Biochemistry Research International

Despite treatments and vaccinations, it remains difficult to develop naturally occurring COVID-19 inhibitors. Here, our main objective is to find potential lead compounds from the retrieved alkaloids with antiviral and other biological properties that selectively target the main SARS-CoV-2 protease (M^pro), which is required for viral replication. In this work, 252 alkaloids were aligned using Lipinski’s rule of five and their antiviral activity was then assessed. The prediction of activity spectrum of substances (PASS) data was used to confirm the antiviral activities of 112 alkaloids. Finally, 50 alkaloids were docked with M^pro. Furthermore, assessments of molecular electrostatic potential surface (MEPS), density functional theory (DFT), and absorption, distribution, metabolism, excretion, and toxicity (ADMET) were performed, and a few of them appeared to have potential as candidates for oral administration. Molecular dynamics simulations (MDS) with a time step of up to 100 ns were used to confirm that the three docked complexes were more stable. It was found that the most prevalent and active binding sites that limit M^pro’sactivity are PHE294, ARG298, and GLN110. All retrieved data were compared to conventional antivirals, fumarostelline, strychnidin-10-one (L-1), 2,3-dimethoxy-brucin (L-7), and alkaloid ND-305B (L-16) and were proposed as enhanced SARS-CoV-2 inhibitors. Finally, with additional clinical or necessary study, it may be able to use these indicated natural alkaloids or their analogs as potential therapeutic candidates.

Objective. Oral tongue squamous cell carcinoma (OTSCC) and buccal squamous cell carcinoma (BSCC) are the first and second leading causes of oral cancer, respectively. OTSCC and BSCC are associated with poor prognosis in patients with oral cancer. Thus, we aimed to indicate signaling pathways, Gene Ontology terms, and prognostic markers mediating the malignant transformation of the normal oral tissue to OTSCC and BSCC. Methods. The dataset GSE168227 was downloaded and reanalyzed from the GEO database. Orthogonal partial least square (OPLS) analysis identified common differentially expressed miRNAs (DEMs) in OTSCC and BSCC compared to their adjacent normal mucosa. Next, validated targets of DEMs were identified using the TarBase web server. With the use of the STRING database, a protein interaction map (PIM) was created. Using the Cytoscape program, hub genes and clusters within the PIM were shown. Next, gene-set enrichment analysis was carried out using the g:Profiler tool. Using the GEPIA2 web tool, analyses of gene expression and survival analysis were also performed. Results. Two DEMs, including has-miR-136 and has-miR-377, were common in OTSCC and BSCC ( value <0.01; |Log2 FC| > 1). A total of 976 targets were indicated for common DEMs. PIM included 96 hubs, and the upregulation of EIF2S1, CAV1, RAN, ANXA5, CYCS, CFL1, MYC, HSP90AA1, PKM, and HSPA5 was significantly associated with a poor prognosis in the head and neck squamous cell carcinoma (HNSCC), while NTRK2, HNRNPH1, DDX17, and WDR82 overexpression was significantly linked to favorable prognosis in the patients with HNSCC. “Clathrin-mediated endocytosis” was considerably dysregulated in OTSCC and BSCC. Conclusion. The present study suggests that has-miR-136 and has-miR-377 are underexpressed in OTSCC and BSCC than in normal oral mucosa. Moreover, EIF2S1, CAV1, RAN, ANXA5, CYCS, CFL1, MYC, HSP90AA1, PKM, HSPA5, NTRK2, HNRNPH1, DDX17, and WDR82 demonstrated prognostic markers in HNSCC. These findings may benefit the prognosis and management of individuals with OTSCC/BSCC. However, additional experimental verification is required.

In recent years, the potential of pathogenic bacteria to acquire resistance to a variety of antimicrobial drugs has developed significantly due to the indiscriminate exposure of a number of antibiotic compounds. The purpose of this study is to determine the antibacterial capabilities and activities of crude Pleurotus ostreatus extracts against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Neisseria gonorrhoeae (ATCC 49926), and nine multidrug-resistant clinical isolates of Neisseria gonorrhoeae. All of these isolates exhibited sensitivity to azithromycin and ceftriaxone, while the majority of antibiotic resistance was seen against penicillin G, sulphonamide, and ciprofloxacin. Fifty percent of the isolates exhibited absolute resistance to both sulphonamide and ciprofloxacin, whereas 40% of the isolates displayed absolute resistance to penicillin G. The antibacterial activity of P. ostreatus extracts examined in this investigation varied within the same species of microorganisms. Extract B and D, extracted in the presence of 20% wheat bran bagasse and 20% maize flour bagasse, respectively, had exceptional antibacterial activity against all target isolates examined. We observed the lowest concentration of antibacterial agent required to inhibit the target bacteria to be between 1 × 10⁻³ mg/ml and 1 × 10⁻⁶ mg/ml with an estimated probability of 0.30769, a lower 95% confidence interval (CI) of 0.126807, an upper 95% CI of 0.576307, an estimated probability of 0.15385, a lower 95% CI of 0.043258, and an upper 95% CI, respectively. The MBC of 1 × 10⁻³ mg/ml was seen to eliminate 31% of the target bacteria. This dose was the most inhibitive. The antibacterial activity of all the extracts examined in the current study exhibited some degree of efficacy against both clinical isolates and standard strains. However, the majority of clinically isolated bacteria exhibited greater resistance to the extracts.

