org) under accession numbers 6itc, 4l5j, 6yiz, and 4g4k for the isolates B. subtilis, E. coli, p. aeruginosa, and S. aureus respectively, Pre-docking, all water molecules and ligands were removed while hydrogen atoms were added to the target proteins.…”

“…This technique was used to estimate the binding modes and a nities of each chemical by docking the structures of the four proteins of accession numbers 6itc, 4l5j, 6yiz and 4g4k. The docking program operates in such a way that it can obtain the docking parameter in MOE software and SAMSON 2020 software, a visual representation of the docked poses of high-scoring compounds was often necessary because many of the ligands were docked in a variety of different directions [20].…”