Molecular electron density theory has been performed with the B3LYP/6-31(d,p) method to study the [3+2] cycloaddition processes between azidobenzene and propionaldehyde, the reactivity indices, activation and reaction energies are computed. The reaction and activation energies indicate that this [3+2] cycloaddition reaction is regiospecific, in good agreement with the experimental results. ELF examination revealed that the mechanism of these cycloaddition reactions takes place in two steps. In addition, a docking approach was performed on the products investigated, and the interaction with the protein protease COVID-19 (PDB ID: 6LU7), the results confirm that the presence of triazole and isoxazole rings increases the affinity of these products.

In this work, ribonucleoside products have been prepared by employing stannic tetrachloride (SnCl4) and natural phosphate as catalysts. The obtained result suggests that this catalyst facilitates the reactions of ribonucleoside-like products in a stereo-controlled manner, exhibiting β-selectivity when reacting with trimethylsilyl uracil, the ribonucleosides derivatives were obtained in suitable yields. In addition, we have performed the molecular docking analysis, demonstrated that the synthesized compounds have potential for antiviral activity against the omicron variant of coronavirus, and the D3, D4, E and F products have a higher binding energy than the molnupiravir drug, indicating that these products may be a probable drugs for the omicron variant.

The inhibiting effect of chloroquine compounds (ChCs) on the SARS-CoV-2 virus represents a highly debated form of study owing to the emerging proposals of mechanistic implications for exploring the mode of action of ChCs on the virus. Keeping in view the emerging significance of chloroquine derivatives, the present study was performed to screen one hundred and ninety known chloroquine derivatives for their interaction with several SARS-CoV-2 target proteins by molecular docking and molecular dynamics simulations to obtain an in-depth understanding of the potential hits of these compounds against SARS-CoV-2. A total of 190 molecules from the chloroquine family were screened for the identification of potential new inhibitors of the three therapeutic target proteins of SARS-CoV-2, namely Mpro (master protease), PLpro (papain-like protease) and SGp-RBD (spike glycoprotein receptor binding domain). The ChCs bound to SARS-COV-2 Mpro, PLpro, and SGp-RBD were generated by molecular docking and molecular dynamics simulations. Herein, a comparative analysis of chloroquine family products and a well-known drug against SARS-CoV-2, called Remdesivir, has also been presented. This investigation is intended to study the mechanism of interaction between ChCs and the SARS-CoV-2 virus and explore the unprecedented areas associated with the inhibitory activity of ChCs against this virus.

Application of the Molecular Electron Density Theory (MEDT) for the exploration of the [3+2] cycloaddition processes between methyl propynoate 1 and difluoromethyldiazomethane T-1, have been implemented using the DFT/B3LYP/6-311(d,p) level of theory. According to an examination of conceptual DFT indices, difluoromethyldiazomethane (T-1) participates in this reaction as a nucleophile, while methyl propynoate (1) should be considered as an electrophile. This cyclization is regiospecific, as evidenced by the activation and reaction energies, this agrees with the experiment's findings. It was discovered throughout ELF analysis that analyzed [3+2] cycloaddition is realised by a two-step mechanism. In addition, study of interactions of the products studied in this paper with the protein protease Covid-19 (PDB ID: 7R98) were carried out, by means of molecular docking study). The results indicate that the occurrence of the transfer of the proton to the nitrogen atom, increases the affinity of these products to the protein (CA32-F1 and CA32-F2).