Search

A second‐generation HIV protease enzyme inhibitor, darunavir is used in combination therapy for patients with history of prior antiretroviral treatments. It inhibits the cleavage of HIV encoded gag‐pol polyprotein in cells contaminated by a virus and thereby hinders the development of mature and infectious new virions. In this paper, optimization of molecular geometry of darunavir has been obtained by Density Functional Theory based B3LYP and ωB97XD methods with 6–311+G(d,p) basis set. The electro‐optical, global reactivity descriptors, and UV–visible spectrum of the drug have been examined using both the functionals. Further, binding affinity of darunavir at different sites of protein receptor (PDB ID: 5b18) has been analyzed using molecular docking technique. Results have been used to discuss electro‐optical and electronic properties of the drug along with its binding affinities with protein receptors. [ABSTRACT FROM AUTHOR]

Corticosteroids are a form of medication that helps to reduce inflammation in the body. They also suppress the body immune system and are prescribed as medicines to treat diseases such as asthma, arthritis, lupus, and allergies because they reduce swelling, itching, redness, and allergic reactions. Further, corticosteroids have been recommended for use in different formulations and doses with varying durations in patients suffering with Covid-19 infection. In view of these facts, most commonly used corticosteroids namely, dexamethasone, prednisolone and hydrocortisone have been chosen in this study. Molecular geometries of these steroids have been optimized using density functional theory technique at B3LYP/6-31 + G(d,p) level. Further, optimized structures have been used for molecular docking that has been performed on SwissDock web server. The binding energies between corticosteroids and residues of the glucocorticoid receptor (1M2Z) represent that there exist several binding sites between drug molecules and residues of the target protein. Therefore, most preferred binding sites are taken for the molecular dynamics simulation which elucidates the stability of drug-protein complexes. Results have been used to discuss the binding affinities of dexamethasone, prednisolone and hydrocortisone with protein receptor along with various electronic properties of the corticosteroid drugs. [ABSTRACT FROM AUTHOR]

The compound (2H-3, 1-benzoxazin-2-one,6-chloro-4-(cyclopropylethynyl)-1,4- dihydro-4-(trifluoromethyl)-,(4S)), commonly known as efavirenz, is an anti-HIV drug. It is used in combination with antiretroviral agents for the treatment of HIV-1 infection. In this work, the geometry of efavirenz has been optimized by density functional method at B3LYP level. Also, the electronic structure and molecular properties of efavirenz have been investigated. Further, the optimized structure is used for molecular docking study that has been carried out by SwissDock web server in order to check the binding affinity of efavirenz with 3EO9 receptor. The binding energies between efavirenz and the residues of the 3EO9 receptor demonstrate that there exist various attractive binding sites between efavirenz and residue positions of the target protein. The best binding site is further taken for the molecular dynamics simulation which also validates the result of molecular docking. Results have been discussed in order to elucidate the binding mechanism of efavirenz with protein receptor along with various physico-chemical properties of the drug molecule. [ABSTRACT FROM AUTHOR]

Nevirapine is used in the treatment of Human Immunodeficiency Virus Type 1 (HIV-1) infection. The structure of nevirapine belongs to the dipyridodiazepinone class of chemical. In the present work, molecular geometries of nevirapine drug, AU and GC base pairs have been optimized by DFT method with B3LYP/6-31G(d,p) basis set. The MEP and HOMO-LUMO surfaces have been scanned at 0.001 electron/Bohr3 isodensity surface. Further, HOMO-LUMO energies have been used to calculate ionization potential, electron affinity, electronegativity, global hardness and softness parameters of the drug molecule as well as AU and GC base pairs. IR and Raman spectra of the drug molecule have been analyzed in the light of standard data. Results obtained from NBO analysis have been analyzed in terms of the hybridization of atoms and electronic structure of drug molecule. Binding patterns of the drug molecule with nucleic acid base pairs (AU and GC) have been examined using second order perturbation theory valid at intermediate range. Efforts have been made to elucidate the chemical and biological properties of the drug. The inhibition activity of the drug molecule against HIV-1 reverse transcriptase (Y2NG) in complex with inhibitor GSK560 has been examined with the help of molecular docking. It has been observed that nevirapine prefers to bind in the guanine-cytosine rich region of nucleic acid helices. Further, there exists gross similarity between calculated vibrational assignment and the standard data as reported in the literature. [ABSTRACT FROM AUTHOR]

Boceprevir drug is a ketoamide serine protease inhibitor with a linear peptidomimetic structure that exhibits inhibition activity against 2019-nCoV main protease. This paper reports electronic properties of boceprevir and its molecular docking as well as molecular dynamics simulation analysis with protein receptor. For this, the equilibrium structure of boceprevir has been obtained by DFT at B3LYP and ωB97XD levels with 6-311+G(d,p) basis set in gas and water mediums. HOMO-LUMO and absorption spectrum analysis have been used to evaluate the boceprevir's toxicity and photosensitivity, respectively. Molecular docking simulation has been performed to test the binding affinity of boceprevir with 2019-nCoV M PRO ; which rendered a variety of desirable binding locations between the ligand and target protein's residue positions. The optimum binding location has been considered for molecular dynamics simulation. The findings have been addressed to clarify the boceprevir drug efficacy against the 2019-nCoV M PRO ., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)