Synthesis, in silico study (DFT, ADMET) and crystal structure of novel sulfamoyloxy-oxazolidinones: Interaction with SARS-CoV-2.

A new series of sulfamoyloxyoxazolidinone (SOO) derivatives have been synthesized and characterized by single-crystal X-ray diffraction, NMR, IR, MS and EA. Chemical reactivity and geometrical characteristics of the target compounds were investigated using DFT method. The possible binding mode between SOO and Main protease (Mpro) of SARS-CoV-2 and their reactivity were studied using molecular docking simulation. Single crystal X-ray diffraction showed that SOO crystallizes in a monoclinic system with P 2 1 space group. The binding energy of the SARS-CoV-2/Mpro-SOO complex and the calculated inhibition constant using docking simulation showed that the active SOO molecule has the ability to inhibit SARS-CoV2. We studied the prediction of absorption, distribution, properties of metabolism, excretion and toxicity (ADMET) of the synthesized molecules.

In-silico modelling of fullerene and fullerene adsorbed by nO2 molecules (n(O2)@Cm with n = 1, 2, 4 and m = 48 and 60) as potential SARS-CoV-2 inhibitors

COVID-19 pandemic started more than a year ago and has infected more than 115 million of people from ~210 countries and >2.5 million of deaths worldwide being reported without any commercial and effective treatment or vaccine being yet released. However, recent studies on nanomaterials such as fullerenes, carbon nanotubes and graphene showed that they possess anti-inflammatory, antiviral, anti-oxidant and anti-HIV properties. Herein, the interactions which established between the fullerenes Cm (m = 48, 60, 70, 80, 84 and 86) and the spike protein (SP) of SARS-CoV-2 and the human ACE2 receptor have been investigated based on the density functional theory (DFT) method with the CAM-B3LYP functional and the 6-31G* basis. The results of this study show that C48 exhibited as potential inhibitor of SARS-CoV-2. Because of the presence of heteroatoms on the surface of fullerenes which systematically reduce energy gaps, which in turn increase their reactivities. The oxygen adsorbed by fullerenes increases the number of non-covalent contacts and involves a large number of hydrogen bonds, while decreasing the binding energies. Thus, the hACE2-SP-4O2@C60 complex is strongly recommended for inhibiting SARS-CoV-2 in the final phase of contamination.Graphic abstractStabilizing interactions between fullerenes and the spike protein of SARS-CoV-2.

Crystal structure, Hirshfeld surface and reactivity of novel ligand-LAT1 derived from dehydroacetic acid: intermolecular interactions with SARS-Cov-2/main protease

The crystals of new ligand, namely (3E)-6-methyl-3-{1-[(pyridin-3-ylmethyl) amino] ethylene}-2H-pyran-2, 4(3H)-dione) (LAT1), were synthesized using the evaporation solution technique. Single-crystal X-ray diffraction and physico-chemical characterization (ATR, proton and carbon-13 NMR and UV-Visible) of LAT1 were reported. In addition, Hirshfeld surface analysis (HSA) of the solid compound, structure optimization, Mulliken and NBO charges, global indices of reactivity, local reactivity descriptors and molecular electrostatic potential (MEP) of the ligand were investigated theoretically. XRD analysis showed that LAT1 crystallizes in the triclinic space group P-1 and the structure was stabilized through hydrogen bonds. HAS revealed that H…H (46.5%) and O…H (25.7%) contacts are in control of crystal stacking. The energy gap (4.679 eV) and reactivity descriptors indicate the stability of LAT1. The Mulliken and NBO charges showed that the protons have a positive charge and the heteroatoms exhibit negative charges. The Fukui function and MEP study revealed that the heteroatoms are the most reactive sites for an electophilic attack on the ligand. Molecular docking simulation shows that the significant binding affinity of LAT1 with SARS-CoV-2/Mpro is due to the formation of high number of hydrogen bonds.

Crystal structure, chemical reactivity, kinetic and thermodynamic studies of new ligand derived from 4-hydroxycoumarin: Interaction with SARS-CoV-2.

Currently, Covid-19 pandemic infects staggering number of people around the globe and causes a high rate of mortality. In order to fight this disease, a new coumarin derivative ligand (4-[(pyridin-3-ylmethyl) amino]-2H-chromen-2-one) (LTA) has been synthesized and characterized by single-crystal X-ray diffraction, NMR, ATR, UV-Visible and cyclic voltammetry. Chemical reactivity, kinetic and thermodynamic studies were investigated using DFT method. The possible binding mode between LTA and Main protease (Mpro) of SARS-CoV-2 and their reactivity were studied using molecular docking simulation. Single crystal X-ray diffraction showed that LTA crystallizes in a monoclinic system with P2 1  space group. The reactivity descriptors such as nucleophilic index confirm that LTA is more nucleophile, inducing complexation with binding species like biomolecules. The kinetic and thermodynamic parameters showed that the mechanism of crystal formation is moderately exothermic. The binding energy of the SARS-CoV-2/Mpro-LTA complex and the calculated inhibition constant using docking simulation showed that the active LTA molecule has the ability to inhibit SARS-CoV-2.