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After over two years of living with Covid-19 and hundreds of million cases worldwide there is still an unmet need to find proper treatments for the novel coronavirus, due also to the rapid mutation of its genome. In this context, a drug repositioning study has been performed, using in silico tools targeting Delta Spike protein/ACE2 interface. To this aim, it has been virtually screened a library composed by 4388 approved drugs through a deep learning-based QSAR model to identify protein-protein interactions modulators for molecular docking against Spike receptor binding domain (RBD). Binding energies of predicted complexes were calculated by Molecular Mechanics/Generalized Born Surface Area from docking and molecular dynamics simulations. Four out of the top twenty ranking compounds showed stable binding modes on Delta Spike RBD and were evaluated also for their effectiveness against Omicron. Among them an antihistaminic drug, fexofenadine, revealed very low binding energy, stable complex, and interesting interactions with Delta Spike RBD. Several antihistaminic drugs were found to exhibit direct antiviral activity against SARS-CoV-2 in vitro, and their mechanisms of action is still debated. This study not only highlights the potential of our computational methodology for a rapid screening of variant-specific drugs, but also represents a further tool for investigating properties and mechanisms of selected drugs., (© 2023. The Author(s).)

SARS-CoV-2 infection shows a wide-ranging clinical severity, requiring prognostic markers. We focused on S100B, a calcium-binding protein present in biological fluids, being a reliable biomarker in disorders having inflammatory processes as common basis and RAGE as main receptor. Since Covid-19 is characterized by a potent inflammatory response also involving RAGE, we tested if S100B serum levels were related to disease severity. Serum samples (n = 74) were collected from hospitalized SARS-CoV-2 positive patients admitted to Covid center. Illness severity was established by admission clinical criteria and Covid risk score. Treatment protocols followed WHO guidelines available at the time. Circulating S100B was determined by ELISA assay. Statistical analysis used Pearson's χ 2 test, t-Test, and ANOVA, ANCOVA, Linear Regression. S100B was detected in serum from Covid-19 patients, significantly correlating with disease severity as shown both by the level of intensity of care (p < 0.006) as well by the value of Covid score (Multiple R-squared: 0.3751); the correlation between Covid-Score and S100B was 0.61 (p < 0.01). S100B concentration was associated with inflammation markers (Ferritin, C-Reactive Protein, Procalcitonin), and organ damage markers (Alanine Aminotransferase, Creatinine). Serum S100B plays a role in Covid-19 and can represent a marker of clinical severity in Sars-CoV-2 infected patients.