Discovery of novel polyheterocyclic neuraminidase inhibitors with 1,3,4-oxadiazole thioetheramide as core backbone.

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.

[Aerosol optical thickness of the atmospheric aerosol over Taihu Lake and its features: results of in-site measurements].

Based on the data measured in situ by an automatic sun tracking photometer (CE-318), the aerosol optical thickness (AOT) and the corresponding Angström coefficient alpha of the atmospheric aerosol over Taihu Lake from November 2005 to October 2010 were collected. The results showed that high values of AOT over Taihu Lake were measured in summer (June to July) whereas low values were detected in autumn and winter (October to January). However, the low and high values of a appeared in spring (March to April) and in autumn (September to November), respectively. The variations of AOT and a over Taihu Lake may be related to weather patterns in this region. Based on the frequency distribution, AOT (500 nm) had only one peak value, with a maximum frequency of 0.4-0.6 and a yearly average value of 0.80, accounting for 26% of the total sample. Calculated from the mean AOT (500 nm), the solar radiation reduction was reduced by at least 50% by the atmospheric aerosol, resulting in more turbid atmosphere in this region and consequently heavy fog and haze. There were two peak values of the Angström coefficient alpha, with the maximum frequency ranging from 1.1-1.3 and 1.3-1.5 and a yearly average value of 1.17, accounting for 30% of the total sample. Significant variations were also observed in the daily average values of AOT (500 nm) and a, indicating the coexistence of different types of aerosols over Taihu Lake. The mean value of AOT (500 nm) declined when a increased. To sum up, values of AOT (500 nm) over Taihu Lake changed greatly with time, and the aerosol should be classified as an urban-industrial aerosol.