Nanobiotics and the One Health Approach: Boosting the Fight against Antimicrobial Resistance at the Nanoscale.

Antimicrobial resistance (AMR) is a growing public health concern worldwide, and it poses a significant threat to human, animal, and environmental health. The overuse and misuse of antibiotics have contributed significantly and others factors including gene mutation, bacteria living in biofilms, and enzymatic degradation/hydrolyses help in the emergence and spread of AMR, which may lead to significant economic consequences such as reduced productivity and increased health care costs. Nanotechnology offers a promising platform for addressing this challenge. Nanoparticles have unique properties that make them highly effective in combating bacterial infections by inhibiting the growth and survival of multi-drug-resistant bacteria in three areas of health: human, animal, and environmental. To conduct an economic evaluation of surveillance in this context, it is crucial to obtain an understanding of the connections to be addressed by several nations by implementing national action policies based on the One Health strategy. This review provides an overview of the progress made thus far and presents potential future directions to optimize the impact of nanobiotics on AMR.

Structural analysis of viral infectivity factor of HIV type 1 and its interaction with A3G, EloC and EloB.

BACKGROUND: The virion infectivity factor (Vif) is an accessory protein, which is essential for HIV replication in host cells. Vif neutralizes the antiviral host protein APOBEC3 through recruitment of the E3 ubiquitin ligase complex. METHODOLOGY: Fifty thousand Vif models were generated using the ab initio relax protocol of the Rosetta algorithm from sets of three- and nine-residue fragments using the fragment Monte Carlo insertion-simulated annealing strategy, which favors protein-like features, followed by an all-atom refinement. In the protocol, a constraints archive was used to define the spatial relationship between the side chains from Cys/His residues and zinc ions that formed the zinc-finger motif that is essential for Vif function. We also performed centroids analysis and structural analysis with respect to the formation of the zinc-finger, and the residue disposal in the protein binding domains. Additionally, molecular docking was used to explore details of Vif-A3G and Vif-EloBC interactions. Furthermore, molecular dynamics simulation was used to evaluate the stability of the complexes Vif-EloBC-A3G and Vif-EloC. PRINCIPAL FINDINGS: The zinc in the HCCH domain significantly alters the folding of Vif and changes the structural dynamics of the HCCH region. Ab initio modeling indicated that the Vif zinc-finger possibly displays tetrahedral geometry as suggested by Mehle et al. (2006). Our model also showed that the residues L146 and L149 of the BC-box motif bind to EloC by hydrophobic interactions, and the residue P162 of the PPLP motif is important to EloB binding. CONCLUSIONS/SIGNIFICANCE: The model presented here is the first complete three-dimensional structure of the Vif. The interaction of Vif with the A3G protein and the EloBC complex is in agreement with empirical data that is currently available in the literature and could therefore provide valuable structural information for advances in rational drug design.