Modelling the DFT structural and reactivity study of feverfew and evaluation of its potential antiviral activity against COVID-19 using molecular docking and MD simulations.

Abstract: The unavailability of a proper drug against SARS-CoV-2 infections and the emergence of various variants created a global crisis. In the present work, we have studied the antiviral behavior of feverfew plant in treating COVID-19. We have reported a systematic in silico study with the antiviral effects of various phytoconstituents Borneol (C10H18O), Camphene (C10H16), Camphor (C10H16O), Alpha-thujene (C10H16), Eugenol (C10H14O), Carvacrol (C10H14O) and Parthenolide (C15H20O3) of feverfew on the viral protein of SARS-CoV-2. Parthenolide shows the best binding affinity with both main protease (Mpro) and papain-like protease (PLpro). The molecular electrostatic potential and Mulliken atomic charges of the Parthenolide molecule shows the high chemical reactivity of the molecule. The docking of Parthenolide with PLpro give score of -8.0 kcal/mol that validates the good binding of Parthenolide molecule with PLpro. This complex was further considered for molecular dynamics simulations. The binding energy of the complex seems to range in between -3.85 to -11.07 kcal/mol that is high enough to validate the stability of the complex. Free energy decomposition analysis have been also performed to understand the contribution of residues that reside into the binding site. Good binding affinity and reactivity response suggested that Parthenolide can be used as a promising drug against the COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02067-6.

DFT and MD simulation investigation of favipiravir as an emerging antiviral option against viral protease (3CLpro) of SARS-CoV-2.

As per date, around 20 million COVID-19 cases reported from across the globe due to a tiny 125 nm sized virus: SARS-CoV-2 which has created a pandemic and left an unforgettable impact on our world. Besides vaccine, medical community is in a race to identify an effective drug, which can fight against this disease effectively. Favipiravir (F) has recently attracted too much attention as an effective repurposed drug against COVID-19. In the present study, the pertinency of F has been tested as an antiviral option against viral protease (3CLpro) of SARS-CoV-2 with the help of density functional theory (DFT) and MD Simulation. Different electronic properties of F such as atomic charges, molecular electrostatic properties (MEP), chemical reactivity and absorption analysis have been studied by DFT. In order to understand the interaction and stability of inhibitor F against viral protease, molecular docking and MD simulation have been performed. Various output like interaction energies, number of intermolecular hydrogen bonding, binding energy etc. have established the elucidate role of F for the management of CoV-2 virus for which there is no approved therapies till now. Our findings highlighted the need to further evaluate F as a potential antiviral against SARS-CoV-2.

Neuroprotective immunity by essential nutrient "Choline" for the prevention of SARS CoV2 infections: An in silico study by molecular dynamics approach.

Prenatal COVID infection is one of the worst affected and least attended aspects of the COVID-19 disease. Like other coronaviruses, CoV2 infection is anticipated to affect fetal development by maternal inflammatory response on the fetus and placenta. Studies showed that higher prenatal choline level in mother's body can safeguard the developing brain of the fetus from the adverse effects of CoV2 infection. Choline is commonly used as food supplement. By virtual screening, molecular docking and molecular dynamics techniques, we have established a strong inhibitory possibility of choline for SARS 3CLpro protease which may provide a lead for prenatal COVID-19 treatment.

White light generation by carbonyl based indole derivatives due to proton transfer: an efficient fluorescence sensor.

The motivation of the present work is to understand the optical, chemical, and electrical aspects of the proton transfer mechanism of indole (I) and some carbonyl based indole derivatives: indole-3-carboxaldehyde (I3C) and indole-7-carboxaldehyde (I7C) for both powder form and their liquid solution. Structural information for indole derivatives (isolated molecule and in solution) is obtained with density functional theory (DFT) and time dependent DFT (TD-DFT) methods. Calculated transition energies are used to generate UV-vis, FTIR, Raman, and NMR spectra which are later verified with the experimental spectra. The occurrence of different conformers [cis (N(c)), trans (N(t)), and zwitterion (Z*)] have been interpreted by Mulliken charge, natural bond orbital (NBO) analysis, and polarization versus electric field (P-E loop) studies. (1)H and (13)C NMR and molecular vibrational frequencies of the fundamental modes established the stability of Nc due to the presence of intramolecular hydrogen bonding (IHB) in the ground state (S0). Computed/experimental UV-vis absorption/emission studies reveal the creation of new species: zwitterion (Z*) and anion (A*) in the excited state (S1) due to excited state intramolecular and intermolecular proton transfer (ESI(ra)PT and ESI(er)PT). Increased electrical conductivity (σ(ac)) with temperature and increased ferroelectric polarization at higher field verifies proton conduction in I7C.

Virtual screening of truncated single stranded DNA aptamers for Staphylococcal enterotoxin type A.

