Current Pharmaceutical Biotechnology - Volume 22, Issue 7, 2021

In recent years, extensive attention has been given to the generation of new classes of ligand- specific binding proteins to supplement monoclonal antibodies. A combination of protein engineering and display technologies has been used to manipulate non-human antibodies for humanization and stabilization purposes or even the generation of new binding proteins. Engineered protein scaffolds can now be directed against therapeutic targets to treat cancer and immunological disorders. Although very few of these scaffolds have successfully passed clinical trials, their remarkable properties such as robust folding, high solubility, and small size motivate their employment as a tool for biology and applied science studies. Here, we have focused on the generation of new non-Ig binding proteins and single domain antibody manipulation, with a glimpse of their applications.

Background: The oral application of drugs is the most popular route through which the systemic effect can be achieved. Nevertheless, oral administration is limited by difficulties related to the physicochemical properties of the drug molecule, including low aqueous solubility, instability, low permeability, and rapid metabolism, all of which result in low and irregular oral bioavailability. Objective: The enhancement of oral bioavailability of drug molecules with such properties could lead to extreme complications in drug preparations. Oral lipid-based nanoparticles seem to possess extensive advantages due to their ability to increase the solubility, simplifying intestinal absorption and decrease or eradicate the effect of food on the absorption of low soluble, lipophilic drugs and therefore improving the oral bioavailability. Methods: The present review provides a summary of the general theory of lipid-based nanoparticles, their preparation methods, as well as their oral applications. Moreover, oral drug delivery challenges are discussed. Results: According to this review, the most frequent types of lipid-based nanoparticle, the solid lipid nanoparticles and nanostructured lipid carriers are potent oral carriers due to their ability to penetrate the oral drug adsorption barriers. Moreover, such lipid nanoparticles can be beneficial drug carriers against cardiovascular risk disorders as diabetes, hypertension, etc. Conclusion: In this review, the most current and promising studies involving Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as oral drug carriers are reported aiming to assist researchers who focus their research on lipid-based nanoparticles.

SARS-CoV 2 is a novel virus strain of Coronavirus, reported in China in late December 2019. Its highly contagious nature in humans has prompted WHO to designate the ongoing pandemic as a Public Health Emergency of International Concern. At this moment, there is no specific treatment and the therapeutic strategies to deal with the infection are only supportive, with prevention aimed at reducing community transmission. A permanent solution for the pandemic, which has brought the world economy to the edge of collapse, is the need of the hour. This situation has brought intense research in traditional systems of medicine. Indian Traditional System, Ayurveda, has a clear concept of the cause and treatment of pandemics. Through this review, information on the potential antiviral traditional medicines along with their immunomodulatory pathways are discussed. We have covered the seven most important Indian traditional plants with antiviral properties: Withania somnifera (L.) Dunal (family: Solanaceae), Tinospora cordifolia (Thunb.) Miers (family: Menispermaceae), Phyllanthus emblica L. (family: Euphorbiaceae), Asparagus racemosus L. (family: Liliaceae), Glycyrrhiza glabra L. (family: Fabaceae), Ocimum sanctum L. (family: Lamiaceae) and Azadirachta indica A. Juss (family: Meliaceae) in this review. An attempt is also made to bring into limelight the importance of dietary polyphenol, Quercetin, which is a potential drug candidate in the making against the SARS-CoV2 virus.

