Non-Toxic Dimeric Peptides Derived from the Bothropstoxin-I Are Potent SARS-CoV-2 and Papain-like Protease Inhibitors

The COVID-19 outbreak has rapidly spread on a global scale, affecting the economy and public health systems throughout the world. In recent years, peptide-based therapeutics have been widely studied and developed to treat infectious diseases, including viral infections. Herein, the antiviral effects of the lysine linked dimer des-Cys¹¹, Lys¹²,Lys¹³-(pBthTX-I)₂K ((pBthTX-I)₂K)) and derivatives against SARS-CoV-2 are reported. The lead peptide (pBthTX-I)₂K and derivatives showed attractive inhibitory activities against SARS-CoV-2 (EC₅₀ = 28–65 µM) and mostly low cytotoxic effect (CC₅₀ > 100 µM). To shed light on the mechanism of action underlying the peptides’ antiviral activity, the Main Protease (M^pro) and Papain-Like protease (PL^pro) inhibitory activities of the peptides were assessed. The synthetic peptides showed PL^pro inhibition potencies (IC₅₀s = 1.0–3.5 µM) and binding affinities (K_d = 0.9–7 µM) at the low micromolar range but poor inhibitory activity against M^pro (IC₅₀ > 10 µM). The modeled binding mode of a representative peptide of the series indicated that the compound blocked the entry of the PL^pro substrate toward the protease catalytic cleft. Our findings indicated that non-toxic dimeric peptides derived from the Bothropstoxin-I have attractive cellular and enzymatic inhibitory activities, thereby suggesting that they are promising prototypes for the discovery and development of new drugs against SARS-CoV-2 infection.     

Synergistic effect of nanoionic destabilization and partial dehydrogenation for enhanced ionic conductivity in MBH4-C60 (M = Li+, Na+) nanocomposites

Journal of Solid State Electrochemistry - In this work, we evaluate the electrochemical properties of MBH4-C60 (M = Li+, Na+) nanocomposites for potential use as a solid-state electrolyte in...     

Hybrid EuIII Coordination Luminophore Standing on Two Legs on Silica Nanoparticles for Enhanced Luminescence

In this study, we have demonstrated a two-legged, upright molecular design method for monochromatic and bright red luminescent Ln^III-silica nanomaterials. A novel Eu^III-silica hybrid nanoparticle was developed by using a doubly binding TPPO−Si(OEt)₃ (TPPO: triphenyl phosphine oxide) linker. The TPPO−Si(OEt)₃ was confirmed by ¹H, ³¹P, ²⁹Si NMR spectroscopy and single-crystal X-ray analysis. Luminescent Eu(hfa)₃ and Eu(tfc)₃ moieties (hfa: hexafluoroacetylacetonate, tfc: 3-(trifluoromethylhydroxymethylene)camphorate) were fixed onto TPPO−Si(OEt)₃-modified silica nanoparticles, producing Eu(hfa)₃(TPPO−Si)₂-SiO₂ and Eu(tfc)₃(TPPO−Si)₂-SiO₂, respectively. Eu(hfa)₃(TPPO−Si)₂−SiO₂ exhibited the higher intrinsic luminescence quantum yield (93 %) and longer emission lifetime (0.98 ms), which is much larger than those of previously reported Eu^III-based hybrid materials. Eu(tfc)₃(TPPO−Si)₂−SiO₂ showed an extra-large intrinsic emission quantum yield (54 %), although the emission quantum yield for the precursor Eu(tfc)₃(TPPO−Si(OEt)₃)₂ was found to be 39 %. These results confirmed that the TPPO−Si(OEt)₃ linker is a promising candidate for development of Eu^III-based luminescent materials.     

Synthesis of (±)-1-(2,6,6-trimethyl-4-hydroxycyclohexenyl)-1,3-butanedione (1), a marine natural product

A short synthesis of racemic natural product (1) from the known compound (7) is described. A model study, using cyclochexanone as starting material, is also reported.     

Electron binding energies of anionic magnesium clusters and the nonmetal-to-metal transition

The binding energies of the two most external electrons in Mg- n, n=2-22, clusters are computed using the gradient-corrected density functional theory and a new scheme for converting the Kohn-Sham eigenenergies into electron removal energies. The computations are performed for the anionic clusters considered in the most stable configurations of both Mg- n and Mg n. The results are compared with photoelectron spectroscopy data [O. C. Thomas, following Letter, Phys. Rev. Lett. 89, 213403 (2002)]], and their implications for the finite-size analog of the nonmetal-to-metal transition are analyzed.     

