Point mutations in SARS-CoV-2 variants induce long-range dynamical perturbations in neutralizing antibodies

Monoclonal antibodies are emerging as a viable treatment for the coronavirus disease 19 (COVID-19). However, newly evolved variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can reduce the efficacy of currently available antibodies and can diminish vaccine-induced immunity. Here, we demonstrate that the microscopic dynamics of neutralizing monoclonal antibodies can be profoundly modified by the mutations present in the spike proteins of the SARS-COV-2 variants currently circulating in the world population. The dynamical perturbations within the antibody structure, which alter the thermodynamics of antigen recognition, are diverse and can depend both on the nature of the antibody and on the spatial location of the spike mutation. The correlation between the motion of the antibody and that of the spike receptor binding domain (RBD) can also be changed, modulating binding affinity. Using protein-graph-connectivity networks, we delineated the mutant-induced modifications in the information-flow along allosteric pathway throughout the antibody. Changes in the collective dynamics were spatially distributed both locally and across long-range distances within the antibody. On the receptor side, we identified an anchor-like structural element that prevents the detachment of the antibodies; individual mutations there can significantly affect the antibody binding propensity. Our study provides insight into how virus neutralization by monoclonal antibodies can be impacted by local mutations in the epitope via a change in dynamics. This realization adds a new layer of sophistication to the efforts for rational design of monoclonal antibodies against new variants of SARS-CoV2, taking the allostery in the antibody into consideration.

Mutations in the new variants of SARS-CoV-2 spike protein modulates the dynamics of the neutralizing antibodies. Capturing such modulations from MD simulations and graph network model identifies the role of mutations in facilitating immune evasion.     

Toward reactant encapsulation for substrate-selectivity

A synthetic tris-(bis-(aminomethyl)pyridine) receptor was prepared in excellent yields via reversible imine condensation strategy. Catalytic activity in Henry reactions of the corresponding copper(II) complex was studied. Capitalizing on previous works by Anslyn with related receptors, the dramatic increase in basicity induced by this type of complex on diketo-derivatives was used to perform a nucleophilic addition of a deprotonated substrate onto an electrophile within the cavity. Hence, a Lewis acid stabilized nitronate was reacted with various aldehydes. A notable preference for small reactants easily accommodated in the cavity over encumbered ones was observed, thus representing an example of substrate-selectivity.     

Rate of Convergence of a Stochastic Particle System for the Smoluchowski Coagulation Equation

By continuing the probabilistic approach of Deaconu et al. (2001), we derive a stochastic particle approximation for the Smoluchowski coagulation equations. A convergence result for this model is obtained. Under quite stringent hypothesis we obtain a central limit theorem associated with our convergence. In spite of these restrictive technical assumptions, the rate of convergence result is interesting because it is the first obtained in this direction and seems to hold numerically under weaker hypothesis. This result answers a question closely connected to the Open Problem 16 formulated by Aldous (1999).     

À propos de l’indice de composition des nombres

 We define the index of composition λ(n) of an integer n ⩾ 2 as λ(n) = log n/log γ(n), where γ(n) stands for the product of the primes dividing n, and first establish that λ and 1/λ both have asymptotic mean value 1. We then establish that, given any ɛ > 0 and any integer k ⩾ 2, there exist infinitely many positive integers n such that . Considering the distribution function F(z,x) := #{n < x : λ(n) > z}, we prove that, given 1 < z < 2 and ɛ > 0, then, if x is sufficiently large,

Non unicité des solutions bornées pour un champ de vecteurs BV en dehors d'un hyperplan

We present here an example of a plane time-dependent bounded divergence-free vector field and a bounded non-zero solution of the homogeneous Cauchy problem for the associated transport equation. To cite this article: N. Depauw, C. R. Acad. Sci. Paris, Ser. I 337 (2003).     

ILEEMS: Methodology and Applications to Iron Oxides

ILEEMS is the acronym for Integral Low-energy Electron Mössbauer Spectroscopy. In this variant of Mössbauer spectroscopy the low-energy electrons, E < ～15 eV, emitted by the probe nuclei in the absorber are counted as a function of source velocity. As a consequence of their low energy, the detected electrons' origin lies within a very thin surface layer with thickness of a few nanometers and consequently, ILEEMS is a useful technique to examine surfaces of Fe-containing substances. In a first part of this paper the authors briefly describe the design of a home-made ILEEMS equipment allowing the temperature of the investigated sample to be varied between 77 K and room temperature. The second part of this contribution deals with a selection of results obtained from ILEEMS spectra for various Fe oxides. In particular, the following items are covered: (1) surface versus bulk Morin transition in small-particle and near-bulk hematite, α-Fe₂O₃; (2) bulk and thin-film magnetite, Fe₃O₄; (3) ferrihydrite, 5Fe₂O₃·9H₂0, goethite, α-FeOOH, and lepidocrocite, γ-FeOOH, all to some extent in relation to their morphology. Interesting and intriguing findings concerning the surface properties of these oxides were obtained and it is argued that the results encourage more systematic research in this and related fields using the surface-sensitive ILEEMS technique.     

In vivo magnetic resonance microscopy of Drosophilae at 9.4 T

In preclinical research, genetic studies have made considerable progress as a result of the development of transgenic animal models of human diseases. Consequently, there is now a need for higher resolution MRI to provide finer details for studies of small animals (rats, mice) or very small animals (insects). One way to address this issue is to work with high-magnetic-field spectrometers (dedicated to small animal imaging) with strong magnetic field gradients. It is also necessary to develop a complete methodology (transmit/receive coil, pulse sequence, fixing system, air supply, anesthesia capabilities, etc.). In this study, we developed noninvasive protocols, both in vitro and in vivo (from coil construction to image generation), for drosophila MRI at 9.4 T. The 10*10*80-μm resolution makes it possible to visualize whole drosophila (head, thorax, abdomen) and internal organs (ovaries, longitudinal and transverse muscles, bowel, proboscis, antennae and optical lobes). We also provide some results obtained with a Drosophila model of muscle degeneration. This opens the way for new applications of structural genetic modification studies using MRI of drosophila.     

Pump−probe experiments at the TEMPO beamline using the low‐α operation mode of Synchrotron SOLEIL

The SOLEIL synchrotron radiation source is regularly operated in special filling modes dedicated to pump–probe experiments. Among others, the low‐α mode operation is characterized by shorter pulse duration and represents the natural bridge between 50 ps synchrotron pulses and femtosecond experiments. Here, the capabilities in low‐α mode of the experimental set‐ups developed at the TEMPO beamline to perform pump–probe experiments with soft X‐rays based on photoelectron or photon detection are presented. A 282 kHz repetition‐rate femtosecond laser is synchronized with the synchrotron radiation time structure to induce fast electronic and/or magnetic excitations. Detection is performed using a two‐dimensional space resolution plus time resolution detector based on microchannel plates equipped with a delay line. Results of time‐resolved photoelectron spectroscopy, circular dichroism and magnetic scattering experiments are reported, and their respective advantages and limitations in the framework of high‐time‐resolution pump–probe experiments compared and discussed.