Background: The treatment of infection caused by pathogenic bacteria becomes one of the serious concerns globally. The failure in the treatment was found due to the exhibition of multiple resistance mechanisms against the antimicrobial agents. The emergence of resistant bacterial species has also been observed due to prolong treatment using conventional antibiotics. To combat these problems, several alternative strategies have been employed using biological and chemically synthesized compounds as antibacterial agents. Marine organisms are considered as one of the potential sources for the isolation of bioactive compounds due to the easily available, cost-effective, and eco-friendly. Methods: The online search methodology was adapted for the collection of information related to the antimicrobial properties of marine-derived compounds. These compound has been isolated and purified by different purification techniques, and their structure also characterized. Furthermore, the antibacterial activities have been reported by using broth microdilution as well as disc diffusion assays. Results: The present review paper describes the antimicrobial effect of diverse secondary metabolites which are isolated and purified from the different marine organisms. The structural elucidation of each secondary metabolite has also been done in the present paper, which will help for the in silico designing of the novel and potent antimicrobial compounds. Conclusion: A thorough literature search has been made and summarizes the list of antimicrobial compounds that are isolated from both prokaryotic and eukaryotic marine organisms. The information obtained from the present paper will be helpful for the application of marine compounds as antimicrobial agents against different antibiotic-resistant human pathogenic bacteria.

Background: Helicobacter pylori causes dangerous and deadly diseases such as gastric cancer and duodenal ulcers. Eradication and treatment of this bacterium are very important due to the deadly diseases caused by H. pylori and the high cost of treatment for countries. Methods: Thus, we present a complete list of the most important causes of failure in the treatment and eradication of H. pylori, and address new therapeutic methods that may be effective in controlling this bacterium in the future. Results: Many efforts have been made to control and eradicate this bacterium over the years, but no success has been achieved since its eradication is a complex process affected by the bacterial properties and host factors. Previous studies have shown that various factors are involved in the failure to eradicate H. pylori, such as new genotypes of the bacterium with higher pathogenicity, inappropriate patient cooperation, mutations, biofilm formation and dormant forms that cause antibiotic resistance, acidic stomach pH, high bacterial load, smoking, immunosuppressive features and intracellular occurrence of H. pylori. On the other hand, recent studies reported that the use of probiotics, nanoparticles, antimicrobial peptides, natural product and vaccines can be helpful in the treatment and eradication of H. pylori infections. Conclusion: Eradication of H. pylori is crucial for the treatment of important diseases such as gastric cancer. Therefore, it seems that identifying the failure causes of treating this bacterium can be helpful in controlling the infections. Besides, further studies on new therapeutic strategies may help eradicate H. pylori in the future.

Human Immunodeficiency Virus (HIV)-infected persons are at a higher risk of developing Tuberculous Meningitis (TBM). We aimed to estimate the prevalence of TBM-HIV co-infection. We systematically searched Pubmed/Medline, Embase and Cochrane library databases from January 1, 2000, to January 31, 2017, to find relevant studies. We employed the random-effects meta-analysis model to estimate the pooled prevalence of TBM-HIV co-infection. Twenty-six eligible studies showed the prevalence of HIV in TBM patients. In the pooled analyses, the prevalence of HIV was 30% (95% CI: 12-47) in patients with confirmed TBM, and 12.1% (95% CI: 7.3-19.2) in patients with suspected TBM. This study shows a high prevalence of TBM-HIV co-infection. Establishing proper diagnostic criteria and preventive measures for TBM infections could assist in the prevention and management of TBM infection, particularly TBM-HIV co-infection.

Background: Recombinant Keratinocyte Growth Factor (rHuKGF) is a therapeutic protein used widely in oral mucositis after chemotherapy in various cancers, stimulating lung morphogenesis and gastrointestinal tract cell proliferation. In this research study, chitosan-rHuKGF polymeric complex was implemented to improve the stability of rHuKGF and used as rejuvenation therapy for the treatment of oral mucositis in cancer patients. Objective: Complexation of rHuKGF with mucoadhesive low molecular weight chitosan to protect rHuKGF from proteolysis and investigate the effect of chitosan-rHuKGF complex on the proliferation rate of FHs 74 Int cells. Methods: The interaction between chitosan and rHuKGF was studied by molecular docking. Malvern ZetaSizer Nano Zs and Fourier-Transform Infrared spectroscopy (FTIR) tests were carried out to characterize the chitosan-rHuKGF complex. In addition, SDS-PAGE was performed to investigate the interaction between chitosan-rHuKGF complex and pepsin. The effect of chitosan-rHuKGF complex on the proliferation rate of FHs 74 Int cells was studied by MTT assay. Results: Chitosan-rHuKGF complex was formed through the hydrogen bonding proven by the docking studies. A stable chitosan-rHuKGF complex was formed at pH 4.5 and was protected from proteolysis and assessed by SDS PAGE. According to the MTT assay results, chitosan-rHuKGF complex increased the cell proliferation rate of FHs 74 Int cells. Conclusion: The developed complex improved the stability and the biological function of rHuKGF.

