Functionalized Fullerene for Inhibition of SARS-CoV-2 Variants.

As virus outbreaks continue to pose a challenge, a nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading to virus inhibition. Similarly, hydrophobic C fullerene can prevent virus infection via interactions with hydrophobic cavities of surface proteins.

Rational design of amphiphilic fluorinated peptides: evaluation of self-assembly properties and hydrogel formation.

Advanced peptide-based nanomaterials composed of self-assembling peptides (SAPs) are of emerging interest in pharmaceutical and biomedical applications. The introduction of fluorine into peptides, in fact, offers unique opportunities to tune their biophysical properties and intermolecular interactions. In particular, the degree of fluorination plays a crucial role in peptide engineering as it can be used to control the characteristics of fluorine-specific interactions and, thus, peptide conformation and self-assembly.

Ultra-high permeable phenine nanotube membranes for water desalination.

Nanopore desalination technology hinges on high water-permeable membranes which, at the same time, block ions efficiently. In this study, we consider a recently synthesized [, 151-155 (2019)] phenine nanotube (PNT) for water desalination applications. Using both equilibrium and non-equilibrium molecular dynamics simulations, we show that the PNT membrane completely rejects salts, but permeates water at a rate which is an order-of-magnitude higher than that of all the membranes used for water filtration.

Charge Matters: Mutations in Omicron Variant Favor Binding to Cells.

Evidence is strengthening to suggest that the novel SARS-CoV-2 mutant Omicron, with its more than 60 mutations, will spread and dominate worldwide. Although the mutations in the spike protein are known, the molecular basis for why the additional mutations in the spike protein that have not previously occurred account for Omicron's higher infection potential, is not understood. We propose, based on chemical rational and molecular dynamics simulations, that the elevated occurrence of positively charged amino acids in certain domains of the spike protein (Delta: +4; Omicron: +5 vs.

Role of entropy in determining the phase behavior of protein solutions induced by multivalent ions.

Recent experiments have reported lower critical solution temperature (LCST) phase behavior of aqueous solutions of proteins induced by multivalent ions, where the solution phase separates upon heating. This phenomenon is linked to complex hydration effects that result in a net entropy gain upon phase separation. To decipher the underlying molecular mechanism, we use all-atom molecular dynamics simulations along with the two-phase thermodynamic method for entropy calculation.

Fine-tuning the DNA conductance by intercalation of drug molecules.

In this work we study the structure-transport property relationships of small ligand intercalated DNA molecules using a multiscale modeling approach where extensive ab initio calculations are performed on numerous MD-simulated configurations of dsDNA and dsDNA intercalated with two different intercalators, ethidium and daunomycin. DNA conductance is found to increase by one order of magnitude upon drug intercalation due to the local unwinding of the DNA base pairs adjacent to the intercalated sites, which leads to modifications of the density of states in the near-Fermi-energy region of the ligand-DNA complex. Our study suggests that the intercalators can be used to enhance or tune the DNA conductance, which opens new possibilities for their potential applications in nanoelectronics.

Polysulfates Block SARS-CoV-2 Uptake through Electrostatic Interactions*.

Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with an IC of 67 μg mL (approx.

Concerted Interactions between Multiple gp41 Trimers and the Target Cell Lipidome May Be Required for HIV-1 Entry.

The HIV-1 envelope glycoprotein gp41 mediates the fusion between viral and host cell membranes leading to virus entry and target cell infection. Despite years of research, important aspects of this process such as the number of gp41 trimers involved and how they orchestrate the rearrangement of the lipids in the apposed membranes along the fusion pathway remain obscure. To elucidate these molecular underpinnings, we performed coarse-grained molecular dynamics simulations of HIV-1 virions pinned to the CD4 T cell membrane by different numbers of gp41 trimers.

Understanding enhanced mechanical stability of DNA in the presence of intercalated anticancer drug: Implications for DNA associated processes.

Most of the anticancer drugs bind to double-stranded DNA (dsDNA) by intercalative-binding mode. Although experimental studies have become available recently, a molecular-level understanding of the interactions between the drug and dsDNA that lead to the stability of the intercalated drug is lacking. Of particular interest are the modifications of the mechanical properties of dsDNA observed in experiments.

Unfolding Dynamics of Ubiquitin from Constant Force MD Simulation: Entropy-Enthalpy Interplay Shapes the Free-Energy Landscape.

Force probe methods are routinely used to study conformational transitions of biomolecules at single-molecule level. In contrast to simple kinetics, some proteins show complex response to mechanical perturbations that is manifested in terms of unusual force-dependent kinetics. Here, we study, via fully atomistic molecular dynamics simulations, constant force-induced unfolding of ubiquitin protein.

Translocation of Bioactive Molecules through Carbon Nanotubes Embedded in the Lipid Membrane.

One of the major challenges of nanomedicine and gene therapy is the effective translocation of drugs and genes across cell membranes. In this study, we describe a systematic procedure that could be useful for efficient drug and gene delivery into the cell. Using fully atomistic molecular dynamics (MD) simulations, we show that molecules of various shapes, sizes, and chemistries can be spontaneously encapsulated in a single-walled carbon nanotube (SWCNT) embedded in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer, as we have exemplified with dendrimers, asiRNA, ssDNA, and ubiquitin protein.

The SPL7013 dendrimer destabilizes the HIV-1 gp120-CD4 complex.

The poly (l-lysine)-based SPL7013 dendrimer with naphthalene disulphonate surface groups blocks the entry of HIV-1 into target cells and is in clinical trials for development as a topical microbicide. Its mechanism of action against R5 HIV-1, the HIV-1 variant implicated in transmission across individuals, remains poorly understood. Using docking and fully atomistic MD simulations, we find that SPL7013 binds tightly to R5 gp120 in the gp120-CD4 complex but weakly to gp120 alone.