Distribution of influenza A and B antibodies and correlation with ABO/Rh blood grouping

Background: Influenza is a clinically-significant infection with significant number of globally reported annual deaths. The aim of this study was to study the distribution of influenza A and B antibodies in Najran, the Southwest region of Saudi Arabia, and to investigate the correlation between demographic characteristics and influenza virus antibody levels.Methods: Enzyme linked immunosorbent assay was used to detect antibody level of influenza A and B. The correlation with ABO/Rh blood groupings was also examined. The total number of participants was 252. Only twenty-four subjects received the flu vaccine.Results: It was found that 33.7% and 24.1% of unvaccinated subjects were IgG-positive for influenza A and B, respectively. Interestingly, the antibody levels of the unvaccinated participants were higher than the vaccinated group. A significant difference was found between unvaccinated participants with O+ and influenza A and B antibody levels (**p=0.0045). The antibody level was inversely correlated with age in influenza B IgG subjects but not influenza A IgG (r=-0.1379; R squared=0.01900; p=0.0375). Forty-three subjects (17%) were positive for antibodies of both influenza A and B.Conclusions: IgG antibody positivity is greater in cases of influenza type A compared to influenza B. A significant correlation was found in the unvaccinated group between influenza B IgG antibody levels and age, but not influenza A (*p=0.0375). More research is needed to investigate the role of O+ blood group in influenza infections

Blue biotechnology: Computational screening of sarcophyton cembranoid diterpenes for SARS-CoV-2 main protease inhibition

The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as Mpro inhibitors with ΔGbinding \u3c -33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against Mpro than darunavir with ΔGbinding values of -43.8 and -34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2

Targeting the RBD of Omicron Variant (B.1.1.529) with Medicinal Phytocompounds to Abrogate the Binding of Spike Glycoprotein with the hACE2 Using Computational Molecular Search and Simulation Approach

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus continues to inflict chaos globally. The emergence of a novel Omicron variant (B.1.1.529) in South Africa harbors 30 mutations in the spike protein. The variant is distinguished from other variants of concern (VOCs) with an increased (15) number of mutations in the receptor-binding domain (RBD) and suggests higher chances of causing reinfections. Initial reports also claimed that this variant escapes all the neutralizing antibodies, thus demanding a novel strategy against it. Thus, in this study, we performed a computational molecular screening against the RBD of the Omicron (B.1.1.529) variant and assessed the binding affinity of potent drugs against the RBD. The multi-steps screening of the South African Natural Compounds Database (SANCDB) revealed four medicinal compounds as excellent (potential) anti-viral agents against the Omicron variant, namely SANC00944, SANC01032, SANC00992, and SANC00317. The simulation analysis of these compounds in complex with the RBD demonstrated stable dynamics and structural compactness. Moreover, the residual flexibility analysis revealed that the flexibility of three loops required for interaction with hACE2 has been reduced by the binding of these drugs. The post-simulation validation of these compounds such as binding free energy, in silico bioactivity, and dissociation constant prediction validated the anti-viral potency of these compounds. The total binding free energy (TBFE) for the SANC01032–RBD complex was reported to be −46.54 kcal/mol; for the SANC01032–RBD complex, the TBFE was −41.88 kcal/mol; for the SANC00992–RBD complex the TBFE was −29.05 kcal/mol, while for the SANC00317–RBD complex the TBFE was −31.03 kcal/mol. The results showed the inhibition potential of these compounds by targeting the RBD. In conclusion, this study will help in the design and discovery of novel drug therapeutics, which may be used against the emerging Omicron variant of SARS-CoV-2

Applications of phage peptide libraries for epitope discovery and identification of novel anti-virals

Advances in phage display technology revolutionised our understanding of molecular interactions. The aim of using phage display is to screen a peptide library for the identification of rare ligand-bound variants with enhanced specific interaction. One of the most common challenges in dealing with an exhaustive peptide library is the selection of target-unrelated peptides. Here we improved methodical approaches that reduce phage binding to the substrate surrounding the target protein. With this we were able to improve the quality of peptide interactions selected from phage libraries. The main purpose of this study is investigate the range of applications of phage-displayed peptide libraries in the context of identifying peptides that interact with virus proteins and antibodies. Using our refined methods, we were able to select inhibitory peptides to Hepatitis C Virus (HCV) that blockade its entry into the host, along with mapping antigenic determinants of several monoclonal antibodies such as anti non-primate hepacivirus (NPHV) antibodies and human HC33.4 anti-HCV antibody. Epitope mapping proved easier than discovering potent viral therapeutics. However, lead sequences were identified that neutralise HCV entry in in vitro models. The presence of thousands of HCV quasispecies leads to another difficulty of discovering pangenotypic inhibitors. Robust alignment and significant binding were demonstrated with peptides selected with both NPHV and HC33.4 human antibodies, while the selection failed with other target proteins. There might be no hot spot residues presented in the libraries used against these proteins. Future investigations should focus on developing the suggested HCV-selected peptides to enhance their affinity. All in all, phage display technology has been successfully developed to improve the performance of peptide libraries in a way that can avoid undesirable sequences during library sorting and enhancing the chance to find favourable ligands

