The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

OBJECTIVETo determine the tricuspid annular plane systolic excursion (TAPSE) using M-mode echocardiography, and to evaluate the right ventricular systolic function in patients with pneumoconiosis.

METHODSOne hundred and eighty-three patients with pneumoconiosis were enrolled as subjects, and one hundred and ninety-nine healthy volunteers were used as controls. According to the types of ventilation dysfunction, patients were divided into four groups: normal type, obstructive type, restrictive type, and mixed type. In the apex four-chamber sections, the displacement of tricuspid annular plane on the right ventricular free wall side was measured from end-diastole to end-systole using M-mode echocardiography.

RESULTSThe average TAPSE in the pneumoconiosis group was significantly lower than that in the control group (18.61 ± 3.08 vs 22.38 ± 3.03 mm, P < 0.01). Along with the progression of pneumoconiosis, the TAPSE values in patients with stage I, II, and III pneumoconiosis were significantly decreased compared with those in the control group (P < 0.01). The TAPSE values in patients diagnosed with normal, obstructive, restrictive, and mixed types of pneumoconiosis in pulmonary function tests were all significantly lower than those in the control group (P < 0.01). Among all patients, patients with mixed type of pneumoconiosis had the most significant reduction in the TAPSE.

CONCLUSIONThe TAPSE is substantially decreased in patients with pneumoconiosis and further decreased along with the progression of pneumoconiosis. Measurement of the TAPSE is an easy way to evaluate the right ventricular systolic function in patients with pneumoconiosis.

Case-Control Studies ; Echocardiography ; Humans ; Pneumoconiosis ; physiopathology ; Systole ; Tricuspid Valve ; physiopathology ; Ventricular Function, Right

In this paper, adriamycin-carboxymethyldextran magnetic nanoparticles (ADR-CMD MNPs) were prepared. After i.v. administration in mice, acute toxicity, cumulative toxicity and the distribution profiles of heart were studied both for free adriamycin(ADR) and ADR-CMD MNPs. The results showed conjugation with CMD MNPs, the acute toxicity of ADR was decreased significantly, the LD50 value of ADR-CMD MNPs was 5.06 times as high as that of the free ADR. Altogether, the cumulative toxicity of conjugate MNPs is significantly decreased as expressed by the mortality, the loss for both weight and leucocyte after repeated injection. Tissue distribution studies show the reduced cardiac uptake of ADR after i.v. which possibly contributes to minimizing the cardiotoxic effect of ADR.
Animals ; Dextrans ; Doxorubicin ; administration & dosage ; pharmacokinetics ; toxicity ; Drug Carriers ; Drug Delivery Systems ; Female ; Injections, Intravenous ; Magnetics ; Male ; Mice ; Myocardium ; metabolism ; Tissue Distribution