Correction to "Targeting the Spike: Repurposing Mithramycin and Dihydroergotamine to Block SARS-CoV-2 Infection".

[This corrects the article DOI: 10.1021/acsomega.3c02921.].

Targeting the Spike: Repurposing Mithramycin and Dihydroergotamine to Block SARS-CoV-2 Infection.

The urgency to find complementary therapies to current SARS-CoV-2 vaccines, whose effectiveness is preserved over time and not compromised by the emergence of new and emerging variants, has become a critical health challenge. We investigate the possibility of jamming the opening of the Receptor Binding Domain (RBD) of the spike protein of SARS-CoV-2 with small compounds. Through in silico screening, we identified two potential candidates that would lock the Receptor Binding Domain (RBD) in a closed configuration, preventing the virus from infecting the host cells. We show that two drugs already approved by the FDA, mithramycin and dihydroergotamine, can block infection using concentrations in the µM range in cell-based assays. Further STD-NMR experiments support dihydroergotamine's direct interaction with the spike protein. Overall, our results indicate that repurposing of these compounds might lead to potential clinical drug candidates for the treatment of SARS-CoV-2 infection.

On the role of polydispersity on the phase diagram of colloidal rods.

The rich and complex phase diagram typical of anisotropic biological or synthetic nanoparticles, has brought a great deal of interest over the equilibrium phase behaviour of non-spherical colloids. Amongst the class of anisotropic nanoparticles, hard spherocylindrical colloids have been, over the years, extensively studied because of their optical properties, for their rich phase diagrams, and their important industrial applications, as model particles for biological systems (viruses), or for example as potential drug carriers having the ability of surviving the attacks of the immune systems. As real anisotropic nanoparticles are often polydisperse in size and/or in shape, unveiling the effect of such a perturbation over their equilibrium phase diagram is of paramount importance. This work focuses on the effects of polydispersity over the full equilibrium phase diagram of hard spherocylindrical colloids (HSCs). Previous studies showed that a polydispersity in L alters the equilibrium phase diagram of HSCs. With this work we determine, both theoretically as well as computationally, the effects due to a generic polydispersity, namely in D, in L and, in both ones, on the equilibrium phase diagram and introduce a viable theoretical generalisation of the Onsager theory that allows us to get some insight into the observed phase behaviour.

Unveiling adsorption generality in polymeric macromolecules.

Unveiling a general law for adsorption within macromolecules sets an important step forward in the design of nanomaterials with tunable and controllable properties. Reaching such a generalised control would have an important outcome in a plethora of possible fields, from biomedical applications up to materials science. In fact, the definition of classes regrouping adsorbing macromolecules with different geometrical or chemical properties would enormously simplify the design of controllable adsorbing materials, especially when geometrical or chemical constraints are set by the particular application. In this work we derive, through a combination of Scaling Theories and Molecular Dynamics Simulations, a general law for adsorption of spherical non-deformable colloidal nanoparticles within polymeric macromolecules of different geometries. Starting from the case of adsorption of a single colloid within macromolecular systems, we extend the results to the case in which finite adsorption takes place. We then derive simple predictions linking the adsorption potential to general properties of classes of macromolecules, and introduce a set of measurable quantities that can be exploited as an indirect measurement for loading.

Edinburgh Lamarckians? The Authorship of Three Anonymous Papers (1826-1829).

In the space of four years, from 1826 to 1829, the Edinburgh New Philosophical Journal published three anonymous articles seemingly advocating doctrines inspired by Jean-Baptiste Lamarck. Decades of scholarship have initially attributed the most outspoken of the three articles, the 1826 "Observations on the Nature and Importance of Geology," to Robert Grant, and subsequently to Robert Jameson, thanks to a critical reassessment by James Secord (1991). More recently, scholars have also ascribed to Jameson an article published in 1829, "Of the Continuity of the Animal Kingdom by Means of Generation from the First Ages of the World to the Present Times." A third short contribution, the 1827 "Of the Changes which Life has Experienced on the Globe" has been credited to the Franco-German Ami Boué. Research undertaken over several years has led to the identification of the three authors hiding behind the veil of anonymity. They were not the ones scholars have agreed upon, nor were they really "Lamarckians." The discussion of the ways in which the three texts reached Edinburgh broadens our understanding of the daily working practices of contemporary periodicals and of the networks of circulation of texts at the Continental level. Finally, when considered within their proper conceptual and social context, the three articles throw light on the many ways in which, during the 1820s, European amateurs, naturalists, and journalists debated the succession of life forms throughout the history of the Earth.

