Discovery,Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19

The COVID-19 pandemic needs no introduction at present. Only a few treatments are available for this disease, including remdesivir and favipiravir. Accordingly, the pharmaceutical industry is striving to develop new treatments for COVID-19. Molnupiravir, an orally active RdRp inhibitor, is in a phase 3 clinical trial against COVID-19. The objective of this review article is to enlighten the researchers working on COVID-19 about the discovery, recent developments, and patents related to molnupiravir. Molnupiravir was originally developed for the treatment of influenza at Emory University, USA. However, this drug has also demonstrated activity against a variety of viruses, including SARS-CoV-2. Now it is being jointly developed by Emory University, Ridgeback Biotherapeutics, and Merck to treat COVID-19. The published clinical data indicate a good safety profile, tolerability, and oral bioavailability of molnupiravir in humans. The patient-compliant oral dosage form of molnupiravir may hit the market in the first or second quarter of 2022. The patent data of molnupiravir revealed its granted compound patent and process-related patent applications. We also anticipate patent filing related to oral dosage forms, inhalers, and a combination of molnupiravir with marketed drugs like remdesivir, favipiravir, and baricitinib. The current pandemic demands a patient compliant, safe, tolerable, and orally effective COVID-19 treatment. The authors believe that molnupiravir meets these requirements and is a breakthrough COVID-19 treatment.     

A study of primary nucleation of calcium oxalate monohydrate: I‐Effect of supersaturation

There are various organic and inorganic constituents in kidney stones. Among them, calcium oxalate monohydrate (COM) is the primary inorganic constituent of kidney stones. However, the mechanisms of formation of kidney stones are not well understood. In this regard, a basic study is carried out for better understanding of nucleation, crystal growth and/or aggregation of formed COM crystals. The primary nucleation of calcium oxalate monohydrate is studied at the laboratory scale using turbidity measurements. Calcium chloride and potassium oxalate solutions are mixed and then added to a Turbidimeter tube for continuous recording of turbidity. Induction time (time to induce formation of detectable crystals) is estimated from time‐turbidity graphs. The effect of some urinary species, such as oxalate and calcium, on nucleation and crystallization characteristics of COM is determined by particle size distribution analysis, measuring weight of crystals and calculation of relative supersaturation. The classical nucleation theory is applied at high supersaturation ratios (SR) ranging from 1.6 to 2.2. The results indicate that nucleation rate increases with increasing supersaturation ratio from 0.81 × 10²⁸ nuclei/cm³.sec at 1.6 SR, to 18.02 × 10²⁸ nuclei/cm³.sec at 2.2 SR. On the other hand, free energy change and radius of critical nucleus are decreased as supersaturation ratio is increased. The nucleation rates are higher than those reported in literature. Such discrepancy is discussed on the bases of differences in experimental techniques. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

On the evolution of isotropic and kinematic hardening with finite plastic deformation Part I: compression/tension loading of OFHC copper cylinders

Compression tests followed by tension tests after re-machining were performed on annealed oxygen-free-high-conductivity copper cylinders. These tests were conducted at nine levels of maximum strain ranging from 5 to 50%. From this data, isotropic and kinematic hardening were calculated using 50, 1000 and 2000 microstrain offset definitions. Both isotropic and kinematic hardening were found to depend on the yield definition. Isotropic hardening, which increased with plastic strain with no signs of saturation, also increased with larger offset definition of yield. Kinematic hardening, which increased to 40% strain and appeared to saturate thereafter, decreased with higher offset definitions of yield.     

Falkner–Skan Flow with Stream-Wise Pressure Gradient and Transfer of Mass over a Dynamic Wall

In this work, an important model in fluid dynamics is analyzed by a new hybrid neurocomputing algorithm. We have considered the Falkner–Skan (FS) with the stream-wise pressure gradient transfer of mass over a dynamic wall. To analyze the boundary flow of the FS model, we have utilized the global search characteristic of a recently developed heuristic, the Sine Cosine Algorithm (SCA), and the local search characteristic of Sequential Quadratic Programming (SQP). Artificial neural network (ANN) architecture is utilized to construct a series solution of the mathematical model. We have called our technique the ANN-SCA-SQP algorithm. The dynamic of the FS system is observed by varying stream-wise pressure gradient mass transfer and dynamic wall. To validate the effectiveness of ANN-SCA-SQP algorithm, our solutions are compared with state-of-the-art reference solutions. We have repeated a hundred experiments to establish the robustness of our approach. Our experimental outcome validates the superiority of the ANN-SCA-SQP algorithm.     

