Chemical Physics Letters

Herein, we investigate the influence of aspect ratio and quantum confinement on the single-photon (σ1 ) and two-photon absorption cross-section (σ2 ) for perovskite CsPbI3 nanorod (NR). Notably, experimentally measured data show extremely high σ2 for CsPbI3 NR (10.8 × 107 GM) which is five orders of magnitude higher than organic chromophores, and two order of magnitude higher than CsPbBr3 nanocrystals. Moreover, σ2 for NRs can be enhanced by two-orders of magnitude by varying the aspect ratio and σ1 enhances linearly with aspect ratios...

Coarse-grained molecular dynamics simulations of the lipid bilayer mixture of POPC and cholesterol were carried out in the presence and absence of ganglioside monosialo 1 (GM1) with N - terminal domain (NTD) of SARS-CoV-2 spike glycoprotein. The interactions of GM1 with two different NTD orientations were compared. NTD orientation I compactly bind GM1 predominantly through the sialic acid and the external galactose moieties providing more restriction to GM1 mobility whereas orientation II is more distributed on the lipid surface and due to the relaxed mobility of GM1 there, presumably, the NTD receptor penetrates more through the membrane...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world rapidly, which seriously threatens to human health and safety. The rapid detection of the virus in the early stage is very important to prevent the cross infection and transmission. It is also a key link in the post-treatment examination. This paper has explored the infrared (IR) spectra of spike protein receptor-binding domain (RBD) for SARS-CoV-2 using molecular dynamics simulations, and the absorption bands are assigned...

In order to control COVID-19, rapid and accurate detection of the pathogenic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an urgent task. The target spike proteins of SARS-CoV-2 have been detected experimentally via Raman spectroscopy. However, there lacks high-accuracy theoretical Raman spectra of the spike proteins to as a standard reference for the clinic diagnostic purpose. In this paper, we propose a large fragment method to construct the high-precision Raman spectra for the spike proteins...

The binding of the active form of Remdesivir (RTP) to RNA-dependent RNA Polymerase (RdRp) of SARS-CoV-2 was studied using molecular dynamics simulation. The RTP maintained the interactions observed in the experimental cryo-EM structure. Next, we designed new analogues of RTP, which not only binds to the RNA primer strand in a similar pose as that of RTP, but also binds more strongly than RTP does as predicted by MM-PBSA binding energy. This suggest that these analogues might be able to covalently link to the primer strand as RTP, but their 3' modification would terminate the primer strand growth...

The main protease (Mpro ) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) catalyzes the cleavage of polyproteins for viral replication. Here, large-scale quantum molecular dynamics and metadynamics simulations for ligand-free Mpro were performed, where all the atoms were treated quantum-mechanically, focusing on elucidation of the controversial active-site protonation state. The simulations clarified that the interconverting multiple protonation states exist in unliganded Mpro , and the catalytically relevant ion-pair state is more stable than the neutral state, which is consistent with neutron crystallography...

The SARS-CoV-2 papain-like (PLpro ) protease is essential for viral replication. We investigated potential antiviral effects of hypericin relative to the well-known noncovalent PLpro inhibitor GRL-0617. Molecular dynamics and PELE Monte Carlo simulations highlight favourable binding of hypericin and GRL-0617 to the naphthalene binding pocket of PLpro . Although not potent as GRL-0617 (45.8 vs 1.6µM for protease activity, respectively), in vitro fluorogenic enzymatic assays with hypericin show concentration-dependent inhibition of both PLpro protease and deubiquitinating activities...

Keeping track of a hydrated proton in dynamics simulations is important and nontrivial. Here, we report two revised algorithms for the proton indicator, a pseudo-atom whose position approximates the location of an excess proton diffusing via the Grotthuss mechanism in aqueous solution. The new methods describe the delocalized proton as a structural defect. Encouragingly, in test simulations of a hydrated proton in bulk water, the new algorithms substantially outperform the original scheme by significantly reducing large displacements in the indicator positions upon donor switch, yielding smoother trajectories that effectively track the movement of the solvated proton...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) is a promising target for antiviral drugs. In this study, a chemical library (n = 300) was screened against the nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain. Blind docking was performed using a selection of 30 compounds and nine ligands were chosen based on their docking scores, safety profile, and availability. Using cluster analysis on a 10 microsecond molecular dynamics simulation trajectory (from D...

The main protease (3CLpro) of SARS-CoV and SARS-CoV-2 is a promising target for discovery of novel antiviral agents. In this paper, new possible inhibitors of 3CLpro with high predicted binding affinity were detected through multistep computer-aided molecular design and bioisosteric replacements. For discovery of prospective 3CLpro binders several virtual ligand libraries were created and combined docking was performed. Moreover, the molecular dynamics simulation was applied for evaluation of protein-ligand complexes stability...

