Potential inhibitors for SARS-CoV-2 Mpro from marine compounds

Preventing the biological activity of SARS-CoV-2 main protease using natural compounds is of great interest. In this context, using a combination of AutoDock Vina and fast pulling of ligand simulations, eleven marine fungi compounds were identified that probably play as highly potent inhibitors for preventing viral replication. In particular, four compounds including M15 (3-O-(6-O-α-l-arabinopyranosyl)-β-d-glucopyranosyl-1,4-dimethoxyxanthone), M8 (wailupemycins H), M11 (cottoquinazolines B), and M9 (wailupemycins I) adopted the predicted ligand-binding free energy of −9.87, −9.82, −9.62, and −9.35 kcal mol⁻¹, respectively, whereas the other adopted predicted ligand-binding free energies in the range from −8.54 to −8.94 kcal mol⁻¹. The results were obtained using a combination of Vina and FPL simulations. Notably, although, AutoDock4 adopted higher accurate results in comparison with Vina, Vina is proven to be a more suitable technique for rapidly screening ligand-binding affinity with a large database of compounds since it requires much smaller computing resources. Furthermore, FPL is better than Vina to classify inhibitors upon ROC-AUC analysis.

Preventing the biological activity of SARS-CoV-2 main protease using natural compounds is of great interest.     

Importance of water and intramolecular interaction governs substantial blue shift of Csp2–H stretching frequency in complexes between chalcogenoaldehydes and water

Geometrical structure, stability and cooperativity, and contribution of hydrogen bonds to the stability of complexes between chalcogenoaldehydes and water were thoroughly investigated using quantum chemical methods. The stability of the complexes increases significantly when one or more H₂O molecules are added to the binary system, whereas it decreases sharply going from O to S, Se, or Te substitution. The O–H⋯O H-bond is twice as stable as C_sp²–H⋯O and O–H⋯S/Se/Te H-bonds. It is found that a considerable blue-shift of C_sp²–H stretching frequency in the C_sp²–H⋯O H-bond is mainly determined by an addition of water into the complexes along with the low polarity of the C_sp²–H covalent bond in formaldehyde and acetaldehyde. The C_sp²–H stretching frequency shift as a function of net second hyperconjugative energy for the σ*(C_sp²–H) antibonding orbital is observed. Remarkably, a considerable C_sp²–H blue shift of 109 cm⁻¹ has been reported for the first time. Upon the addition of H₂O into the binary systems, halogenated complexes witness a decreasing magnitude of the C_sp²–H stretching frequency blue-shift in the C_sp²–H⋯O H-bond, whereas CH₃-substituted complexes experience the opposite trend.

The considerable blue shift of C_sp²–H stretching frequency.     

Characteristics of Epstein-Barr virus-associated gastric cancer: A study of 235 cases at a comprehensive cancer center in U.S.A

Background

Epstein-Barr virus (EBV) has been shown to be associated with gastric cancer. However, inconsistent findings have been reported regarding the distribution of EBV infected cells (in normal gastric epithelium vs. intestinal metaplastic cells vs. in neoplastic cells) and the characteristics of EBV-associated gastric cancer. Lymph node positive EBV-associated gastric cancer has not been systematically studied. The aims of this study were to evaluate EBV-associated gastric cancer, to assess the distribution of EBV infected cells including all positive lymph nodes, and to define the characteristics of EBV-associated gastric cancer.

Design

The study included primary gastric cancer patients who underwent surgical resection with no preoperative treatment at M.D. Anderson Cancer Center between 1987 and 2006. Formalin-fixed paraffin-embedded tissue from these resection specimens were assessed for EBV by in situ hybridization, the gold standard for EBV detection in tissue. EBV status was analyzed along with clinicopathologic parameters including age, gender, tumor type, lymph node status, and pathologic stage of the tumor.

Results

Among 235 patients, 12 had intranuclear expression of EBV. EBV staining was seen only in tumor cells and no detectable EBV was observed in normal gastric mucosa, intestinal metaplasia or stromal cells. Eight of 12 patients with EBV-associated gastric cancer had regional lymph node metastasis. Of note, metastatic tumor cells in all of the involved lymph nodes of these 8 cases contained EBV. The epidemiologic data showed 11 of the 12 patients with EBV-associated gastric cancer were men, ranging in age from 54 to 78 years (mean age, 60 years; median age, 62.1 years). The age distribution for non-EBV associated gastric cancer patients ranged from 21 to 93 years (mean age, 67 years; median age, 66.4 years).

Conclusion

Our study demonstrated that EBV is present exclusively in gastric cancer cells. The detection of EBV in tumor cells in all of the lymph nodes involved with metastatic gastric carcinoma suggests simultaneous replication of EBV and tumor cells. The predominantly male gender and relatively younger age observed for the EBV-infected gastric cancer cases suggest an association between this disease and other factors, such as life style.     

Radiotherapy omission after breast-conserving surgery is associated with reduced breast cancer-specific survival in elderly women with breast cancer

PURPOSE: To evaluate the effect of radiotherapy (RT) omission on survival in older breast cancer patients treated with breast-conserving surgery. METHODS: Data were analyzed for 4836 women aged 50 to 89 with T1-T2, N0-N1, M0 breast cancer. Tumor and treatment factors, relapse rates, and overall survival (OS) and breast cancer-specific survival (BCSS) were compared between women treated with and without RT in 3 age categories: 50 to 64 (n = 2398), 65 to 74 (n = 1665), and > or = 75 years (n = 773). RESULTS: Median follow-up was 7.5 years. Rates of RT omission significantly increased with advancing age (7%, 9%, and 26% in age 50-64, 65-74, and > or = 75 years respectively, P < .0001). RT omission was associated with significantly reduced local control, BCSS, and OS. Despite similar tumor characteristics and higher rates of systemic therapy use, women aged > or = 75 years were observed to have lower 5-year OS and BCSS when RT was omitted. CONCLUSION: These findings support the hypothesis that inadequate local therapy is associated with reduced survival in elderly women treated with breast-conserving therapy.