The SARS-CoV-2 spike protein is pivotal in the COVID-19 virus’s life cycle, facilitating viral attachment to host cells. It is believed that targeting this viral protein could be key to developing effective COVID-19 prophylactics. Using in silico techniques, this study sought to virtually screen for compounds from the literature that strongly bind and disrupt the stability of the HSPA8–spike protein complex. To evaluate the interactions between the individual proteins and the protein complex attained from protein–protein docking using BioLuminate, molecular docking was performed using the Maestro Schrodinger Suite. The screened small molecules met all bioavailability conditions, Lipinski’s and Veber’s rules, and the required medicinal chemistry properties. Protein–protein docking of the spike protein and HSPA8 identified the optimal pose with a PIPER cluster size of 65, a PIPER pose energy of −748.301 kcal/mol, and a PIPER pose score of −101.189 kcal/mol. Two small molecules, NSC36398 and NSC281245, showed promising docking scores against the spike protein individually and in a complex with HSPA8. NSC36398 had a docking score of −7.934 kcal/mol and a binding free energy of −39.52 kcal/mol with the viral spike protein and a docking score of −8.029 kcal/mol and binding free energy of −38.61 with the viral protein in complex with HSPA8, respectively. Mevastatin had a docking score of −5.099 kcal/mol and a binding free energy of −44.49 kcal/mol with the viral protein and a docking score of −5.285 kcal/mol and binding free energy of −36.65 kcal/mol with the viral protein in complex with HSPA8, respectively. These results, supported by extensive 2D interaction diagrams, suggest that NSC36398 and NSC281245 are potential drug candidates targeting SARS-CoV-2 spike protein.

Lithium remains the preferred Food and Drug Administration- (FDA-) approved psychiatric drug for treatment of bipolar disorders since its medical establishment more than half a century ago. Recent studies revealed a promising role for lithium in the regulation of inflammation, oxidative stress, and neurodegeneration albeit unclear about its exact mode of action. Thus, the intention of this study is to delineate the regulatory mechanisms of lithium on oxidative stress in lipopolysaccharide- (LPS-) activated macrophages by evaluating its effects on nuclear factor-κB (NF-κB) activity and mRNA expression of multiple oxidative stress-related NF-κB genes. Raw 264.7 macrophages were treated with up to 10 mM lithium, and no change in cell proliferation, viability, growth, and cell adhesion was observed in real time. Pretreatment with low doses of lithium was shown to reduce nitric oxide (NO) production in LPS-activated macrophages. A reduced internal H₂DCFDA fluorescence intensity, indicative of reduced reactive oxygen species (ROS) production, was observed in LPS-activated Raw 264.7 macrophages treated with lithium. Lithium has been shown to lower the production of the chemokine RANTES; furthermore, this inhibitory action of lithium has been suggested to be independent of glycogen synthase kinase-3 β (GSK3β) activity. It is shown here that lithium modulates the expression of several inflammatory genes including IκB-α, TRAF3, Tollip, and NF-κB1/p50 which are regulators of the NF-κB pathway. Moreover, lithium inhibits NF-κB activity by lowering nuclear translocation of NF-κB in LPS-activated macrophages. This is the first study to associate Tollip, Traf-3, and IκB-α mRNA expression with lithium effect on NF-κB activity in LPS-activated Raw 264.7 macrophages. Although these effects were obtained using extratherapeutic concentrations of lithium, results of this study provide useful information towards understanding the mode of action of lithium. This study associates lithium with reduced oxidative stress in LPS-activated Raw 264.7 macrophages and further suggests candidate molecular targets for the regulation of oxidative stress-related diseases using lithium beyond bipolar disorders.