Applications of phage peptide libraries for epitope discovery and identification of novel anti-virals

Advances in phage display technology revolutionised our understanding of molecular interactions. The aim of using phage display is to screen a peptide library for the identification of rare ligand-bound variants with enhanced specific interaction. One of the most common challenges in dealing with an exhaustive peptide library is the selection of target-unrelated peptides. Here we improved methodical approaches that reduce phage binding to the substrate surrounding the target protein. With this we were able to improve the quality of peptide interactions selected from phage libraries. The main purpose of this study is investigate the range of applications of phage-displayed peptide libraries in the context of identifying peptides that interact with virus proteins and antibodies. Using our refined methods, we were able to select inhibitory peptides to Hepatitis C Virus (HCV) that blockade its entry into the host, along with mapping antigenic determinants of several monoclonal antibodies such as anti non-primate hepacivirus (NPHV) antibodies and human HC33.4 anti-HCV antibody. Epitope mapping proved easier than discovering potent viral therapeutics. However, lead sequences were identified that neutralise HCV entry in in vitro models. The presence of thousands of HCV quasispecies leads to another difficulty of discovering pangenotypic inhibitors. Robust alignment and significant binding were demonstrated with peptides selected with both NPHV and HC33.4 human antibodies, while the selection failed with other target proteins. There might be no hot spot residues presented in the libraries used against these proteins. Future investigations should focus on developing the suggested HCV-selected peptides to enhance their affinity. All in all, phage display technology has been successfully developed to improve the performance of peptide libraries in a way that can avoid undesirable sequences during library sorting and enhancing the chance to find favourable ligands

Studying the effect of particulate matter as SARS-CoV-2 transmitters

Background: Studies of risk factors are especially valuable at this difficult time in the midst of a pandemic. High levels of particulate matter (PM) represent a serious risk factor on health. While this is a direct impact on health, indirect effects are worth considering too. Design and Methods: The aim of this study was to investigate the role of PM in the transmission of viruses, especially SARS-CoV-2. Also, we sought to understand dynamics of PM in still air at high and low altitudes. Historic AQI and physical PM measurements were collected between August and September 2020 using air quality detector. Potential correlations between the number of total confirmed COVID-19 cases and average air quality index (AQI) from varied geographic locations were also assessed. Results: Airborne PM levels were weakly associated with COVID-19 cases after analysing 77 territories. PM remained longer in the air at high altitudes compared to measurements made at sea level. This suggests that the link between PM and COVID-19 transmission could be aggravated in areas of high altitude. Conclusions: This article highlights that particulate matter can be involved in SARS-CoV-2 transmission. However, confounding factors may have impacted the association between the two variables. These findings can serve as a foundation for future studies on the effect of air pollutants and fine particulate matter on viral transmission

Non-ionic detergents facilitate non-specific binding of M13 bacteriophage to polystyrene surfaces

© 2015 Elsevier B.V. Phage-displayed random peptide libraries are widely used for identifying peptide interactions with proteins and other substrates. Selection of peptide ligands involves iterative rounds of affinity enrichment. The binding properties of the selected phage clones are routinely tested using immunoassay after propagation to high titre in a bacterial host and precipitation using polyethylene glycol (PEG) and high salt concentration. These immunoassays can suffer from low sensitivity and high background signals. Polysorbate 20 (Tween® 20) is a non-ionic detergent commonly used in immunoassay washing buffers to reduce non-specific binding, and is also used as a blocking reagent. We have observed that Tween 20 enhances non-specific M13 library phage binding in a peptide-independent manner. Other non-ionic detergents were also found to promote significant, dose-dependent non-specific phage binding in ELISA. This effect was not observed for assays using phage concentrated by ultracentrifugation, suggesting that interactions occur between detergents and the PEG-precipitated phage, irrespective of the displayed peptide motif. This artefact may impact on successful affinity selection of peptides from phage-display libraries. We propose alternative methods for screening phage libraries for identifying binding interactions with target ligands

