Anti-ACE monoclonal antibody, clone 3F3

The membrane-anchored spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a pivotal role in directing the fusion of the virus particle mediated by the host cell receptor angiotensin-converting enzyme 2 (ACE-2). The fusion peptide region of the S protein S2 domain provides SARSCoV-2 with the biological machinery needed for direct fusion to the host lipid membrane. In our present study, computer-aided drug design strategies were used for the identification of FDA-approved small molecules using the optimal structure of the S2 domain, which exhibits optimal interaction ratios, structural features, and energy variables, which were evaluated based on their performances in molecular docking, molecular dynamics simulations, molecular mechanics/generalized Born model and solvent accessibility binding free energy calculations of molecular dynamics trajectories, and statistical inferences. Among the 2,625 FDA-approved small molecules, chloramphenicol succinate, imipenem, and imidurea turned out to be the molecules that bound the best at the fusion peptide hydrophobic pocket. The principal interactions of the selected molecules suggest that the potential binding site at the fusion peptide region is centralized amid the Lys790, Thr791, Lys795, Asp808, and Gln872 residues. IMPORTANCE The present study provides the structural identification of the viable binding residues of the SARS-CoV-2 S2 fusion peptide region, which holds prime importance in the virus's host cell fusion and entry mechanism. The classical molecular mechanics simulations were set on values that mimic physiological standards for a good approximation of the dynamic behavior of selected drugs in biological systems. The drug molecules screened and analyzed here have relevant antiviral properties, which are reported here and which might hint toward their utilization in the coronavirus disease 2019 (COVID-19) pandemic owing to their attributes of binding to the fusion protein binding region shown in this study.

Aims To assess the prevalence of cardiovascular risk factors (CVRFs) and to identify the variables associated with CVRFs in a cohort of children and adolescents with Type 1 Diabetes. Methods 2021 subjects, 2-18 year-old, were recruited in 17 Italian Pediatric Diabetes Centers. Anthropometric, blood pressure, biochemical (HbA1c, lipid profile, ACR), insulin therapy, physical activity level, smoking and family socio-economic status data were collected. CVRFs prevalence and their distribution were analyzed according to age and binary logistic regression was performed with positivity for at least one major CVRF (BMI-SDS > +2SD, blood pressure > 90th percentile, LDL cholesterol>100 mg/dL) as dependent variable and age, duration of illness, gender, HbA1c and physical activity, as independent variables. Results The prevalence of CVFRs not at the recommended target was respectively: 32.5% one CVRF, 6.7% two CVRFs and 0.6% three CVRFs, with no significant differences across the 3 age groups (2-10, 10-15, 15-18 years). In the total sample, HbA1c and inadequate physical activity were associated with a higher probability of having at least one major CVRF. This probability was associated with physical activity in the 2-10-year-old group, with physical activity and HbA1c in the 10-15-year-old group and with HbA1c only in subjects older than 15 years. Conclusions More than 30% of subjects had at least a major CVRF. Early detection of CVRFs may be useful to enforce the therapeutic intervention in this subgroup, in order to reduce the risk to develop cardiovascular complications.