Time dependent viscoelastic rheological response of pure, modified and synthetic bituminous binders

Bitumen is a viscoelastic material that exhibits both elastic and viscous components of response and displays both a temperature and time dependent relationship between applied stresses and resultant strains. In addition, as bitumen is responsible for the viscoelastic behaviour of all bituminous materials, it plays a dominant role in defining many of the aspects of asphalt road performance, such as strength and stiffness, permanent deformation and cracking. Although conventional bituminous materials perform satisfactorily in most highway pavement applications, there are situations that require the modification of the binder to enhance the properties of existing asphalt material. The best known form of modification is by means of polymer modification, traditionally used to improve the temperature and time susceptibility of bitumen. Tyre rubber modification is another form using recycled crumb tyre rubber to alter the properties of conventional bitumen. In addition, alternative binders (synthetic polymeric binders as well as renewable, environmental-friendly bio-binders) have entered the bitumen market over the last few years due to concerns over the continued availability of bitumen from current crudes and refinery processes. This paper provides a detailed rheological assessment, under both temperature and time regimes, of a range of conventional, modified and alternative binders in terms of the materials dynamic (oscillatory) viscoelastic response. The rheological results show the improved viscoelastic properties of polymer- and rubber-modified binders in terms of increased complex shear modulus and elastic response, particularly at high temperatures and low frequencies. The synthetic binders were found to demonstrate complex rheological behaviour relative to that seen for conventional bituminous binders

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID

Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property–free knowledge base for future anticoronavirus drug discovery