Bacterial infection is a frequent event in renal transplant recipients and often requires the use of antimicrobial agents. In this paper it is reported an evidence of pharmacokinetic interaction between clarithromycin and sirolimus in a kidney transplanted woman, suffering from pulmonary infection sustained by a bacterial pathogen, in particular Hemophilus Influenzae. In the present case report, the concomitant administration of clarithromycin and sirolimus determined impressive increase of sirolimus trough blood concentrations from 6.2 up to 54 ng/mL and this increase was associated with an acute impairment of renal function, almost completely reversed upon both drugs discontinuation. This drug-drug interaction is due to a likely inhibition of activity of both cytochrome P450 3A4 and P-glycoprotein. Although this interaction could be predicted, it represents the first reported clinical evidence.

The ambient air pollution (AAP) is ubiquitarian especially in the western countries and several studies have found correlations with different human pathologies (such as cardiovascular and respiratory diseases). In the last decades the scientific community has focused the studies on the possible effects of AAP on human reproduction, in particular on the pregnant women and birth outcomes. The researches have investigated the possible correlations between AAP and the effects of prenatal exposure and birth outcomes using several parameters such as low birth weight, intrauterine growth restriction, and preterm birth delivery. The authors found that the literature data are in conflict and do not reach univocal results. In fact, not all of the researches showed effects and correlations between AAP and birth outcomes and the studies are extremely various and do not use similar methods of analysis. Furthermore, the mechanisms of action are unclear. The possible difficulties in this matter should be the lack of an univocal guideline in the studies, the absence of the researches analyzing the particular internal composition of particulate matter, the possible overlap of short- and long-term exposure. In addition, the authors have verified the lack of studies of associations between the possible birth defects and ultrafine particulates (UFPs) able to move from pulmonary district to the circulatory system. Birth defects have a potential great impact on individual and public health because they may involve not only immediate but also future impairments of organs and/or metabolic functions. Therefore the authors suggest further studies that should be performed (a) using same guidelines, (b) analyzing not only the effects of the concentrations of the particulate matter but also of its particular internal composition, and (c) investigating the effects of UFPs on birth outcomes.

Canine coronavirus (CCoV), an alphacoronavirus belonging to the Coronaviridae family, is primarily associated with enteric infections in dogs. The ongoing evolution of coronaviruses through genetic recombination and mutation leads to the emergence of novel strains with increased pathogenicity, thereby raising the risk of cross-species transmission and spillover events. In this context, viral entry inhibitors represent a promising strategy, as they can serve as pivotal tools to prevent initial infection and subsequent viral replication. The S2 subunit of the spike (S) glycoprotein contains two heptad repeat regions (HRN and HRC), which play essential roles in the conformational changes required for viral fusion. In this study, we describe the design, synthesis, and functional evaluation of a peptide derived from the HRC domain of the CCoV S glycoprotein. First, we assessed the cytotoxicity of the CCoV-HRC peptide in two cell lines, HE293T and A72, and determined CC₅₀ values > 100 μM. At non-toxic concentrations, the peptide effectively blocked membrane fusion mediated by the CCoV S glycoprotein and significantly reduced viral infection, as demonstrated both in cell–cell fusion assays and in live virus experiments. These findings were supported by in silico docking and molecular dynamics simulations, which provided structural insight into the interaction between CCoV-HRC and the S fusion core. Then, molecular analyses were conducted to evaluate the expression of the gene encoding the viral S protein, confirming the antiviral potential of CCoV-HRC peptide. Overall, these findings provide a solid foundation for the development of peptide-based therapeutics to treat or prevent CCoV infections.

Peste des petits ruminants virus (PPRV) is a highly contagious morbillivirus causing severe disease in small ruminants, with major implications for global food security and ongoing eradication efforts. Despite the availability of effective vaccines, the absence of antiviral therapeutics represents a critical gap in outbreak control. Here, we describe the design and in vitro characterization of a synthetic peptide derived from the heptad repeat C (HRC) region of the PPRV fusion (F) protein as a novel viral entry inhibitor. The HRC peptide potently inhibited PPRV F/H-mediated membrane fusion in a dose-dependent manner, with IC₅₀ values of 11.80 μM and 18.11 μM for SLAM/CD150- and nectin-4-dependent entry, respectively. Consistently, the peptide blocked viral entry in a vesicular stomatitis virus (VSV)-based pseudovirus system (IC₅₀ = 14.5 μM). Antiviral activity was further confirmed using a replicative morbillivirus model (canine distemper virus), where significant inhibition of infection was observed in both co-treatment and virus pre-treatment conditions. Notably, the combination with a fusion inhibitory compound (FIP) resulted in synergistic antiviral activity (FICI = 0.44), highlighting the potential of dual-targeting strategies. Biophysical analyses revealed a strong α-helical propensity in membrane-mimetic environments and high stability in human serum. Molecular docking and dynamics simulations indicated that the HRC peptide stabilizes the F protein by bridging critical domains through a persistent hydrogen-bond network, thereby preventing the conformational rearrangements required for membrane fusion. Collectively, these findings provide the first evidence that HRC-derived peptides can effectively inhibit PPRV entry and support their development as antiviral agents to complement current eradication strategies.