Review of Building Integrated Photovoltaics System for Electric Vehicle Charging

The transition to sustainable transportation has fueled the need for innovative electric vehicle (EV) charging solutions. Building Integrated Photovoltaics (BIPV) systems have emerged as a promising technology that combines renewable energy generation with the infra-structure of buildings. This paper comprehensively reviews the BIPV system for EV charging, focusing on its technology, application, and performance. The review identifies the gaps in the existing literature, emphasizing the need for a thorough examination of BIPV systems in the context of EV charging. A detailed review of BIPV technology and its application in EV charging is presented, covering aspects such as the generation of solar cell technology, BIPV system installation, design options and influencing factors. Furthermore, the review examines the performance of BIPV systems for EV charging, focusing on energy, economic, and environmental parameters and their comparison with previous studies. Additionally, the paper explores current trends in energy management for BIPV and EV charging, highlighting the need for effective integration and recommending strategies to optimize energy utilization. Combining BIPV with EV charging provides a promising approach to power EV chargers, enhances building energy efficiency, optimizes the building space, reduces energy losses, and decreases grid dependence. Utilizing BIPV-generated electricity for EV charging provides electricity and fuel savings, offers financial incentives, and increases the market value of the building infrastructure. It significantly lowers greenhouse gas emissions associated with grid and vehicle emissions. It creates a closed-loop circular economic system where energy is produced, consumed, and stored within the building. The paper underscores the importance of effective integration between Building Integrated Photovoltaics (BIPV) and Electric Vehicle (EV) charging, emphasizing the necessity of innovative grid technologies, energy storage solutions, and demand-response energy management strategies to overcome diverse challenges. Overall, the study contributes to the knowledge of BIPV systems for EV charging by presenting practical energy management, effectiveness and sustainability implications. It serves as a valuable resource for researchers, practitioners, and policymakers working towards sustainable transportation and energy systems.     

Cleavage Mechanoluminescence in Crystals

When a crystal is cleaved, initially the mechanoluminescence (ML) intensity increases linearly with time, attains an optimum-value I_m at a particular value of timet_m, and then decays exponentially with time. Cleavage ML provides a new tool to determine the velocity, v of cracks in crystals, and it may be given by v = H/t_m, where H is the thickness of the crystal. Both, the peak ML intensity I_m and total ML intensity I_T increase linearly with the area of newly created surfaces A as well as with the surface charge density γ. The ML intensity decreases with temperature primarily due to the decrease in the surface charge density. Beyond a particular temperature, the surface charge density may decrease to such a value where the breakdown of gases and solids may not be possible and thereby the ML may not appear. Depending on the prevailing conditions either the ML emission resembling gas discharge or other types of the luminescence of solids, or that having these two characters may be obtained. There exists a good correlation between the theoretical and experimental results obtained for cleavage ML in crystals.     

Kinetics of the interaction of Cd(II)-histidine complex with ninhydrin in absence and presence of cationic and anionic micelles

Kinetics of the interaction of Cd(II)-histidine complex with ninhydrin has been carried out at pH 5.02 (acetic acid-sodium acetate buffer) under varying conditions of reactant concentrations, temperature, and surfactant concentrations. The order of the reaction with respect to Cd(II)-histidine complex was unity while it was fractional with respect to ninhydrin. On the basis of these studies a mechanism has been proposed. In the absence of the surfactants, the reaction followed rate equation: while, in presence of surfactants, the following rate equation was obeyed: Anionic micelles of sodium dodecyl sulphate catalyze the reaction with the rate reaching a maximum at ca. 0.10 mol dm⁻³ surfactant. The surfactant decreases activation enthalpy and makes it more negative. Cationic micelles of cetyltrimethylammonium bromide strongly inhibit the reaction and increase the activation enthalpy but make the activation entropy more positive than the SDS micelles. Added salts (KNO₃ and NaCl) inhibit the catalysis, and the effect is more with the latter. The rate constants, binding constants with surfactants, and the index of cooperativity have been evaluated. © 1997 John Wiley & Sons, Inc.