This work aimed at evaluating the inhibitory effect of ten natural bioactive compounds (1-10) as potential inhibitors of SARS-CoV-2-3CL main protease (PDB ID: 6LU7) and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT) by molecular docking analysis. The inhibitory effect of all studied compounds was studied with compared to some proposed antiviral drugs which currently used in COVID-19 treatment such as chloroquine, hydroxychloroquine, azithromycin, remdesivir, baloxvir, lopinavir, and favipiravir. Homology modeling and sequence alignment was computed to evaluate the similarity between the SARS-CoV-2-3CL main protease and other SARS-CoV receptors. ADMET properties of all studied compounds were computed and reported. Also, molecular dynamic (MD) simulation was performed on the compound which has the highest binding affinity inside 6LU7 obtained from molecular docking analysis to study it is stability inside receptor in explicit water solvent. Based on molecular docking analysis, we found that caulerpin has the highest binding affinity inside all studied receptors compared to other bioactive compounds and studied drugs. Our homology modeling and sequence alignment showed that SARS-CoV main protease (PDB ID: 3TNT) shares high similarity with 3CLpro (96.00%). Also, ADMET properties confirmed that caulerpin obeys Lipinski's rule and passes ADMET property, which make it a promising compound to act as a new safe natural drug against SARS-CoV-2-3CL main protease. Finally, MD simulation confirmed that the complex formed between caulerpin and 3CLpro is stable in water explicit and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. Also, binding free energy between caulerpin and 6LU7 confirmed the efficacy of the caulerpin molecule against SARS-CoV-2 main protease. So, this study suggested that caulerpin could be used as a potential candidate in COVID-19 treatment.

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Presently, the SARS-CoV-2 (COVID-19) pandemic has been spreading throughout the world. Some drugs such as lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir have been recommended for COVID-19 treatment by some researchers, but these drugs were not effective enough against this virus. This study based on in silico approaches was aimed to increase the anti-COVID-19 activities of these drugs by using caulerpin and its derivatives as an adjunct drug against SARS-CoV-2 receptor proteins: the SARS-CoV-2 main protease and the SARS-CoV-2 spike protein. Caulerpin exhibited antiviral activities against chikungunya virus and herpes simplex virus type 1. Caulerpin and some of its derivatives showed inhibitory activity against Alzheimer’s disease. The web server ANCHOR revealed higher protein stability for the two receptors with disordered score (< 0.6). Molecular docking analysis showed that the binding energies of most of the caulerpin derivatives were higher than all the suggested drugs for the two receptors. Also, we deduced that inserting NH 2 , halogen, and vinyl groups can increase the binding affinity of caulerpin toward 6VYB and 6LU7, while inserting an alkyl group decreases the binding affinity of caulerpin toward 6VYB and 6LU7. So, we can modify the inhibitory effect of caulerpin against 6VYB and 6LU7 by inserting NH 2 , halogen, and vinyl groups. Based on the protein disordered results, the SARS-CoV-2 main protease and SARS-CoV-2 spike protein domain are highly stable proteins, so it is quite difficult to unstabilize their integrity by using individual drugs. Also, molecular dynamics (MD) simulation indicates that binding of the combination therapy of simeprevir and the candidate studied compounds to the receptors was stable and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. So, this study suggested that caulerpin and its derivatives could be used as a combination therapy along with lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir for disrupting the stability of SARS-CoV2 receptor proteins to increase the antiviral activity of these drugs.

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Chalcogen∙∙∙Chalcogen interactions were investigated within four types of like∙∙∙like and unlike Y=C=Y∙∙∙Y=C=Y complexes (where Y = O, S, and Se). A plethora of quantum mechanical calculations, including molecular electrostatic potential...

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The versatility of the X-T-X3 compounds (where T = C, Si, and Ge, and X = F, Cl, and Br) to participate in tetrel- and halogen-bonding interactions was settled out, at the MP2/aug-cc-pVTZ level of theory, within a series of configurations for (X-T-X3)2 homodimers. The electrostatic potential computations ensured the remarkable ability of the investigated X-T-X3 monomers to participate in σ-hole halogen and tetrel interactions. The energetic findings significantly unveil the favorability of the tetrel···tetrel directional configuration with considerable negative binding energies over tetrel···halogen, type III halogen···halogen, and type II halogen···halogen analogs. Quantum theory of atoms in molecules and noncovalent interaction analyses were accomplished to disclose the nature of the tetrel- and halogen-bonding interactions within designed configurations, giving good correlations between the total electron densities and binding energies. Further insight into the binding energy physical meanings was invoked through using symmetry-adapted perturbation theory-based energy decomposition analysis, featuring the dispersion term as the most prominent force beyond the examined interactions. The theoretical results were supported by versatile crystal structures which were characterized by the same type of interactions. Presumably, the obtained findings would be considered as a solid underpinning for future supramolecular chemistry, materials science, and crystal engineering studies, as well as a fundamental linchpin for a better understanding of the biological activities of chemicals.