Background: The risk factors, disease characteristics, severity, and mortality of COVID-19 are unclear, particularly in Egypt. Objective: The objective was to analyze the patients' characteristics, hematological, biochemical, and chest imaging findings among the cohort of patients with COVID-19 in Egypt and also to shed light on the predictors of COVID-19 severity. Patients and Methods: A retrospective study was conducted on 66 patients with COVID-19 in Egypt. Medical history, imaging data (CT chest findings), and measured hematological and biochemical parameters at diagnosis were recorded in the form of complete blood counts and differential counts; CRP, ESR, serum ferritin, creatinine, and liver function tests. Results of realtime reverse transcription-polymerase chain reaction (rRT-PCR) for detection of SARS-CoV-2 RNA at diagnosis and during follow up of these patients were also recorded. Results: The study included 36 patients with mild to moderate COVID-19 and 30 patients with severe/critical infection. There was a significant older age among severe (62.6 years old ±10.1SD) than mild to moderate infection (55.5 ± 10.1) (p˂0.05). Fever, dry cough, dyspnea, and sore throat malaise were highly frequent among COVID-19 patients, while headache and diarrhea were the least frequently occurring manifestations. All included cases (30 patients, 100%) with severe COVID-19 showed crazy-paving appearance (in the form of reticular and/or interlobular septal thickening) with or without GGO. There were significantly lower mean values of WBCs, lymphocytic count, total protein, and albumin among the severely infected than those who had mild to moderate COVID-19 infection, p˂0.05 for all. Additionally, there were significantly higher mean values of CRP, ESR, ferritin, ALT, and AST among patients with severe/critical COVID-19 when compared with those having mild to moderate COVID-19, p˂0.05 for all. Conclusion: Among the studied demographic, clinical, hematological, biochemical, and imaging data, dyspnea, diabetes mellitus, lymphopenia, raised CRP, ESR, ferritin, ALT, AST, low albumin, and presence of CT chest findings could be considered as predictors for COVID-19 severity using binary logistic regression analysis.

The reaction of 5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thione 3 with formaldehyde solution and primary aromatic amines or 1-substituted piperazines, in ethanol at room temperature yielded the corresponding N-Mannich bases 3-arylaminomethyl-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 4a–l or 3-[(4-substituted piperazin-1-yl)methyl]-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 5a–d, respectively. The in vitro inhibitory activity of compounds 4a–l and 5a–d was assessed against pathogenic Gram-positive, Gram-negative bacteria, and the yeast-like pathogenic fungus Candida albicans. The piperazinomethyl derivatives 5c and 5d displayed broad-spectrum antibacterial activities the minimal inhibitory concentration (MIC) 0.5–8 μg/mL) and compounds 4j, 4l, 5a, and 5b showed potent activity against the tested Gram-positive bacteria. In addition, the anti-proliferative activity of the compounds was evaluated against prostate cancer (PC3), human colorectal cancer (HCT-116), human hepatocellular carcinoma (HePG-2), human epithelioid carcinoma (HeLa), and human breast cancer (MCF7) cell lines. The optimum anti-proliferative activity was attained by compounds 4l, 5a, 5c, and 5d.

The vascular endothelial growth factor receptor 2 (VEGFR-2) is largely recognized as a potent therapeutic molecular target for the development of angiogenesis-related tumor treatment. Tumor growth, metastasis and multidrug resistance highly depends on the angiogenesis and drug discovery of the potential small molecules targeting VEGFR-2, with the potential anti-angiogenic activity being of high interest to anti-cancer research. Multiple small molecule inhibitors of the VEGFR-2 are approved for the treatment of different type of cancers, with one of the most recent, tivozanib, being approved by the FDA for the treatment of relapsed or refractory advanced renal cell carcinoma (RCC). However, the endogenous and acquired resistance of the protein, toxicity of compounds and wide range of side effects still remain critical issues, which lead to the short-term clinical effects and failure of antiangiogenic drugs. We applied a combination of computational methods and approaches for drug design and discovery with the goal of finding novel, potential and small molecule inhibitors of VEGFR2, as alternatives to the known inhibitors’ chemical scaffolds and components. From studying several of these compounds, the derivatives of pyrido[1,2-a]pyrimidin-4-one and isoindoline-1,3-dione in particular were identified.

A selective triazole-based COX-2 inhibitor, 4-(4-chlorophenyl)-3-[(4-fluorobenzyl)sulfanyl]-5-(thiophen-2-yl)-4 H -1,2,4-triazole, C 19 H 13 ClFN 3 S 2 , has been synthesized, and its crystal structure was determined at 150 K. Single-crystal X-ray diffraction analysis revealed that the thiophene ring was disordered over two orientations. The crystal structure is stabilized by weak hydrogen and chalcogen bonds and unorthodox F···π and S···C(π) contacts. These noncovalent interactions cooperatively generate the supramolecular self-assembly in the crystalline state. The Hirshfeld surface and its associated two-dimensional (2D)-fingerprint plots were obtained to analyze the role of different noncovalent interactions in the crystal packing. Further, the enrichment ratio was obtained from different atom···atom pairs to calculate the propensity of these pairs to form noncovalent interactions. The strength of different dimeric motifs formed in the crystal structure and lattice energies was calculated by the PIXEL method. Furthermore, the topological analysis of the charge density of intermolecular interactions was described. A CSD survey of C–H···F hydrogen bond, C–S···Cl chalcogen bond, and unorthodox nonbonded contacts (F···π and S···C(π)) is presented. The title compound possesses selective inhibitory activity against human COX-2 enzyme rather than COX-1. The quantum mechanics (QM) polarized ligand docking analysis was used to predict the binding pose and study the title compound’s selectivity against COX-1/2 enzymes.

A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione 4a–e , 1,3,4-thiadiazole aryl urea 6a–d, and cyanothiouracil moieties 8a–d was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, 4a was the most potent showing IC50 of 5.61, 7.92, and 3.84 µM, respectively. Furthermore, compounds 4e and 8a proved to have strong impact on breast cancer cell line with IC50 of 6.11 and 10.86 µM, respectively. The three compounds showed a good safety profile towards normal WI-38 cells. Flow cytometric analysis of the three compounds in MCF-7 cells revealed that compounds 4a and 4c inhibited cell population in the S phase, whereas 8a inhibited the population in the G1/S phase. The most promising compounds were subjected to a VEGFR-2 inhibitory assay where 4a emerged as the best active inhibitor of VEGFR-2 with IC50 91 nM, compared to 53 nM for SOR. In silico analysis showed that the three new hybrids succeeded to link to the active site like the co-crystallized inhibitor SOR.