Synthesis of Potential Antiviral Agents for SARS-CoV-2 Using Molecular Hybridization Approach.

We synthesized a set of small molecules using a molecular hybridization approach with good yields. The antiviral properties of the synthesized conjugates against the SAR-CoV-2 virus were investigated and their cytotoxicity was also determined. Among all the synthesized conjugates, compound 9f showed potential against SARS-CoV-2 and low cytotoxicity. The conjugates' selectivity indexes (SIs) were determined to correlate the antiviral properties and cytotoxicity. The observed biological data were further validated using computational studies.

Presentation and outcomes of acute appendicitis during COVID-19 pandemic: lessons learned from the Middle East-a multicentre prospective cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had a striking impact on healthcare services in the world. The present study aimed to investigate the impact of the COVID-19 pandemic on the presentation management and outcomes of acute appendicitis (AA) in different centers in the Middle East. METHODS: This multicenter cohort study compared the presentation and outcomes of patients with AA who presented during the COVID-19 pandemic in comparison to patients who presented before the onset of the pandemic. Demographic data, clinical presentation, management strategy, and outcomes were prospectively collected and compared. RESULTS: Seven hundred seventy-one patients presented with AA during the COVID pandemic versus 1174 in the pre-COVID period. Delayed and complex presentation of AA was significantly more observed during the pandemic period. Seventy-six percent of patients underwent CT scanning to confirm the diagnosis of AA during the pandemic period, compared to 62.7% in the pre-COVID period. Non-operative management (NOM) was more frequently employed in the pandemic period. Postoperative complications were higher amid the pandemic as compared to before its onset. Reoperation and readmission rates were significantly higher in the COVID period, whereas the negative appendicectomy rate was significantly lower in the pandemic period (p = 0.0001). CONCLUSION: During the COVID-19 pandemic, a remarkable decrease in the number of patients with AA was seen along with a higher incidence of complex AA, greater use of CT scanning, and more application of NOM. The rates of postoperative complications, reoperation, and readmission were significantly higher during the COVID period.

Molecular Docking and Dynamics Simulation Study of Hyrtios erectus Isolated Scalarane Sesterterpenes as Potential SARS-CoV-2 Dual Target Inhibitors.

Presently, the world is under the toll of pandemic coronavirus disease-2019 (COVID-19) outbreak caused by SARS-CoV-2. Lack of effective and safe therapeutics has stressed the scientific community for developing novel therapeutics capable of alleviating and stopping this pandemic. Within the presented study, molecular docking, ADME properties and all-atom molecular dynamic (MD) simulation, along with two standard antiviral agents (lopinavir and benzopurpurin-4B), were applied to investigate 15 scalaranes sesterterpenes natural compounds, purified from the Red Sea marine sponge Hyrtios erectus, as potential COVID-19 dual-target inhibitors. Following multi-step docking within COVID-19 main protease and Nsp15 endoribonuclease cavities, nine promising drug-like compounds exhibited higher docking scores as well as better interactions with the target's crucial residues than those of reference ligands. Compounds 2, 6, 11, and 15, were predicted to simultaneously subdue the activity of the two COVID-19 targets. Dynamics behavior of the best-docked molecules, compounds 15 and 6, within COVID-19 target pockets showed substantial stability of ligand-protein complexes as presented via several MD simulation parameters. Furthermore, calculated free-binding energies from MD simulation illustrated significant ligand's binding affinity towards respective target pockets. All provided findings supported the utility of scalarane-based sesterterpenes, particularly compounds 15 and 6, as promising lead candidates guiding the development of effective therapeutics against SARS-CoV-2.