NHE inhibitors (Medicure)

Inspired by our earlier findings regarding neuraminidase (NA) inhibitors interacting with 150-cavity or 430-cavity of NA, sixteen novel polyheterocyclic NA inhibitors with 1,3,4-oxadiazole thioetheramide as core backbone were designed and synthesized based on the lead compound ZINC13401480. Of the synthesized compounds, compound N5 targeting 150-cavity exerts the best inhibitory activity against the wild-type H5N1 NA, with IC₅₀ value of 0.14 μM, which is superior to oseltamivir carboxylate (OSC) (IC₅₀ = 0.31 μM). Compound N10 targeting 430-cavity exhibits the best activity against the H5N1-H274Y mutant NA. Although the activity of N10 is comparable to that of OSC for wild-type H5N1 inhibition, it is approximately 60-fold more potent than OSC against the H274Y mutant, suggesting that it is not easy for the virus to develop drug resistance and is attractive for drug development. N10 (EC₅₀ = 0.11 μM) also exhibits excellent antiviral activity against H5N1, which is superior to the positive control OSC (EC₅₀ = 1.47 μM). Molecular docking study shows that the occupation of aromatic fused rings and oxadiazole moiety at the active site and the extension of the substituted phenyl to the 150-cavity or 430-cavity make great contributions to the good potency of this series of polyheterocyclic NA inhibitors. Some advancements in the discovery of effective target-specific NA inhibitors in this study may offer some assistance in the development of more potent anti-influenza drugs.

To compare the efficacy of neuroendoscopic hematoma evacuation (NHE) and burr hole craniotomy (BHC) for treating septated chronic subdural hematoma (sCSDH) and analyze the technical advantages of NHE in sCSDH treatment by data analysis.

This study recruited 77 patients with sCSDH According to the type of operation, the patients were divided into NHE (n = 45) or BHC (n = 32) groups. Clinical data were retrospectively analyzed to evaluate and compare the efficacy of NHE and BHC for treating sCSDH.

NHE demonstrated higher complete hematoma clearance and postoperative midline recovery rates and shorter subdural drainage and postoperative bed rest durations compared with BHC (P < 0.05). The average NHE time (72.27 ± 18.27 minutes) was longer than that of BHC (54.91 ± 16.04 minutes) (P < 0.05). The average follow-up period was 30.9 (range, 7-51) months. The results revealed that 1 and 12 cases recurred in the NHE (2.2%) and BHC (18.8%) groups, respectively (P < 0.05). Additionally, a statistically significant difference in the Modified Rankin Scale scores of the 2 groups was observed 6 months after the operation (P < 0.05). During the follow-up period, neither group demonstrated any obvious operative complications.

NHE is more effective than BHC for treating sCSDH and is worth popularizing on a large scale; however, ways to better deal with the outer membrane of hematoma warrant further consideration.