SARS-CoV-2, which causes COVID-19 disease, has proven to be a disastrous pandemic due to its contagious nature. This study has been planned to theoretically explore some antidotes against this virus from natural compounds. A total of 150 compounds from the shogaol class and shogaol derivatives (SDs) have been screened whereas 50 among those, which obeyed Lipinski’s Rule of Five (Ro5), have further been investigated using molecular docking techniques. Furthermore, reference antiviral drug chloroquine (ChQ) and Co-Crystallized inhibitor have also been studied against Mpro of SARS-CoV-2 for comparing the potential of our docked ligands. Surprisingly, 78% of our docked ligands have shown binding energies and inhibition constants lower than ChQ and all ligands showed these values lower than an inhibitor. We further visualized the nature of intermolecular interactions for the best docked six ligands, which have shown higher binding affinities. We have also assessed ADMET properties for three ligands that displayed visually the best intermolecular interactions. Quantum analysis of three selected ligands L4, L5, and L9 has proved their reactivity and kinetic stability. Moreover, molecular dynamic simulations over 60[Formula: see text]ns have been run for free Mpro and its selected three ligand-protein complexes for evaluating conformational stability and residual flexibility of docked complexes. Furthermore, 100[Formula: see text]ns the MD simulations have been performed for two ligand complexes L4, L5 (with negative binding free energy), and inhibitor. Available parameters suggest stable complexes for our ligands and could be active drugs against SARS-CoV-2 in near future.
The world is now facing intolerable damage in all sectors of life because of the deadly COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2. The discovery and development of anti-SARS-CoV-2 drugs have become pragmatic in the time needed to fight against this pandemic. The non-structural protein 3 is essential for the replication of transcriptase complex (RTC) and may be regarded as a possible target against SARS-CoV-2. Here, we have used a comprehensive in silico technique to find potent drug molecules against the NSP3 receptor of SARS-CoV-2. Virtual screening of 150 Isatin derivatives taken from PubChem was performed based on their binding affinity estimated by docking simulations, resulting in the selection of 46 ligands having binding energy greater than −7.1 kcal/mol. Moreover, the molecular interactions of the nine best-docked ligands having a binding energy of ≥ −8.5 kcal/mol were analyzed. The molecular interactions showed that the three ligands (S5, S16, and S42) were stabilized by forming hydrogen bonds and other significant interactions. Molecular dynamic simulations were performed to mimic an in vitro protein-like aqueous environment and to check the stability of the best three ligands and NSP3 complexes in an aqueous environment. The binding energy of the S5, S16, and S42 systems obtained from the molecular mechanics Poisson–Boltzmann surface area also favor the system's stability. The MD and MM/PBSA results explore that S5, S16, and S42 are more stable and can be considered more potent drug candidates against COVID-19 disease.
Supplementary Information
The online version contains supplementary material available at 10.1007/s11696-022-02298-7.
The computational simulations for electronic properties of cadmium (Cd) coordinated L-alanine NDI ligand (H2-l-ala NDI) based complex are the focus of this research. For the first time, the Cd-NDI complex (monomer) has been produced using water as the solvent; this is a new approach to synthesizing the Cd-NDI complex that has not been reported yet. Along with crystallography and Hirsch field analysis, CAM-B3LYP/LANL2DZ and B3LYP/LANL2MB basis sets were used, and in-depth characterisation of the Cd-NDI complex by following DFT and TD-DFT hypothetical simulations. Hyperpolarizabilities, frontier molecular orbitals (FMOs), the density of states (DOS), dipole moment (µ), electron density distribution map (EDDM), transition density matrix (TDM), molecular electrostatic potential (MEP), electron-hole analysis (EHA), and electrical conductivity (σ) have all been studied regarding the Cd-NDI complex. The vibrational frequencies and types of interaction are studied using infrared (IR) and non-covalent interaction (NCI) analysis with iso-surface. In comparison to the Cd-NDI complex with 2.61, 2.42 eV Eg (using CAM-B3LYP/LANL2DZ and B3LYP/LANL2MB basis sets, respectively) and 376 nm λmax, (in case of B3LYP/LANL2MB λmax is higher), H2-l-ala NDI have 3.387 eV Eg and 375 nm λmax, metal-ligand coordination in complex dramatically altered charge transfer properties, such as narrowing band gap (Eg). Based on the electronic properties analysis of Cd-NDI complex, it is predicted that the Cd-NDI complex will have a spectacular (nonlinear optical) NLO response. The Cd-NDI complex is discovered to be advantageous for the creation of future nanoscale devices due to the harmony between the Cd metal and H2-l-ala NDI, in addition to their influences on NLO characteristics.
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