Coarse graining and adsorption in bottlebrush-colloid mixtures.

We study the adsorption properties in bottlebrush/colloid binary mixtures by combining scaling theories, theoretical predictions, self-consistent field computations (SCFC), and molecular dynamics simulations. In particular, we focus on adsorption in the case in which an attraction is set between the two species, by analysing the solution properties for a range of interactions and the size ratio between colloids and bottlebrushes, in the case in which colloids are smaller than the macromolecules. We show that the onset of adsorption is dominated by the local properties of the adsorbing guest particle. This allows us to use the local similarity between a cylindrical bottlebrush and a spherical star polymer to predict the region of the parameter space in which the adsorption takes place. By employing simple scaling arguments, we thus extend the analytical results on the adsorption obtained for binary mixtures of star polymers/colloid nanoparticles. We then validate our predictions with molecular dynamics simulations. Moreover, by means of SCFC, we assess the adsorption-to-depletion transition of nanoparticles in polymeric bottlebrushes. Our results pave the road towards a smart rational design and coarse-graining of adsorbing/releasing systems, where an elongated shape might play an important role.

Theoretical and Experimental Design of Heavy Metal-Mopping Magnetic Nanoparticles.

Herein, we show a comprehensive experimental, theoretical, and computational study aimed at designing macromolecules able to adsorb a cargo at the nanoscale. Specifically, we focus on the adsorption properties of star diblock copolymers, i.e., macromolecules made by a number f of H-T diblock copolymer arms tethered on a central core; the H monomeric heads, which are closer to the tethering point, are attractive toward a specific target, while the T monomeric tails are neutral to the cargo. Experimentally, we exploited the adaptability of poly(2-oxazoline)s (POxs) to realize block copolymer-coated nanoparticles with a proper functionalization able to interact with heavy metals and show or exhibit a thermoresponsive behavior in aqueous solution. We here present the synthesis and analysis of the properties of a high molecular mass block copolymer featured by (i) a polar side chain, capable of exploiting electrostatic and hydrophilic interaction with a predetermined cargo, and (ii) a thermoresponsive scaffold, able to change the interaction with the media by tuning the temperature. Afterward, the obtained polymers were grafted onto iron oxide nanoparticles and the thermoresponsive properties were investigated. Through isothermal titration calorimetry, we then analyzed the adsorption properties of the synthesized superparamagnetic nanoparticles for heavy metal ions in aqueous solution. Additionally, we use a combination of scaling theories and simulations to link equilibrium properties of the system to a prediction of the loading properties as a function of size ratio and effective interactions between the considered species. The comparison between experimental results on adsorption and theoretical prediction validates the whole design process.

Simulated Epidemics in 3D Protein Structures to Detect Functional Properties.

The outcome of an epidemic is closely related to the network of interactions between individuals. Likewise, protein functions depend on the 3D arrangement of their residues and the underlying energetic interaction network. Borrowing ideas from the theoretical framework that has been developed to address the spreading of real diseases, we study for the first time the diffusion of a fictitious epidemic inside the protein nonbonded interaction network, aiming to study network features and properties. Our approach allows us to probe the overall stability and the capability of propagating information in complex 3D structures, proving to be very efficient in addressing different problems, from the assessment of thermal stability to the identification of functional sites.

Exploiting scaling laws for designing polymeric bottle brushes: a theoretical coarse-graining for homopolymeric branched polymers.