Background: The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. Objective: The effect of combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. Methods: Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. Results: All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. Higher activity was correlated to the presence of flavors and nicotine. Discussion: In most cases, the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to the presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. Conclusion: Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.

Background: ZUFSP (Zinc-finger and UFSP domain protein) is a novel representative member of the recently characterized seventh class of deubiquitinating enzymes (DUBs). Due to the roles DUBs play in genetic instability, they have become a major drug target in cancer and neurodegenerative diseases. ZUFSP, being a DUB enzyme has also been implicated in genetic stability. However, no lead compound has been developed to target ZUFSP. Objective/Methods: Therefore, in this study, we used a combined drug repurposing, virtual screening and per-Residue Energy Decomposition (PRED) to identify ZUFSP inhibitors with therapeutic potential. 3-bromo-6-{[4-hydroxy-1-3(3-phenylbutanoyl)piperidin-4-yl]methyl}-4H,5H,6H,7H-thieno[2,3- C]pyridine-7-one (BHPTP) which is an inhibitor of USP7 was repurposed to target ZUFSP. The rationale behind this is based on the similarity of the active between USP7 and ZUFSP. Results: PRED of the binding between BHPTP and ZUFSP revealed Cys223, Arg408, Met410, Asn460, and Tyr465 as the crucial residues responsible for this interaction. The pharmacophoric moieties of BHPTP responsible for this binding along with other physiochemical properties were used as a filter to retrieve potential ligands. 799 compounds were retrieved, ZINC083241427, ZINC063648749, and ZINC063648753 were selected due to the binding energy they exhibited. Cheminformatics analysis revealed that the compounds possess high membrane permeability, however, BHPTP had a low membrane permeability. Furthermore, the compounds are drug like, having obeyed Lipinski’s rule of five. Conclusion: Taken together, findings from this study put ZINC083241427, ZINC063648749, and ZINC063648753 as potential ZUFSP inhibitor, however, more experimental validation is required to unravel the mechanism of actions of these compounds.

Background: Curcumin was found to accelerate gastric ulcer healing by the main mechanism, i.e., the suppression of iNOS mediated inflammation. Although Tetrahydrocurcumin (THC) is claimed to be an active antioxidant element of curcumin, its antiulcer activity has not been systematically examined. The utility of Self-Microemulsifying Drug Delivery Systems (SMEDDSs) for curcumin and THC formulations in the liquid form was also found to increase the rate and extent of release of curcumin- and THC-SMEDDS. Nevertheless, the beneficial antiulcer effect of these nanoproducts has not yet been evaluated. Objective: This study aimed to evaluate and compare the antiulcer efficacy of curcumin- and THCSMEDDS through the inhibition of the iNOS/NO system in the rat model. Methods: Antiulcer efficacy was compared in terms of the ability to accelerate healing of gastric ulcer including the efficient inhibitory action on inflammatory NO production in activated macrophages and iNOS mRNA expression at the ulcerated area. Results: THC was found to have less ulcer healing capacity than curcumin with a lack of significant inhibitory effect on the iNOS/NO system. The SMEDDS used in the study significantly increased the inhibitory efficacy of THC on iNOS/NO production and iNOS mRNA expression compared to the inhibitory potency of curcumin. An oral administration of curcumin- or THC-SMEDDS once a day was appropriate for exerting a comparable curative efficacy to a twice-daily oral administration of curcumin or THC. Conclusion: The SMEDDS used in the study was observed to enhance the inhibitory efficacy of the antiulcer drug on the iNOS/NO system, leading to a reduction of daily dosing and dosing frequency.