Nanomaterials-Based Novel Immune Strategies in Clinical Translation for Cancer Therapy

Immunotherapy shows a lot of promise for addressing the problems with traditional cancer treatments. Researchers and clinicians are working to create innovative immunological techniques for cancer detection and treatment that are more selective and have lower toxicity. An emerging field in cancer therapy, immunomodulation offers patients an alternate approach to treating cancer. These therapies use the host’s natural defensive systems to identify and remove malignant cells in a targeted manner. Cancer treatment is now undergoing somewhat of a revolution due to recent developments in nanotechnology. Diverse nanomaterials (NMs) have been employed to overcome the limits of conventional anti-cancer treatments such as cytotoxic, surgery, radiation, and chemotherapy. Aside from that, NMs could interact with live cells and influence immune responses. In contrast, unexpected adverse effects such as necrosis, hypersensitivity, and inflammation might result from the immune system (IS)’s interaction with NMs. Therefore, to ensure the efficacy of immunomodulatory nanomaterials, it is essential to have a comprehensive understanding of the intricate interplay that exists between the IS and NMs. This review intends to present an overview of the current achievements, challenges, and improvements in using immunomodulatory nanomaterials (iNMs) for cancer therapy, with an emphasis on elucidating the mechanisms involved in the interaction between NMs and the immune system of the host

Nanomaterials-Based Novel Immune Strategies in Clinical Translation for Cancer Therapy

Immunotherapy shows a lot of promise for addressing the problems with traditional cancer treatments. Researchers and clinicians are working to create innovative immunological techniques for cancer detection and treatment that are more selective and have lower toxicity. An emerging field in cancer therapy, immunomodulation offers patients an alternate approach to treating cancer. These therapies use the host’s natural defensive systems to identify and remove malignant cells in a targeted manner. Cancer treatment is now undergoing somewhat of a revolution due to recent developments in nanotechnology. Diverse nanomaterials (NMs) have been employed to overcome the limits of conventional anti-cancer treatments such as cytotoxic, surgery, radiation, and chemotherapy. Aside from that, NMs could interact with live cells and influence immune responses. In contrast, unexpected adverse effects such as necrosis, hypersensitivity, and inflammation might result from the immune system (IS)’s interaction with NMs. Therefore, to ensure the efficacy of immunomodulatory nanomaterials, it is essential to have a comprehensive understanding of the intricate interplay that exists between the IS and NMs. This review intends to present an overview of the current achievements, challenges, and improvements in using immunomodulatory nanomaterials (iNMs) for cancer therapy, with an emphasis on elucidating the mechanisms involved in the interaction between NMs and the immune system of the host

Development and In Vitro Characterization of Antibiotic-Loaded Nanocarriers for Dental Delivery

The aim of this research work was to formulate and evaluate ciprofloxacin hydrochloride-loaded nanocarriers for treating dental infections and bone regeneration. Periodontal infection is associated with inflammation, soft tissue destruction, and bone loss. The objective of the study was to extract β tricalcium phosphate (β-TCP) from coral beach sand using the hydrothermal conversion method and load these nanocarriers with ciprofloxacin hydrochloride. The developed drug-loaded nanocarriers were evaluated for various parameters. In vitro drug-loading studies showed the highest drug loading of 71% for F1 with a drug: carrier ratio compared to plain ciprofloxacin hydrochloride gel. β-TCP and nanocarriers were evaluated for powder characteristics and the results were found to have excellent and fair flowability. In vitro drug release studies conducted over a period of 5 days confirmed the percentage drug release of 96% at the end of 120 h. Nanocarriers were found to be effective against S. aureus and E. coli showing statistically significant antibacterial activity at (* p < 0.05) significant level as compared to plain ciprofloxacin hydrochloride gel. The particle size of β-TCP and nanocarriers was found to be 2 µm. Fourier transform infra-red studies showed good compatibility between the drug and the excipients. Differential scanning calorimetry studies revealed the amorphous nature of the nanocarriers as evident from the peak shift. It is obvious from the XRD studies that the phase intensity was reduced, which demonstrates a decrease in crystallinity. Nanocarriers released the drug in a controlled manner, hence may prove to be a better option to treat dental caries as compared to conventional treatments