Bottle brushes are polymeric macromolecules made of a linear polymeric backbone grafted with side chains. The choice of the grafting density σg, the length ns the grafted side chains and their chemical nature fully determines the properties of each macromolecule, such as its elasticity and its folding behaviour. Typically, experimental bottle brushes are systems made of tens of thousands of monomeric units, rendering a computational approach extremely expensive, especially in the case of bottle brush solutions. A proper coarse graining description of these macromolecules thus appears essential. We present here a theoretical approach able to develop a general, transferable and analytical multi-scale coarse graining of homopolymeric bottle brush polymers under good solvent conditions. Starting from scaling theories, each macromolecule is mapped onto a chain of tethered star polymers, whose effective potential is known from scaling predictions, computational and experimental validations and can be expressed as a function of the number of arms f, and the length na of each arm. Stars are then tethered to one another and the effective potential between them is shown to only depend on the key parameters of the original bottle brush polymer (σg, ns). The generalised form of the effective potential is then used to reproduce properties of the macromolecules obtained both with scaling theories and with simulations. The general form of the effective potentials derived in the current study allows a theoretical and computational description of the properties of homopolymeric bottle brush polymers for all grafting densities and all lengths of both backbone and grafted arms, opening the path for a manifold of applications.

Insights on protein thermal stability: a graph representation of molecular interactions.

MOTIVATION: Understanding the molecular mechanisms of thermal stability is a challenge in protein biology. Indeed, knowing the temperature at which proteins are stable has important theoretical implications, which are intimately linked with properties of the native fold, and a wide range of potential applications from drug design to the optimization of enzyme activity. RESULTS: Here, we present a novel graph-theoretical framework to assess thermal stability based on the structure without any a priori information. In this approach we describe proteins as energy-weighted graphs and compare them using ensembles of interaction networks. Investigating the position of specific interactions within the 3D native structure, we developed a parameter-free network descriptor that permits to distinguish thermostable and mesostable proteins with an accuracy of 76% and area under the receiver operating characteristic curve of 78%. AVAILABILITY AND IMPLEMENTATION: Code is available upon request to edoardo.milanetti@uniroma1.it. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

What do you mean by a periodical? Forms and functions

The word 'periodical' immediately calls to mind huge stacks of bound volumes neatly arranged on library shelves. Yet, in historical terms, it would be hard to claim that 'periodical' is a word endowed with a definite and univocal connotation. Even the criterion of 'periodicity' leaves a lot out of account. Forms historically assumed by periodicals often envisaged regular schedules of appearance, but this was often more of a wish than a reality. Thus, great care needs to be taken in accepting at face value the dating of issues and volumes. Scientific periodicals, whether purely professional or purely commercial (and the many forms in between), existed in given historical circumstances and had to compete with different and alternative forms of publication which were also issued in instalments (especially dictionaries and encyclopaedias). They were not the only or even the preferred vehicle for a scientist to communicate or engage in debate. The role of the reading public, in science as well as in many other matters, was never one of a passive receiver: during the long nineteenth century, in several countries, readers claimed the right to intervene in scientific debates, and favoured publications that appeared to accommodate their demands.

Before darwin: transformist concepts in European natural history.

Lack of consideration of the complex European scientific scene from the late 18th century to the mid-decades of the 19th century has produced partial and often biased reconstructions of priorities, worries, implicit and explicit philosophical and at times political agendas characterizing the early debates on species. It is the purpose of this paper firstly to critically assess some significant attempts at broadening the historiographic horizon concerning the immediate context to Darwin's intellectual enterprise, and to devote the second part to arguing that a multi-faceted European debate on the transformation of life forms had already occurred in Europe around 1800. Of this debate, contrary to long cherished views, Lamarck's was only one voice, amongst many. Naturalists active in different national contexts elaborated solutions and proposed doctrines that shared several viewpoints, yet clearly stemmed from a variety of disciplinary traditions and problematic contexts.

[Lamarck's teaching on invertebrates at Paris's National Museum of Natural History between 1795-1823]. / Des pharmaciens assistent au cours des animaux sans vertébres professé par Lamarck au Paris Muséum national d'histoire naturelle entre (1795-1823).

Lamarck's teaching attracted nearly a thousand students. At least forty of them were (or became) pharmacists. Many practised in chemist's or military dispensaries. Some were known as scientists, either chemists (Braconnot, Duspasquier, Macaire), botanists (Bonnemaison, Nestler, Robert) or naturalists and travellers (Aucher-Elroy, Fontanier). Further research is necessary to elucidate the role of these pharmacists in the diffusion of scientific ideas, chiefly the transformists ones, during the nineteenth century.