One of the promising drug targets against COVID-19 is an RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. The tertiary structures of the SARS-CoV-2 and SARS-CoV RdRps are almost the same. However, the RNA-synthesizing activity of the SARS-CoV RdRp is higher than that of the SARS-CoV-2 RdRp. We performed molecular dynamics simulations and found differences in their dynamic properties. In the SARS-CoV RdRp, motifs A-G, which form the active site, are up to 63% closer to each other. We also observed cooperative domain motion in the SARS-CoV RdRp...

In this study, density functional theory (DFT) and docking calculations were systematically performed to study the non-competitive interaction between Hydroxychloroquine (HCQ) and azithromycin (AZTH). The calculated changes in Gibbs free energy and enthalpy (at 310 K ) were positive, indicating the non-spontaneous formation of HCQ-AZTH specifically in water media. Docking calculation confirmed the obtained DFT result as evident from the different binding sites of both drugs to the SARS-CoV-2 main protease and human angiotensin-converting enzyme 2 (ACE2) proteins...

COVID-19, a new strain of coronavirus family, was identified at the end of 2019 in China. The COVID-19 virus spread rapidly all over the world. Scientists strive to find virus-specific antivirals for the treatment of COVID-19. The present study reports a molecular docking study of the stilbenolignans and SARS-CoV-2 main protease (SARS-CoV-2 Mpro) inhibitors. The detailed interactions between the stilbenolignan analogues and SARS-CoV-2 Mpro inhibitors were determined as hydrophobic bonds, hydrogen bonds and electronic bonds, inhibition activity, ligand efficiency, bonding type and distance and etc...

The SARS-CoV-2 papain-like protease (PLpro ) is a suitable target for drug development, and its deubiquitinating and deISGylating activities have also been reported. In this study, molecular docking was used to investigate the binding properties of a selection of dietary compounds and naphthalene-based inhibitors to the previously characterised binding site of GRL-0617. The structures of the SARS-CoV-2 and SARS-CoV PLpro in complex with interferon-stimulated gene 15 (ISG15) and lysine 48 (K48)-linked diubiquitin were utilised...

A recent screening study highlighted a molecular compound, apilimod, for its efficacy against the SARS-CoV-2 virus, while another compound, tetrandrine, demonstrated a remarkable synergy with the benchmark antiviral drug, remdesivir. Here, we find that because of significantly reduced potential energy barriers, which also give rise to pronounced quantum effects, the rotational dynamics of the most dynamically active methyl groups in apilimod and tetrandrine are much faster than those in remdesivir. Because dynamics of methyl groups are essential for biochemical activity, screening studies based on the computed potential energy profiles may help identify promising candidates within a given class of drugs...

The COVID-19 pandemic caused by SARS-CoV-2 has resulted in an international health emergency. The SARS-CoV-2 nsp16 is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase, and with its cofactor nsp10, is responsible for RNA cap formation. This study aimed to identify small molecules binding to the SAM-binding site of the nsp10-nsp16 heterodimer for potential inhibition of methyltransferase activity. By screening a library of 300 compounds, 30 compounds were selected based on binding scores, side-effects, and availability...

Humans around the globe have been severely affected by SARS-CoV-2 and no treatment has yet been authorized for the treatment of this severe condition brought by COVID-19. Here, an in silico research was executed to elucidate the inhibitory potential of selected thiazolides derivatives against SARS-CoV-2 Protease (Mpro) and Methyltransferase (MTase). Based on the analysis; 4 compounds were discovered to have efficacious and remarkable results against the proteins of the interest. Primarily, results obtained through this study not only allude these compounds as potential inhibitors but also pave the way for in vivo and in vitro validation of these compounds...

SARS-CoV-2 has posed global challenge for healthcare due to COVID-19. The main protease (Mpro ) of this virus is considered as a major target for drug development efforts. In this work, we have used virtual screening approach with molecular dynamics simulations to identify high affinity and low molecular alternatives of boceprevir, a repurposed drug currently being evaluated against Mpro . Out of 180 compounds screened, two boceprevir analogs (PubChem ID: 57841991 and 58606278) were reported as potential alternatives with comparable predicted protease inhibitor potential and pharmacological properties...

The interactions of two crucial proteins of COVID-19 have been investigated with potential antiviral compounds from Moringa oliefera using quantum chemical, molecular docking and dynamic methods. The results of the present investigation show that ellagic acid and apigenin possess the highest binding affinities of -7.1 and -6.5 Kcal.mol-1 against nsp9 and -6.9 and -7.1 Kcal.mol-1 against nsp10, respectively. The dynamic behavior of individual proteins and their respective best docked ligand-protein complexes are also studied at 30ns timescale...

Interactions of hydroxychloroquin (HCQ) with the receptor binding domain (RBD) of SARS-CoV-2 were studied from atomistic simulation and ONIOM techniques. The key-residues of RBD responsible for the human transmission are recognized to be blocked in a heterogeneous manner with the favorable formation of key-residue:HCQ (1:1) complex. Such heterogeneity in binding was identified to be governed by the differential life-time of the hydrogen bonded water network anchoring HCQ and the key-residues. The intermolecular proton transfer facilitates the most favorable Lys417:HCQ complexation...