Targeting SARS-CoV-2 RBD Interface: a Supervised Computational Data-Driven Approach to Identify Potential Modulators

Coronavirus disease 2019 (COVID-19) has spread out as a pandemic threat affecting over 2 million people. The infectious process initiates via binding of SARS-CoV-2 Spike (S) glycoprotein to host angiotensin-converting enzyme 2 (ACE2). The interaction is mediated by the receptor-binding domain (RBD) of S glycoprotein, promoting host receptor recognition and binding to ACE2 peptidase domain (PD), thus representing a promising target for therapeutic intervention. Herein, we present a computational study aimed at identifying small molecules potentially able to target RBD. Although targeting PPI remains a challenge in drug discovery, our investigation highlights that interaction between SARS-CoV-2 RBD and ACE2 PD might be prone to small molecule modulation, due to the hydrophilic nature of the bi-molecular recognition process and the presence of druggable hot spots. The fundamental objective is to identify, and provide to the international scientific community, hit molecules potentially suitable to enter the drug discovery process, preclinical validation and development.     

Pectin: A Long-Neglected Broad-Spectrum Antibacterial

First reported in the late 1930s and partly explained in 1970, the antibacterial activity of pectin remained almost ignored until the late 1990s. The concomitant emergence of research on natural antibacterials and new usages of pectin polysaccharides, including those in medicine widely researched in Russia, has led to a renaissance of research into the physiological properties of this uniquely versatile polysaccharide ubiquitous in plants and fruits. By collecting scattered information, this study provides an updated overview of the subtle factors affecting the behaviour of pectin as an antimicrobial. Less-degraded pectin extracted by acid-free routes, we argue in the conclusions, will soon find applications from new treatments for polymicrobial infections to use as an implantable biomaterial in tissue and bone engineering.     

Role of Extracellular Vesicles in Epithelial Ovarian Cancer: A Systematic Review

Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial–mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients.     

Synthesis,Molecular Modeling and Biological Evaluation of Metabolically Stable Analogues of the Endogenous Fatty Acid Amide Palmitoylethanolamide

Palmitoylethanolamide (PEA) belongs to the class of N-acylethanolamine and is an endogenous lipid potentially useful in a wide range of therapeutic areas; products containing PEA are licensed for use in humans as a nutraceutical, a food supplement, or food for medical purposes for its analgesic and anti-inflammatory properties demonstrating efficacy and tolerability. However, the exogenously administered PEA is rapidly inactivated; in this process, fatty acid amide hydrolase (FAAH) plays a key role both in hepatic metabolism and in intracellular degradation. So, the aim of the present study was the design and synthesis of PEA analogues that are more resistant to FAAH-mediated hydrolysis. A small library of PEA analogues was designed and tested by molecular docking and density functional theory calculations to find the more stable analogue. The computational investigation identified RePEA as the best candidate in terms of both synthetic accessibility and metabolic stability to FAAH-mediated hydrolysis. The selected compound was synthesized and assayed ex vivo to monitor FAAH-mediated hydrolysis and to confirm its anti-inflammatory properties. ¹H-NMR spectroscopy performed on membrane samples containing FAAH in integral membrane protein demonstrated that RePEA is not processed by FAAH, in contrast with PEA. Moreover, RePEA retains PEA’s ability to inhibit LPS-induced cytokine release in both murine N9 microglial cells and human PMA-THP-1 cells.     

Ultrathin hydroxyapatite coating on pure magnesium substrate prepared by pulsed electron ablation technique

Magnesium (Mg) as a potential material for biodegradable implants is attractive due to its mechanical similarity to the bone tissue and nontoxic corrosion products. However, the rapid corrosion rate of bare magnesium is associated with hydrogen release, which may complicate the healing process. The corrosion rate may be reduced by suitable alloying, but concurrently the biocompatibility of such alloy might be deteriorated. Another way of reduction of the corrosion rate is coating. Hydroxyapatite (HA)-based coating is considered to improve biocompatibility as well as decrease the corrosion rate by the barrier effect. In this study, ultrathin (150 nm) HA and HA containing Sr coatings are deposited via pulsed electron ablation technique on pure Mg. The microstructure of the coating was assessed by scanning electron microscopy. Electrochemical methods were used to investigate the corrosion properties of prepared coatings. The materials covered by this layer were characterized by superior corrosion behavior, with corrosion rates of coated samples up to five times lower as compared with the uncoated ones. Such coating is the thinnest coating found in the literature sources.     

SKPFM investigations of intermetallic compounds of innovative Er‐ and Zr‐containing Al–Si–Mg alloys and their influence on corrosion localization in saline solution

The paper aims at characterizing the influence of intermetallic compounds on the corrosion localization of innovative Al–Si–Mg Er‐ and Zr‐containing casting alloys. Samples of the investigated materials were studied by means of optical and scanning electron microscope micrographs, immersion tests, and scanning Kelvin probe force microscope (SKPFM) analyses in the T6 temper. Combination of immersion tests and SKPFM analyses allowed to identify those classes of intermetallic compounds promoting localization of the corrosion process. It was found that intermetallic compounds richer in Fe were the most critical for corrosion localization; furthermore, additions of Er caused a marked decrease of the potential difference of intermetallic compounds with respect to the Al matrix and a consequent less intense microgalvanic coupling, which translates into slower corrosion kinetics. Further, Zr additions slightly increased the potential difference of intermetallic compounds with the Al matrix, promoting a faster corrosion process.     

Emerging specializations,competences and firms' proximity in digital industries: The case of London

In order to overcome the limitations of defining industrial specializations in digital industries through SIC codes, this paper suggests measuring the specializations and competences of these industries on the basis of the degree of digital technologies present in the products and services supplied. Metadata from CrunchBase are employed, as proxies of firms' specializations and competences which are defined as the fields of activity in which firms are involved. Applying a network analysis, these specializations and competences are linked to the recognition of emerging digital technologies and the strongest combinations of products and services. We tested the proposed methodology on London, a leading centre for the digital economy.     

A ticket to ride: Education and migration from lagging areas

National policies may have heterogeneous effects at the regional level. When coming to programmes aimed at increasing human capital, worker mobility from poorer to richer regions can reduce the benefits of the policy for the former areas. We focus on Italy and estimate the impact of education on the probability of migrating from a lagging area to a leading one. Endogeneity is addressed by exploiting an increase in the minimum school-leaving age in an instrumental variable framework. We find that one additional year of education increases the probability to migrate by 1.7 percentage points (9% of the average migration rate).