SARS-CoV-2 Inhibition by Sulfonated Compounds.

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) depends on angiotensin converting enzyme 2 (ACE2) for cellular entry, but it might also rely on attachment receptors such as heparan sulfates. Several groups have recently demonstrated an affinity of the SARS-CoV2 spike protein for heparan sulfates and a reduced binding to cells in the presence of heparin or heparinase treatment. Here, we investigated the inhibitory activity of several sulfated and sulfonated molecules, which prevent interaction with heparan sulfates, against vesicular stomatitis virus (VSV)-pseudotyped-SARS-CoV-2 and the authentic SARS-CoV-2. Sulfonated cyclodextrins and nanoparticles that have recently shown broad-spectrum non-toxic virucidal activity against many heparan sulfates binding viruses showed inhibitory activity in the micromolar and nanomolar ranges, respectively. In stark contrast with the mechanisms that these compounds present for these other viruses, the inhibition against SARS-CoV-2 was found to be simply reversible

Testing the foundation of quantum physics in space via Interferometric and non-interferometric experiments\ua0with mesoscopic nanoparticles

This perspective presents current and future possibilities offered by space technology for testing quantum mechanics, with a focus on mesoscopic superposition of nanoparticles and the potential of interferometric and non-interferometric experiments in space.Quantum technologies are opening novel avenues for applied and fundamental science at an impressive pace. In this perspective article, we focus on the promises coming from the combination of quantum technologies and space science to test the very foundations of quantum physics and, possibly, new physics. In particular, we survey the field of mesoscopic superpositions of nanoparticles and the potential of interferometric and non-interferometric experiments in space for the investigation of the superposition principle of quantum mechanics and the quantum-to-classical transition. We delve into the possibilities offered by the state-of-the-art of nanoparticle physics projected in the space environment and discuss the numerous challenges, and the corresponding potential advancements, that the space environment presents. In doing this, we also offer an ab-initio estimate of the potential of space-based interferometry with some of the largest systems ever considered and show that there is room for tests of quantum mechanics at an unprecedented level of detail

Advances in the development of entry inhibitors for sialic-acid-targeting viruses

Over the past decades, several antiviral drugs have been developed to treat a range of infections. Yet the number of treatable viral infections is still limited, and resistance to current drug regimens is an ever-growing problem. Therefore, additional strategies are needed to provide a rapid cure for infected individuals. An interesting target for antiviral drugs is the process of viral attachment and entry into the cell. Although most viruses use distinct host receptors for attachment to the target cell, some viruses share receptors, of which sialic acids are a common example. This review aims to give an update on entry inhibitors for a range of sialic-acidtargeting viruses and provides insight into the prospects for those with broad-spectrum potential

Monitoring of a controlled space flexible multibody by means of embedded piezoelectric sensors and cameras synergy

Interaction between elastic dynamics and attitude control is a serious problem in space operations, which often involve satellites with highly flexible appendages. Monitoring and eventually control of the vibrations are a major concern to avoid a decrease in the expected performance. In particular, the classic case of a central bus with two lateral appendages (solar panels) is considered. The design of a system for structural vibration monitoring is proposed both from a numerical and an experimental point of view. Piezoelectric devices are a usual solution for measuring the deformation of the structures. In the proposed work, optical sensors are also implemented: the combined use of the two sets allows for the monitoring of the elastic displacement of the solar panels and for the reconstruction of the modal shapes of the entire flexible multibody syste

Attitude stabilization of a flexible spacecraft using combined PZT/optical sensors

The problem of stabilizing the time delayed control of a flexible space structure is analyzed in this paper. A free floating platform is used to investigate the space multibody dynamics and control. A first necessary step to develop stabilizing techniques is considered the availability of a set of measurements as complete as possible: in particular measurements of the elastic vibrations are necessary in addition to classic attitude measurements. At the scope, a net of PZT sensors have been designed and manufactured on a composite material panel, purposely built to resemble a space structure. A combined use of the PZT/optical sensor is proposed, where the role of the camera is to estimate the PZT parameters that can be changed after the manufacturing or for environmental aging. When this calibration process is performed, PZT can be used as standalone sensors for measuring also the elastic displacement of the structure. Once these measurements of attitude and elastic displacement are obtained, two stabilizing techniques have been developed, the Finite Spectrum Analysis, already known in literature, and the newly developed High Fidelity Filter approach, based on the design of a Kalman filter with large confidence on the process dynamics. It is shown that both techniques manages to increase the delay margin of the system, thus obtaining a stable maneuver, but the second approach reach this goal with very low residual vibrations and a remarkable fuel saving

