Ajay Kumar

Acyclovir, a widely used antiviral medication, is primarily known for its efficacy against viral infections caused by the herpes simplex virus and varicella‐zoster virus. While acyclovir‘s direct effects on viral DNA replication are well‐established, its potential interactions with hormone receptors and influence on hormone functioning remain relatively unexplored. This study employs computational study to investigate the hypothetical relationship between acyclovir and hormone activity. By utilizing DFT studies and NBO analysis, the interaction between acyclovir and hormones is assessed. The results show an increase in the dipole moment of complexes, and drug‐hormone complex conformation may be stabilised by hydrogen bonding. The computed ▵E of the complexes is found to be lesser than the hormone that improved the reactivity of the complexes. From the IR spectra analysis, the formation of hormones and their complexes with acyclovir is analysed.

The major issue with active pharmaceutical ingredients (APIs) is their slow dissolution rate and solubility. This makes them less likely to get into the body and less bioavailable. About 40 % of the drugs already on the market and 90 % being made have APIs that do not dissolve well in water. To deal with this problem, authors have designed eutectic mixture (EMs) of different drugs (danazol, griseofulvin, mefenamic acid, tolfenamic acid and tadalafil) with zinc chloride; studied their interaction and thermodynamic parameters using Density Functional Theory (DFT) computation. DFT calculations confirm an increase in the dipole moment of their EMs in comparison of APIs alone which increases the solubility. The change in Gibbs free energy of formation of EMs in the gaseous phase shows their feasibility ans stability.

COVID-19 has affected more or less every nation across the world and affected the economy very badly. Infection of this virus in human took the life of millions. We have already faced the first and the second waves of COVID-19 and recently, the nations or humanity is afraid of new strain, that is, OMICRON. Considered to highly infectious than the previous strains. Therefore, the researchers are working to find a promising molecule with no or permissible toxicity. In the present work, authors have chosen 10 molecules including the molecules used in curing the infection from nCoV. All the molecules were docked against Mpro of nCoV using iGemdock, a reliable computational tool. Based on the binding energy obtained, it can be seen that only latermovir; remdesivir; zanamivir showed better binding affinity than the gamma oryzanol, the molecule of interest in this work. These three molecules are already in use to cure the patients siffering from the infection of nCoV. But, we need a cost effective and easily available molecule to fight against this viral infection. The binding energy obtained for the formation of complex of gamma oryzanol with Mpro of nCoV through molecular docking is −118.787 kcal/mol. It forms conventional hydrogen bonds with the CYS145 (3.63 Å), LEU141 (6.46 Å) and SER144 (3.18 and 2.87 Å); forms C-H bonds with PHE140 (5.08 Å), pi-alkyl interactions with CYS145 (6.72 Å); forms alkyl interaction with PRO168 (4.08 and 6.88 Å), ALA191 (5.04 Å), LEU141 (5.96 and 6.14 Å). One interesting information is obtained that the value of log Kp of gamma oryzanol is least means more permeable to skin in comparison of other molecules used in the work. Gamma oryzanol in known for to its biological potency like it can modulate the oxidative stress as well as inflammation. DFT calculations of gamma oryzanol (GO) was made at different temperature and no change in the delocalization of electron density as well no change in free energy is observed. Molecular dynamics (MD) simulations of gamma oryzanol with the Mpro of nCoV at different temperatures was performed. The formation of the complex between GO and Mpro of CoV at 290 K, 300 K, 310 K and 320 K for 100 ns was investigated. It has been observed that the effective binding is observed at 290 K, therefore, it can be said that the inhibition of the Mpro of nCoV with GO is maximum at 290 K. Graphical Abstract Communicated by Ramaswamy H. Sarma

COVID-19 has threatened the existence of humanity andthis infection occurs due to SARS-CoV-2 or novel coronavirus, was first reported in Wuhan, China. Therefore, there is a need to find a promising drug to cure the people suffering from the infection. The second wave of this viral infection was shaking the world in the first half of 2021. Drugs Controllers of India has allowed the emergency use of 2-deoxy-D-glucose (2DG) in 2021 for patients suffering from this viral infection. The potentiality of 2-deoxy-D-glucose to intervene in D-glucose metabolism exists and energy deprivation is an effective parameter to inhibit cancer cell development. Once 2DG arrives in the cells, it becomes phosphorylated to 2-deoxy-D-glucose-6-phosphate (2-DG6P), a charged molecule expressively captured inside the cells. On the other hand, 2DG lacks the ability to convert into fructose-6-phosphate, resulting in a hampering of the activity of both glucose-6-phosphate isomerase and hexokinase, and finally causing cell death. Hence, the potential and effectiveness of 2DG with the main protease (Mpro) of novel coronavirus (nCoV) should be investigated using the molecular docking and molecular dynamics (MD) simulations. The ability of 2DG to inhibit the Mpro of nCoV is compared with 2-deoxyglucose (2DAG), an acyclic molecule, and 2-deoxy-D-ribose (2DR). The binding energy of the molecules with the Mpro of nCoV is calculated using molecular docking and superimposed analysis data is obtained. The binding energy of 2DG, 2DR and 2DAG was −2.40, −2.22 and −2.88 kcal/mol respectively. Although the molecular docking does not provide reliable information, therefore, the binding affinity can be confirmed by molecular dynamics simulations. Various trajectories such as Rg, RMSD, RMSF, and hydrogen bonds are obtained from the molecular dynamics (MD) simulations. 2DG was found to be a better inhibitor than the 2DAG and 2DR based on the results obtained from the MD simulations at 300 K. Furthermore, temperature-dependent MD simulations of the Mpro of nCoV with promising 2DG was performed at 295, 310 and 315 K, and the effective binding with the Mpro of nCoV occurred at 295 K. With the use of DFT calculations, optimized geometry and localization of electron density of the frontier molecular orbitals were calculated.

Deep eutectic solvents (DESs) are the mixture of a hydrogen bond donor (HBD) and a hydrogen bond acceptor (HBA) in a particular equivalent ratio. They gained popularity because of low melting point and green (non‐toxic) in nature. DESs showed promising ability as solvents and found to be better than traditional organic solvents and ionic liquids. They are being explored solvents in organic synthesis, substance dissolution, corrosion inhibition, biofuel generation, SO₂/CO₂ absorption, and extraction. In the present work, thioazolidine‐2,4‐dione (T) is taken as hydrogen bond donor, and zinc chloride (Z) is taken as hydrogen bond acceptor. Nine DESs are created using T and Z having different equivalent ratio. Further, they were studied using density functional theory (DFT) approach in gaseous state at different temperatures. T4Z1 found to most soluble in water as the dipole moment is maximum. Free energy of T1Z4 found to be least so may be most stable among all. Further, on changing the temperature from 298 to 323 K and then to 348 K, thermodynamic parameters are determined. Further, the change in free energy for the formation of the DESs are calculated in Hartree per particle as well in kcal/mol. At 298 K, the change in free energy for the formation of T2Z3 is minimum and indicates it feasibility or spontaneity at this temperature. But at temperature of 323 K, T1Z4 and T2Z3 are found to be same. Further, on increasing temperature to 348 K, the change in free energy for T1Z4 and T2Z3 is same and minimum. It means on changing the temperature, the spontaneity for the formation of DES changes. Based on the method of Jakob et al., it can be seen that the temperature changes with the change in composition, that is, the ratio of HBD and HBA. The composition of HBD and HBA is 1:2 and is called deep eutectic mixture as the melting temperature observed is least. There is not a complete agreement between the results obtained by DFT calculations and Jakob et al method.