Introduction: Rift Valley fever virus (RVFV) is a zoonotic life-threatening viral infection endemic across sub-Saharan African countries and the Arabian Peninsula; however, there is a growing panic of its spread to non-endemic regions. This viral infection triggers a wide spectrum of symptoms that span from fibril illnesses to more severe symptoms such as haemorrhagic fever and encephalitis. These severe symptoms have been associated with dysregulated immune response propagated by the virulence factor, non-structural protein (NSs). Thus, this study investigates the effects of lithium on NF-κB translocation and RFVF-induced inflammation in Raw 264.7 macrophages. Methods: The supernatant from RVFV-infected Raw 264.7 cells, treated with lithium, was examined using an ELISA assay kit to measure levels of cytokines and chemokines. The H₂DCF-DA and DAF-2 DA florigenic assays were used to determine the levels of ROS and RNS by measuring the cellular fluorescence intensity post RVFV-infection and lithium treatment. Western blot and immunocytochemistry assays were used to measure expression levels of the inflammatory proteins and cellular location of the NF-κB, respectively. Results: Lithium was shown to stimulate interferon-gamma (IFN-γ) production as early as 3 h pi. Production of the secondary pro-inflammatory cytokine and chemokine, interleukin-6 (IL-6) and regulated on activation, normal T cell expressed and secreted (RANTES), were elevated as early as 12 h pi. Treatment with lithium stimulated increase of production of tumor necrosis factor-alpha (TNF-α) and Interleukin-10 (IL-10) in RVFV-infected and uninfected macrophages as early as 3 h pi. The RVFV-infected cells treated with lithium displayed lower ROS and RNS production as opposed to lithium-free RVFV-infected control cells. Western blot analyses demonstrated that lithium inhibited iNOS expression while stimulating expression of heme oxygenase (HO) and IκB in RVFV-infected Raw 264.7 macrophages. Results from immunocytochemistry and Western blot assays revealed that lithium inhibits NF-κB nuclear translocation in RVFV-infected cells compared to lithium-free RVFV-infected cells and 5 mg/mL LPS controls. Conclusion: This study demonstrates that lithium inhibits NF-kB nuclear translocation and modulate inflammation profiles in RVFV-infected Raw 264.7 macrophage cells.

Despite major advancements in the development of various chemotherapeutic agents, treatment for lung cancer remains costly, ineffective, toxic to normal non-cancerous cells, and still hampered by a high level of remissions. A novel cohort of quinoxaline derivatives designed to possess a wide spectrum of biological activities was synthesized with promising targeted and selective anticancer drug activity. Hence, this study was aimed at determining in vitro anticancer activity effects of a newly synthesized class of 3-(quinoxaline-3-yl) prop-2-ynyl quinoxaline derivatives on A549 lung cancer cells. An assessment of the quinoxaline derivatives ferric reducing power, free radical scavenging activity, cytotoxic activity, and ability to induce reactive oxygen species (ROS) production was performed using the Ferric Reducing Antioxidant Power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and 2’,7’-dichlorodihydrofluorescein diacetate (H₂DCFDA) assays, respectively. The ability of the quinoxaline derivatives to induce apoptosis in A549 cells was assessed using the Acridine Orange/Ethidium Bromide (AO/EB) and Annexin V-FITC/Dead Cell Assay. Of the four quinoxaline derivatives tested, 3-(quinoxaline-3-yl) prop-2-ynyl methanosulphate (LA-39B) and 3-(quinoxaline-3-yl) prop-2-yn-1-ol (LA-55) displayed a dose-dependent reducing power, free-radical scavenging activity, inhibition of cell viability, and stimulation of ROS production which was accompanied by induction of apoptosis in A549 lung cancer cells. None of the quinoxaline derivatives induced cell death or ROS production in non-cancerous Raw 267.4 macrophage cells. Cytotoxicity was observed in A549 lung cancer, HeLa cervical cancer, and MCF-7 breast cancer cells albeit inhibition was more pronounced in A549 cells. The results of the study suggest that 3-(quinoxaline-3-yl) prop-2-ynyl methanosulphate and 3-(quinoxaline-3-yl) prop-2-yn-1-ol induce apoptotic cell death in A549 lung cancer cells.

Medicinal plants have been identified as a feasible avenue for the development of new potent antidiabetic agents. The phytoconstituent compositions of differentToona ciliataandSchkuhria pinnataextracts were determined and quantified using standard chemical methods after exhaustive extraction. Thereafter, their antioxidant and antiglycation potentials were spectrophotometrically determined. The cytotoxicity profiles of the extracts on C2C12 cells were determined using the MTT assay.Toona ciliatamethanol extract resulted in the highest percentage yield (20.83%) and high total phenols and flavonoids content in the methanol and acetone extracts compared toS. pinnataextracts. The acetone extract ofT. ciliatashowed good activity in the DPPH scavenging and FRAP assays with EC₅₀values of 1.90 mg/ml and 5.26 mg/ml, respectively. Arbutin’s antiglycation ability was outperformed by treatments with the methanol, acetone, and hexane extract ofT. ciliatawhich resulted in 2.49%, 2.79%, and 2.56% glycation, respectively. The hexane extract ofT. ciliatawas less toxic to C2C12 cells as compared to the other extracts with CC₅₀value of 402.16μg/ml. Only the hexane extract ofS. pinnataresulted in glucose utilisation of 28.56% which was higher than that of insulin (26.06%) after 6 hours and is therefore considered as the most potent extract with hypoglycaemic potential in this study. Studies are ongoing aimed at identifying drug candidates in this extract that may be employed in the development of hypoglycaemic, antioxidant, and antiglycation agents.