Single stranded DNA (ssDNA)/RNA aptamers, are screened through the labor intensive, iterative Systematic Evolution of Ligand by Exponential Enrichment process (SELEX) method. Complete sequence of screened aptamers never interacts with target or participates in final structure. Hence, in silico tools can be used to redesign a short length aptamer from previously reported aptamers which can have high affinity and specificity to the target. This approach is fast, cost effective, and less laborious than in vitro SELEX towards finding an aptamer sequence with better affinity with the target. Here, Staphylococcal enterotoxin type A (SEA) was used as target. A total of nine aptamers reported for different Staphylococcal food poisoning (SFP) enterotoxins were used as a starting pool. The aptamers were variously truncations and thoroughly analyzed through in silico methods. Three truncated aptamers namely AptSEA1.4, AptSEA2.4 and AptSEA8.4 were found to show higher affinity with target SEA. The computational data was also validated with DOT BLOT assay complemented with image analysis. These results also confirmed that the % specific binding and the dissociation constant (Kd) of truncated aptamers AptSEA1.4, AptSEA2.4 and AptSEA8.4 was better than their original counterparts. The truncated aptamers showed great promise to be used as a capture reagent in developing a sensitive assay for detection of SEA.Communicated by Ramaswamy H. Sarma.

Raman and X-ray investigations of ferroelectric phase transition in NH4HSO4.

Temperature-dependent Raman spectroscopy and X-ray diffraction studies have been carried out on NH(4)HSO(4) single crystals in the temperature range 77-298 K. Two structural transitions driven by the molecular ordering and change in crystal symmetries are observed below 263 and 143 K. These phase transitions are marked by the anomalies in the temperature dependence of wavenumber and fwhm of several internal vibrational modes. The Raman spectra and X-ray data enable us to understand the nature of the molecular ordering resulting in the ferroelectric phase below 263 K, sandwiched between two nonferroelectric phases. The crystal structure of the ferroelectric phase is determined correctly as Pc, which has been earlier solved in Ba symmetry. The temperature dependent Raman and X-ray results suggest that the disorder to order transition leading to lower symmetry below 263 K is driven by the change in HSO(4)(-) ions and that below 143 K is driven by the change in both HSO(4)(-) and NH(4)(+) ions.

Effectivity of repurposed drugs against SARS-CoV-2 infections, A hope for COVID 19: inhibitor modelling studies by docking and molecular dynamics.

In the present study, we have done a comparative study on the efficacy of some currently used repurposed drugs: Oseltamivir (O), Favipiravir (F) and Hydroxychloroquine (H) in individual and in their combinational mode against CoV-2 infections. The ADME analysis has helped us to identify the inhibitory possibility of the tested drugs towards receptor 3CLpro protein of SARS-CoV-2. Various thermodynamical parameters obtained from Molecular Docking, Molecular dynamics (MD) and MMPBSA simulations like binding affinity, potential energy (Epot), RMSD, RMSF, SASA energy, interaction energies, Gibbs free energy (ΔGbind) etc. also helped us to verify the effectivity of mentioned drugs against CoV-2 protease.

In silico investigation of phytoconstituents from Indian medicinal herb 'Tinospora cordifolia (giloy)' against SARS-CoV-2 (COVID-19) by molecular dynamics approach.

The recent appearance of COVID-19 virus has created a global crisis due to unavailability of any vaccine or drug that can effectively and deterministically work against it. Naturally, different possibilities (including herbal medicines having known therapeutic significance) have been explored by the scientists. The systematic scientific study (beginning with in silico study) of herbal medicines in particular and any drug in general is now possible as the structural components (proteins) of COVID-19 are already characterized. The main protease of COVID-19 virus is Mpro or 3CLpro which is a key CoV enzyme and an attractive drug target as it plays a pivotal role in mediating viral replication and transcription. In the present study, 3CLpro is used to study drug:3CLpro interactions and thus to investigate whether all or any of the main chemical constituents of Tinospora cordifolia (e.g. berberine (C20H18NO4), ß-sitosterol (C29H50O), coline (C5H14NO), tetrahydropalmatine (C21H25NO4) and octacosanol (C28H58O)) can be used as an anti-viral drug against SARS-CoV-2. The in silico study performed using tools of network pharmacology, molecular docking including molecular dynamics have revealed that among all considered phytochemicals in Tinospora cordifolia, berberine can regulate 3CLpro protein's function due to its easy inhibition and thus can control viral replication. The selection of Tinospora cordifolia was motivated by the fact that the main constituents of it are known to be responsible for various antiviral activities and the treatment of jaundice, rheumatism, diabetes, etc.Communicated by Ramaswamy H. Sarma.

Computational study of the intermolecular interactions and their effect on the UV-visible spectra of the ternary liquid mixture of benzene, ethanol and propylene glycol.

