“…6 , the apo-protein displayed a SASA value of 148.6577 nm 2 while M pro -Rutin and M pro -Isorhamnetin-3-O-rutinoside complexes exhibit 151.7073 nm 2 and 148.9542 nm 2 respectively. Rutin complex exhibits a slightly higher SASA value than other two complex systems, which recommends that Rutin induces protein expansion and thus increases the solvent surface accessible on the protein [ 53 , 54 ] . Fig.…”
COVID-19 as per early April 2021, has globally exceeded 129 million cases and is the cause of about 2.8 million deaths. Since the illness is known to have a wide array of symptoms, in addition to its ability to spread rapidly through contact and the complexity involved in developing drugs, there is an immediate need to look into alternative treatment regimes. This study was intended to identify potential antiviral compounds from
Moringa oleifera
against the selected target main protease (M
pro
), which is vital for the survival of the virus.
In silico
molecular docking and dynamics was performed to determine a potential inhibitor against M
pro
. Phytochemicals of
Moringa olifera
reported in literature were retrieved from public databases and employed for molecular docking studies against M
pro
. PyRx software was used to perform docking analysis. Visualization of amino acid interactions between the ligand and target was performed using Maestro and Discovery studio visualizer to analyze the type of interactions. Compounds displaying high binding affinities were subjected for analysis of pharmacokinetic studies, later molecular dynamics (MD) and MM-PBSA studies was conducted over selected compounds using GROMACS. Rutin and Isorhamnetin-3-O-rutinoside, both flavonoids thoroughly studied for their medicinal properties showcased strong interactions and the highest binding affinity of −8.9 kcal/mol with the M
pro
. The binding energy calculated employing MM-PBSA for Rutin and Isorhamnetin-3-O-rutinoside were −86.832 kJ/mol and −72.984 kJ/mol, respectively. The overall studies revealed that Rutin and Isorhamnetin-3-O-rutinoside are portenial in inhibiting the SARS-CoV-2 M
pro
and can be validated through
in-vitro
and
in-vivo
studies.
“…6 , the apo-protein displayed a SASA value of 148.6577 nm 2 while M pro -Rutin and M pro -Isorhamnetin-3-O-rutinoside complexes exhibit 151.7073 nm 2 and 148.9542 nm 2 respectively. Rutin complex exhibits a slightly higher SASA value than other two complex systems, which recommends that Rutin induces protein expansion and thus increases the solvent surface accessible on the protein [ 53 , 54 ] . Fig.…”
COVID-19 as per early April 2021, has globally exceeded 129 million cases and is the cause of about 2.8 million deaths. Since the illness is known to have a wide array of symptoms, in addition to its ability to spread rapidly through contact and the complexity involved in developing drugs, there is an immediate need to look into alternative treatment regimes. This study was intended to identify potential antiviral compounds from
Moringa oleifera
against the selected target main protease (M
pro
), which is vital for the survival of the virus.
In silico
molecular docking and dynamics was performed to determine a potential inhibitor against M
pro
. Phytochemicals of
Moringa olifera
reported in literature were retrieved from public databases and employed for molecular docking studies against M
pro
. PyRx software was used to perform docking analysis. Visualization of amino acid interactions between the ligand and target was performed using Maestro and Discovery studio visualizer to analyze the type of interactions. Compounds displaying high binding affinities were subjected for analysis of pharmacokinetic studies, later molecular dynamics (MD) and MM-PBSA studies was conducted over selected compounds using GROMACS. Rutin and Isorhamnetin-3-O-rutinoside, both flavonoids thoroughly studied for their medicinal properties showcased strong interactions and the highest binding affinity of −8.9 kcal/mol with the M
pro
. The binding energy calculated employing MM-PBSA for Rutin and Isorhamnetin-3-O-rutinoside were −86.832 kJ/mol and −72.984 kJ/mol, respectively. The overall studies revealed that Rutin and Isorhamnetin-3-O-rutinoside are portenial in inhibiting the SARS-CoV-2 M
pro
and can be validated through
in-vitro
and
in-vivo
studies.
“…The radius of gyration was investigated as a function of the protein structure's compression and the protein's changes over the simulation time [ 38 ].…”
Section: Methods and Computational Detailsmentioning
The main protease of SARS-CoV-2 is a critical target for the design and development of antiviral drugs. 2.5 M compounds were used in this study to train an LSTM generative network via transfer learning in order to identify the four best candidates capable of inhibiting the main proteases in SARS-CoV-2. The network was fine-tuned over ten generations, with each generation resulting in higher binding affinity scores. The binding affinities and interactions between the selected candidates and the SARS-CoV-2 main protease are predicted using a molecular docking simulation using AutoDock Vina. The compounds selected have a strong interaction with the key MET 165 and Cys145 residues. Molecular dynamics (MD) simulations were run for 150ns to validate the docking results on the top four ligands. Additionally, root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), and hydrogen bond analysis strongly support these findings. Furthermore, the MM-PBSA free energy calculations revealed that these chemical molecules have stable and favorable energies, resulting in a strong binding with Mpro's binding site. This study's extensive computational and statistical analyses indicate that the selected candidates may be used as potential inhibitors against the SARS-CoV-2 in-silico environment. However, additional in-vitro, in-vivo, and clinical trials are required to demonstrate their true efficacy.
“…[1]. The Rg measures the strength of the macromolecular system, through the root mean square of the distance between the axis of rotation and the center of mass obtained in the MD simulation, the parameter shows the changes over time in the protein structure, evaluating the compaction and system stability [61,76]. The calculated surface area is the canonical SASA surface area and includes the total hydrophobic, hydrophilic and solvent-accessible surface area of the protein molecule, the extent to which amino acids interact with the solvent, and the protein core is proportional to the area surface exposed to solvent.…”
Section: The Radius Of Gyration and Solvent-accessible Surface Areamentioning
confidence: 99%
“…To automatically perform all the steps necessary to estimate the free binding energy of the complex, we used the MM/PBGBSA scripts (MM: Molecular Mechanics; PB: Poisson-Boltzmann; GB: Generalized Born; SA: Surface Area) [29,61,66] included in GROMACS [1]. However, it is generally expected that no signi cant conformational changes will occur after connection, so snapshots of all three species can be taken from a single trajectory.…”
Molecular modeling techniques are used to describe the process of interaction between nanotubes and the main structures of the Covid-19 virus: the envelope protein, the main protease, and the Spike glycoprotein. Molecular docking studies show that the ligands have interaction characteristics capable of adsorbing the structures. Molecular dynamics simulations provide information on the mean squared deviation of atomic positions between 0.5 and 3.0 Å. The Gibbs free energy model and solvent accessible surface area approaches are used. Through the results obtained through molecular dynamics simulations, it is noted that the zigzag nanotube prefers to interact with E-pro, M-pro, and S-gly, respectively. Molecular couplings and free energy showed that the S-gly active site residues strongly interact with zigzag, chiral, and armchair nanotubes, in this order. The interactions demonstrated in this manuscript may predict some promising candidates for virus antagonists, which may be confirmed through experimental approaches.
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