Prioritisation of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics.

There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against SARS-CoV-2. However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, EC90 values recalculated from in vitro anti-SARS-CoV-2 activity data was expressed as a ratio to the achievable maximum plasma concentrations (Cmax) at an approved dose in humans (Cmax/EC90 ratio). Only 14 of the 56 analysed drugs achieved a Cmax/EC90 ratio above 1. A more in-depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir-boosted) and sulfadoxine achieved plasma concentrations above their reported anti-SARS-CoV-2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (Kp Ulung ) was also simulated to derive a lung Cmax/EC50 as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir-boosted), tipranavir (ritonavir-boosted), ivermectin, azithromycin and lopinavir (ritonavir-boosted) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC50 . Nitazoxanide and sulfadoxine also exceeded their reported EC50 by 7.8- and 1.5-fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritising compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC90 values and discuss findings in the context of achievable exposures in humans, especially within target compartments such as the lung, in order to maximise the potential for success of proposed human clinical trials

Two distinct charge density waves in the quasione-dimensional metal Sr0.95NbO3.37 revealed by resonant soft X-ray scattering

The interplay of electron-electron and electron-lattice interactions plays an important role in determining exotic properties in strongly correlated electron systems. Of particular interest is quasi-one-dimensional SrNbOx metals, which are perovskite-related layered Carpy-Galy phases. Quasi-one-dimensional metals often exhibit a charge density wave (CDW) accompanied by lattice distortion; however, to date, the presence of a CDW in a quasi-one-dimensional metallic Carpy-Galy phase has not been detected. Here, we report the discovery of two distinct and simultaneous commensurate CDWs in Sr0.95NbO3.37 using resonant soft X-ray scattering (RSXS), namely, an electronic-(001) superlattice below similar to 200 K and an electronic-(002) Bragg peak. We also observe a non-electronic-(002) Bragg peak showing lattice distortion below similar to 150 K. Through the temperature dependence and resonance profile of these CDWs and the lattice distortion, as well as the relationship between the wavelength and charge density, these CDWs are determined to be Wigner crystals and Peierls-like instabilities, respectively. The electron-electron interaction is strong and dominant even up to 350 K, and upon cooling, it drives the electron-lattice interaction. The correlation length of the electronic-(001) superlattice is surprisingly larger than that of the electronic-(002) Bragg peak, and the superlattice is highly anisotropic. Supported by theoretical calculations, the CDWs are determined by the charge anisotropy and redistribution between the O-2p and Nb-4d orbitals, and the strength of the electronic-(001) superlattice is within the strong coupling limit.ISSN:1884-4057ISSN:1884-404

Photoinduced metastable dd-exciton-driven metal-insulator transitions in quasi-one-dimensional transition metal oxides

Photoinduced phase transitions in matters have gained tremendous attention over the past few years. However, their ultrashort lifetime makes their study and possible control very challenging. Here, we report on highly anisotropic d-d excitonic excitations yielding photoinduced metal-insulator transitions (MITs) in quasi-one-dimensional metals Sr1-yNbOx using Mueller-Matrix spectroscopic ellipsometry, transient ultraviolet Raman spectroscopy, transient mid-infrared reflectivity and angular-resolved photoemission spectroscopy supported with density functional theory. Interestingly, the MITs are driven by photo-pumping of d-d excitons, causing the metallic a-axis to become insulating while the insulating b- and c-axis concomitantly become a correlated metal. We assign these effects to an interplay between the melting of charge and lattice orderings along the different anisotropic optical axes and Bose-Einstein-like condensation of the photoinduced excitons. The long lifetime in the order of several seconds of the metastable MITs gives greater flexibility to study and manipulate the transient excitonic state for potential applications in exciton-based optoelectronic devices