Essential oils are known to possess many biological properties such as antimicrobial and antioxidant activities. Plumeria alba flowers are used in traditional remedies for diarrhea, cough, fever, and asthma treatment. This work evaluated the chemical composition and the biological activities of essential oils obtained from the flowers and leaves of Plumeria alba. The essential oils were extracted using the Clevenger-type apparatus and characterized using GC-MS. In the flower essential oil, a total of 17 compounds were identified, with linalool (23.91%), α-terpineol (10.97%), geraniol (10.47%), and phenyl ethyl alcohol (8.65%) being abundant. In the leaf essential oil, a total of 24 compounds were identified, with benzofuran, 2,3-di, hydro-(3.24%), and muurolol (1.40%) being present. Antioxidant activities were assessed using hydrogen peroxide scavenging, phosphomolybdenum, and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assays. Antimicrobial activities were assessed through a microdilution assay. The essential oil showed antimicrobial activity against test microorganisms with minimum inhibitory concentrations ranging from 25.0 to 50.0 mg/mL. Biofilm inhibition ranged from 27.14 ± 1.0 to 58.99 ± 0.6 mg/mL. The essential oil exhibited total antioxidant capacities which ranged from 17.5 μg/g AAE to 83 μg/g AAE in the phosphomolybdenum assay. The IC₅₀ values in the DPPH and hydrogen peroxide radical scavenging assays for both flowers and leaves ranged from 18.66 μg/mL to 38.28 μg/mL. Both essential oils also displayed good antibiofilm activities, with the concentration required for half-maximal inhibition of biofilm formation being ∼60 mg/mL for both oils. This study shows that essential oils of Plumeria alba possess good antioxidant and antimicrobial activities and could be used as a source of natural antioxidants and antimicrobial agents.

Old world monkeys separated from the great apes, including the ancestor of humans, about 25 million years ago, but most of the genes in humans and various nonhuman primates are quite similar even though their anatomical appearances are quite different. Like other mammals, primates have four tropomyosin genes (TPM1, TPM2, TPM3, and TPM4) each of which generates a multitude of TPM isoforms via alternative splicing. Only TPM1 produces two sarcomeric isoforms (TPM1α and TPM1κ), and TPM2, TPM3, and TPM4 each generate one sarcomeric isoform. We have cloned and sequenced TPM1α, TPM1κ, TPM2α, TPM3α, and TPM4α with RNA from cynomolgus (Cyn) monkey hearts and skeletal muscle. We believe this is the first report of directly cloning and sequencing of these monkey transcripts. In the Cyn monkey heart, the rank order of TPM isoform expression is TPM1α > TPM2α > TPM1κ > TPM3α > TPM4α. In the Cyn monkey skeletal muscle, the rank order of expression is TPM1α > TPM2α > TPM3α > TPM1κ > TPM4α. The major differences in the human heart are the increased expression of TPM1κ, although TPM1α is still the dominant transcript. In the Cyn monkey heart, the only sarcomeric TPM isoform at the protein level is TPM1α. This is in contrast to human hearts where TPM1α is the major sarcomeric isoform but a lower quantity of TPM1κ, TPM2α, and TPM3α is also detected at the protein level. These differences of tropomyosin and/or other cardiac protein expression in human and Cyn monkey hearts may reflect the differences in physiological activities in daily life.

Background and Objectives. Moringa oleifera has been scientifically reported to have effects on diabetes and obesity. An explanatory mechanism on how the plant exerts its enzyme inhibitory activities are yet to be detailed. This study was aimed at carrying out an in vitro assessment of ethanolic extracts (AEEs) of M. oleifera leaves for their antioxidant, antidiabetic, and antiobesity activities. Methods. Phytochemical screening, antioxidant activity, α-amylase, and α-lipase inhibitory assessment were carried out on Moringa oleifera extract. Results. The result of the phytochemical screening revealed the presence of total phenolic, flavonoid, tannin, and alkaloid contents of values 0.070 ± 0.005 mg gallic acid equivalent/g, 0.180 ± 0.020 mg rutin equivalent/g, 0.042 ± 0.001 mg tannic equivalent/g, and 12.17 ± 0.001%, respectively, while the total protein analysis was 0.475 ± 0.001 mg bovine serum albumin equivalent/g. Ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC) values were 0.534 ± 0.001 mg gallic acid equivalent/g and 0.022 ± 0.00008 mg rutin equivalent/g, respectively. Diphenyl-2-picrylhydrazyl (DPPH), ABTS (2,2′-azino-bis (ethylbenzothiazoline-6-sulfonic acid)), and nitric oxide (NO) assays showed the extract to have a strong free radical scavenging activity. The 50% inhibitory concentration (IC₅₀) values of the lipase and amylase activities of the extract are 1.0877 mg/mL and 0.1802 mg/mL, respectively. Conclusion. However, α-lipase and α-amylase inhibiting activity of M. oleifera could be related to the phytochemicals in the extract. This research validates the ethnobotanical use of M. oleifera leaves as an effective plant-based therapeutic agent for diabetes and obesity.