Mixing of non-Newtonian fluids in steadily forced systems

We investigate mixing in a viscoelastic and shear-thinning fluid-a very common combination in polymers and suspensions. We find that competition between elastic and viscous forces generates self-similar mixing, lobe transport, and other characteristics of chaos. The mechanism by which chaos is produced is evaluated both in experiments and in a simple model. We find that chaotic flow is generated by spontaneous oscillations, the magnitude and frequency of which govern the extent of chaos and mixing.     

Existence of Baryons,Baryon Spectrum and Mass Splitting in Strong Coupling Lattice QCD

We consider a functional integral formulation for one-flavor lattice Quantum Chromodynamics in d=2,3 space dimensions and imaginary time, and work in the regime of the small hopping parameter , and zero plaquette coupling. Following the standard construction, this model exhibits positivity which is used to obtain the underlying physical Hilbert space . Then, using a Feynman-Kac formalism, we write the correlation functions for the model as functional integrals over the space of Grassmannian (fermionic) fields for one quark specie and the SU(3) gauge fields. We determine the energy-momentum spectrum associated with gauge invariant local baryon (anti-baryon) fields which are composites of three quark (anti-quark) fields. With the associated correlation functions, we establish a Feynman-Kac formula, and a spectral representation for the Fourier transform of the two-point functions. This representation allows us to show that baryons and anti-baryons arise as tightly bound, bound states of three (anti-)quarks. Labelling the components of the baryon fields by s=3/2,1/2,-1/2,-3/2, we show that the baryon and anti-baryon mass spectrum only depends on |s|, and the associated masses are given by M_s= –3ln+r_s(), where r_s() is real analytic in , for each d=2,3. The mass splitting is M_3/2–M_1/2=18⁶, for d=2 and, if any, is at least of (⁷), for d=3. In the subspace _o generated by an odd number of fermions, the baryon and anti-baryon energy-momentum dispersion curves are isolated up to near the baryon-meson threshold –5ln (upper gap property), identical and are determined up to (⁵). The symmetries of coordinate reflections, spatial lattice rotations, parity and charge conjugation are established for the correlation functions, and are shown to be implemented on by unitary (anti-unitary, for time reversal) operators.     

Low field intermolecular double-quantum coherence imaging via the Overhauser effect

Intermolecular double-quantum coherence (i-DQC) signals in liquids are usually associated with high magnetic fields. We demonstrate that, in a magnetic field of only 16mT, i-DQC imaging of water protons is feasible thanks to the nuclear magnetization enhancement produced by the Overhauser effect. i-DQC images of a phantom containing an aqueous solution of a trityl free radical, with phase encoding in the DQC evolution period or in the acquisition period, are presented. Possible applications of low field i-MQC images are proposed.     

Differential Simplicity in Polynomial Rings and Algebraic Independence of Power Series

Let k be a field of characteristic zero, f(X,Y), g(X,Y)k[X,Y],g(X,Y) (X,Y) and d:=g(X,Y)/X + f(X,Y)/Y. A connection is establishedbetween the d-simplicity of the local ring k[X,Y]_(X,Y) and thetranscendency of the solution in tk[[t]] of the algebraic differentialequation g(t,y(t))·(/t)y(t)+f(t,y(t)). This connectionis used to obtain some interesting results in the theory ofthe formal power series and to construct new examples of differentiallysimple rings.     

Holomorphic K-Theory, Algebraic Co-cycles, and Loop Groups

In this paper we study the holomorphic K-theory of a projective variety. This K-theory is defined in terms of the homotopy type of spaces of holomorphic maps from the variety to Grassmannians and loop groups. This theory is built out of studying algebraic bundles over a variety up to algebraic equivalence. In this paper we will give calculations of this theory for flag like varieties which include projective spaces, Grassmannians, flag manifolds, and more general homogeneous spaces, and also give a complete calculation for symmetric products of projective spaces. Using the algebraic geometric definition of the Chern character studied by the authors we will show that there is a rational isomorphism of graded rings between holomorphic K-theory and the appropriate morphic cohomology groups, in terms of algebraic co-cycles in the variety. In so doing we describe a geometric model for rational morphic cohomology groups in terms of the homotopy type of the space of algebraic maps from the variety to the symmetrized loop group U(n)/ _n where the symmetric group _n acts on U(n) via conjugation. This is equivalent to studying algebraic maps to the quotient of the infinite Grassmannians BU(k) by a similar symmetric group action. We then use the Chern character isomorphism to prove a conjecture of Friedlander and Walker stating that if one localizes holomorphic K-theory by inverting the Bott class, then rationally this is isomorphic to topological K-theory. Finally this will allows us to produce explicit obstructions to periodicity in holomorphic K-theory, and show that these obstructions vanish for generalized flag mani-folds.