Objective To clarify the diagnostic value of salivary gland ultrasonography in Sj(o)gren's syndrome (SS),and its correlation with the disease activity index and important organs involvement were analyzed.Methods A total of 116 patients with SS were involved,including 71 cases of primary SS and 45cases of secondary SS.Ultrasonography examination of major salivary glands was conducted for these patients,at the same time the clinical data including inflammatory parameters,the immunological parameter and the involved systems were collected.Ultrasonography examination was conducted in 49 cases as the control group.Use t test,x2test and analysis of variance for statistical analysis.Results The positive rate of salivary gland uhrasonography in SS (56/116,48.3％) was significantly higher than that of the normal control groups (1/49,2.0％),(The chi-square value was 32.57,P＜0.05),the sensitivity of salivary gland ultrasonography in primary SS (62.0％) was obviously higher than secondary SS (27％),(The Chi-square value was 13.75,P＜0.01).The specificity of salivary gland ultrasonography was 98％.The scores of salivary gland ultrasonography had shown positive correlation with the erythrocyte sedimentation rate,the levels of Immunoglobulin (Ig)G,and RF(r=0.234,0.353,0.176;P=0.002,0.000,0.013),and negative correlation with the white blood cell count (r=-0.292,P=0.000).Conclusion Salivary gland ultra-sonography provides additional evidence for the diagnosis of SS,particularly in primary SS groups.The scores of ultrasonography are correlated with inflammatory biomarkers,indicating that salivary gland ultrasonography is related to disease activity.

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection. Herein, we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective.

The main protease (M^pro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent M^pro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent M^pro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent M^pro inhibitors with desirable properties have been developed based on available crystal structures of M^pro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^pro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent M^pro inhibitors are also discussed.