Quantum chemical calculations are well-equipped to provide answers to the questions regarding the different aspects of intermolecular interactions. We investigate the benzene, ethanol and 1,2 propanediol ternary mixture with theoretical as well as experimental UV-Vis spectroscopy. An extensive theoretical study on the molecular structure and UV-Vis spectral analysis was undertaken using density functional theory (DFT) method. Structural parameter analysis and the HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) energy gap help to describe the possible interaction between molecules in dimer and in combination. Interaction energy has been calculated from topological study. Time-dependent density functional theory (TDDFT) calculations on dimer/cluster in gas phase help to understand the effect of the molecular interaction on the overall spectral shift and related intensity variation. Our results show that in the ternary mixture, the interaction energies of the interactions are π-π interaction: 0.52-2.57 kcal/mol, Hp-π interaction: 1.15 kcal/mol and H-bonding: 2.49 to 4.46 kcal/mol. The π-π interaction and H-bonding cause red shift in absorption spectra while Hp-π interaction causes blue shift. In the ternary mixture, the strength of different kinds of interaction depends on the concentration, and as each interaction has its own effect on spectral shift, the overall experimental spectra get broader and distorted from the Gaussian shape.

Perturbation of hydrogen bonding in hydrated pyrrole-2-carboxaldehyde complexes.

The interaction of external water molecules with hydrated pyrrole-2-carboxaldehyde PCL/(H2O) n complexes was investigated. The work was supported by both theoretical [DFT/TD-DFT methods using 6-311G++(d,p) basis set in the ground (S0) and excited (S1, S2, S3)states] and experimental [UV-Vis, FTIR and Raman] verification. The focus of the present work was on the weak intermolecular O-H⋯O, N-H⋯O-H hydrogen bonded interaction (IerHB) between PCL and external water molecules, and the influence of increasing the number of water molecules to form hydrated PCL/(H2O)n complexes. Effects were observed on different vibrational normal modes and on electronic transition levels. A hydrogen-bonded network of water induces a shift to higher energy in certain normal modes of PCL to form stable PCL/(H2O)n complexes by lowering the barrier energy. Potential energy distribution (PED) analysis indicates a significant charge transfer from PCL to water by creating a water bridge. Hydrogen bonding effects account for the substantial red shift and broadness in νNH, νCO vibrational modes. Water rearrangement turns out to be the main driving force for hydrated complex formation. Graphical abstract Stability of PCL/(H2O)4 hydarted complex.

Effects of hydrogen bonding between pyrrole-2-carboxaldehyde and nearest polar and nonpolar environment.

The present paper represents dominant effects of hydrogen bonding on the existence of different molecular aggregates in one of the heterocyclic pyrrole system: pyrrole-2-carboxaldehyde (PCL). Theoretical and experimental Raman spectral evidence verifies the existence of different molecular aggregates like dimeric, monomeric, hydrated complex states in PCL. Atoms in molecules (AIMs) analysis and fluorescence decay profile provide a strong signature of intermolecular hydrogen bonding (IerHB) as the possible reason for the existence of cis form of dimeric (X) molecular aggregates. The high remnant polarization of 3.13µCcm-2 and smaller dielectric loss in solid form of PCL arise due to in X by ordering of dipoles as a result of IerHB. A remarkable high ferroelectric response in solid phase makes PCL a desirable candidate to be used as raw material for energy storage devices. For solution phase, in presence of external hydroxylic environment, PCL reacts with external water molecules through weak IerHB and creates different hydrated PCL/(H2O)n complexes by creating water bridge with number of water molecules from 1 to n. An increasing number of water molecules helps to form stronger hydrated complex by separation of charges by lowering the transferring energy barrier.

Photophysical behaviour of 4-(imidazole-1-yl) phenol and its complexation with beta-cyclodextrin in ground and excited states.

This paper mainly dwells on photophysics of 4-(imidazole-1-yl) phenol (IDP) in different solvents and temperatures from the investigations of absorption, emission and laser flash photolysis and also on the nature of complexation with beta-cyclodextrin (CD) in ground and excited states. IDP makes 1:1 inclusion complex with beta-CD in ground, excited singlet and also in triplet states. The orientation of complex could be ascertained as imidazole moiety stays inside the cavity with phenol moiety stays in the bulk. A proposed energy level scheme unveils that vibronic interaction and spin-orbit interaction are found to be active differently in aprotic and protic solvents.

Excited state behavior of pyrrole 2-carboxyldehyde: theoretical and experimental study.

Photophysical and photochemical dynamics of excited state proton transfer reaction have been reported for Pyrrole 2-carboxyldehyde (PCL). Experimental and theoretical observations yield all possible signatures of intramolecular and intermolecular proton transfer in an excited state. Dual emission (~325 nm, ~375 nm) on photo excitation indicates the existence of more than one species in an excited state. Computed reaction pathway and two-dimensional potential energy profile in the ground state reveals a single minimum corresponding to normal form (E). Dual minima in excited state energy profile shows the existence of two species, one normal and other zwitterionic (Z*) species. A large Stokes shifted emission at ~375 nm in hydrocarbon medium reveals the existence of zwitterionic species due to Excited state intramolecular proton transfer (ESI(ra)PT). Excited State Intermolecular proton transfer (ESI(er)PT) is observed in a hydroxylic environment around 430-490 nm. pH variation in hydroxylic medium suggests the formation of anion (A((-))) from Z*.