Targeting two potential sites of SARS-CoV-2 main protease through computational drug repurposing.

Before the rise of SARS-CoV-2, emergence of different coronaviruses such as SARS-CoV and MERS-CoV has been reported that indicates possibility of the future novel pathogen from the coronavirus family at a pandemic level. In this context, explicit studies on identifying inhibitors focused on the coronavirus life cycle, are immensely important. The main protease is critical for the life cycle of coronaviruses. Majority of the work done on the inhibitor studies on the catalytically active dimeric SARS-CoV-2 main protease (Mpro), primarily focussed on the catalytic site of a single protomer, with a few targeting the dimeric site. In this study, we have exploited the FDA-approved drugs, for a computational drug repurposing study against the Mpro. A virtual screening approach was employed with docking and molecular dynamics (MD) methods. Out of 1576, FDA-approved compounds, our study suggests three compounds: netupitant, paliperidone and vilazodone as possible inhibitors with a potential to inhibit both sites (monomeric and dimeric) of the Mpro. These compounds were found to be stable during the MD simulations and their post simulation binding energies were also correlated for both the targeted sites, suggesting equal binding capacity. This unique efficiency of the reported compounds might support further experimental studies on developing inhibitors against SARS-CoV-2 main protease.Communicated by Ramaswamy H. Sarma.

Freeze-Thaw-Induced Physically Cross-linked Superabsorbent Polyvinyl Alcohol/Soy Protein Isolate Hydrogels for Skin Wound Dressing: In Vitro and In Vivo Characterization.

In this work, polyvinyl alcohol (PVA)- and soy protein isolate (SPI)-based scaffolds were prepared by physical cross-linking using the freeze-thaw method. The PVA/SPI ratio was varied to examine the individual effects of the two constituents. The physicochemical properties of the fabricated scaffolds were analyzed through Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, thermogravimetric analysis, and differential scanning calorimetry. The SPI concentration significantly affected the properties of scaffolds, such as the extent of gelation (%), pore size, porosity, degradation, swelling, and surface wettability. The in vitro degradation of fabricated hydrogels was evaluated in phosphate-buffered saline and lysozyme solution for a duration of 14 days. The in vitro compatibility of prepared hydrogels was evaluated by the MTT assay with NIH-3T3 cells (fibroblast). The water vapor transmission rate (WVTR) assays showed that all hydrogels possessed WVTR values in the range of 2000-2500 g m-2 day-1, which is generally recommended for ideal wound dressing. Overall, the obtained results reveal that the fabricated scaffolds have excellent biocompatibility, mechanical strength, porosity, stability, and degradation rate and thus carry enormous potential for tissue engineering applications. Furthermore, a full-thickness wound healing study performed in rats supported them as a promising wound dressing material.