Effects of a High Fidelity Filter on the attitude stabilization of a flexible spacecraft

The problem of stabilizing the time delayed control of a flexible space structure is analyzed in this paper. A free floating platform is used to investigate the space multibody dynamics and control. A first necessary step to develop stabilizing techniques is considered the availability of a set of measurements as complete as possible: in particular measurements of the elastic vibrations are necessary in addition to classic attitude measurements. At the scope, a net of PZT sensors have been designed and manufactured on a composite material panel, purposely built to resemble a space structure. A combined use of the PZT/optical sensor is proposed, where the role of the camera is to estimate the PZT parameters that can be changed after the manufacturing or for environmental aging. When this calibration process is performed, PZT can be used as standalone sensors for measuring also the elastic displacement of the structure. Once these measurements of attitude and elastic displacement are obtained, two stabilizing techniques have been developed, the Finite Spectrum Analysis, already known in literature, and the newly developed High Fidelity Filter approach, based on the design of a Kalman filter with large confidence on the process dynamics. It is shown that both techniques manage to increase the delay margin of the system, thus obtaining a stable maneuver, but the second approach reach this goal with very low residual vibrations and a remarkable fuel saving

Sulfonated Nanomaterials with Broad-Spectrum Antiviral Activity Extending beyond Heparan Sulfate-Dependent Viruses

Viral infections are among the main causes of death worldwide, and we lack antivirals for the majority of viruses. Heparin-like sulfated or sulfonated compounds have been known for decades for their ability to prevent infection by heparan sulfate proteoglycan (HSPG)-dependent viruses but only in a reversible way. We have previously shown that gold nanoparticles and beta-cyclodextrins coated with mercapto-undecane sulfonic acid (MUS) inhibit HSPG-dependent viruses irreversibly while retaining the low-toxicity profile of most heparin-like compounds. In this work, we show that, in stark contrast to heparin, these compounds also inhibit different strains of influenza virus and vesicular stomatitis virus (VSV), which do not bind HSPG. The antiviral action is virucidal and irreversible for influenza A virus (H1N1), while for VSV, there is a reversible inhibition of viral attachment to the cell. These results further broaden the spectrum of activity of MUS-coated gold nanoparticles and beta-cyclodextrins

Polyanionic amphiphilic dendritic polyglycerols as broad-spectrum viral inhibitors with a virucidal mechanism

Heparin has been known to be a broad-spectrum inhibitor of viral infection for almost 70 years, and it has been used as a medication for almost 90 years due to its anticoagulant effect. This nontoxic biocompatible polymer efficiently binds to many types of viruses and prevents their attachment to cell membranes. However, the anticoagulant properties are limiting their use as an antiviral drug. Many heparin-like compounds have been developed throughout the years; however, the reversible nature of the virus inhibition mechanism has prevented their translation to the clinics.In vivo, such a mechanism requires the unrealistic maintenance of the concentration above the binding constant. Recently, we have shown that the addition of long hydrophobic linkers to heparin-like compounds renders the interaction irreversible while maintaining the low-toxicity and broad-spectrum activity. To date, such hydrophobic linkers have been used to create heparin-like gold nanoparticles and β-cyclodextrins. The former achieves a nanomolar inhibition concentration on a non-biodegradable scaffold. The latter, on a fully biodegradable scaffold, shows only a micromolar inhibition concentration. Here, we report that the addition of hydrophobic linkers to a new type of multifunctional scaffold (dendritic polyglycerol, dPG) creates biocompatible compounds endowed with nanomolar activity. Furthermore, we present an in-depth analysis of the molecular design rules needed to achieve irreversible virus inhibition. The most active compound (dPG-5) showed nanomolar activity against herpes simplex virus 2 (HSV-2) and respiratory syncytial virus (RSV), giving a proof-of-principle for broad-spectrum while keeping low-toxicity. In addition, we demonstrate that the virucidal activity leads to the release of viral DNA upon the interaction between the virus and our polyanionic dendritic polymers. We believe that this paper will be a stepping stone toward the design of a new class of irreversible nontoxic broad-spectrum antivirals

Test quantum mechanics in space — invest US$1 billion

Shooting glass beads across the inside of a satellite could probe the limits of quantum wave behaviour. Here\u2019s how