Multiscale Hybrid Modeling of Proteins in Solvent: SARS-CoV2 Spike Protein as Test Case for Lattice Boltzmann – All Atom Molecular Dynamics Coupling

Physiological solvent flows surround biological structures triggering therein collective motions. Notable examples are virus/host-cell interactions and solvent-mediated allosteric regulation. The present work describes a multiscale approach joining the Lattice Boltzmann fluid dynamics (for solvent flows) with the all-atom atomistic molecular dynamics (for proteins) to model functional interactions between flows and molecules. We present, as an applicative scenario, the study of the SARS-CoV-2 virus spike glycoprotein protein interacting with the surrounding solvent, modeled as a mesoscopic fluid. The equilibrium properties of the wild-type spike and of the Alpha variant in implicit solvent are described by suitable observables. The mesoscopic solvent description is critically compared to the all-atom solvent model, to quantify the advantages and limitations of the mesoscopic fluid description. ©2023 Global-Science Press.

[Antimicrobial stewardship program during the COVID-19 pandemic]

In spite of the low frequency of COVID-19 associated bacterial coinfections, the rate of empiric antibiotic use varies between 70% and 90%. The primary objective of this study was to evaluate the impact of an antimicrobial stewardship program (ASP) on COVID-19 patients. The study design was an interrupted time series, assessing prevalence of antibiotic use, adequacy of treatment and antimicrobial consumption in adult patients hospitalized with COVID before the COVID-ASP implementation in June 2020, and on three subsequent periods (P2 in August 2020, P3 in October 2020 and P4 in June 2021). One hundred and one patients were included. Moderate and severe disease was more frequent in P2, P3, and P4 periods (p < 0.001). After the implementation we observed a significant reduction on ATM use (61% vs. 41% vs. 31.1% vs. 8.1%, p < 0.001), and macrolid combination therapy (17.3% vs. 19.2% vs. 10.8% vs. 1.4%, p = 0.03), and an increase of adequate use (37.5% vs. 46.9% vs. 69.9% vs. 66.6%, p = 0.039). Antimicrobial consumption by period in days of therapy (DOT)/1000 patient-day was 347.9 vs. 272.8 vs. 134.29 vs. 43.6 (p <0.001). We did not find any difference in intensive care unit transfer or mortality. COVID-ASP implementation was an effective strategy to reduce antimicrobial consumption and optimize antibiotic indications without affecting morbidity or mortality.