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The correction notice for the article "ABBV-744 as a potential inhibitor of SARS-CoV-2 main protease enzyme against COVID-19" in Scientific Reports addresses errors in the Introduction section and corrects a reference citation. The correct reference is provided, and it is noted that these changes do not impact the conclusions of the article. The authors of the correction notice are Zeynab Fakhar, Shama Khan, Suliman Y. AlOmar, Afrah Alkhuriji, and Aijaz Ahmad. [Extracted from the article]

Aim: Malaria vaccine is one of the critical areas in tropical health research, considering the success recorded in other vaccine‐preventable diseases. This study is aimed at reviewing recent trends in global malaria vaccine research from 2005 to 2022. Method: A validated search strategy was undertaken to identify scientific literature on the malaria vaccine in the Scopus database. Bibliometric indicators identified include a pattern of publication growth and citations over the study period; top authors, countries, funding organizations, and journals; keywords, including different malarial parasite species, and the overall research themes. Result: A total of 6457 documents were found from 2005 to 2022, published in 160 journals/sources in 189 countries/territories. Malaria Journal published the highest number of research outputs (478, 7.4%) within the study period, and the highest number of documents (468, 7.3%) were published in 2021. There were 214,323 total citations, with 33.2 average citations per document and 167 documents' h‐index. The United States, United Kingdom, and Australia combined produced more than 60% of the publication output, with most collaboration with African countries such as Kenya. Plasmodium falciparum is the most occurring parasite species keyword (754, 11.7%), with a growing interest in Plasmodium knowlesi (30, 0.5%). Merozoite surface protein, characterization, trials, infant/children, traveler, and research/review were the six themes that emerged from the studies. Conclusion: The last one and half decades have seen a significant increase in malaria vaccine research and citations, mainly targeting vaccine development, safety, and efficacy in Africa. This necessitates more international efforts to improve the vaccines' effectiveness considering different Plasmodium species. [ABSTRACT FROM AUTHOR]

Background: Single-domain von Willebrand factor type C (SVWC) constitute a protein family predominantly identified in arthropods, characterized by a SVWC domain and involved in diverse physiological processes such as host defense, stress resistance, and nutrient metabolism. Nevertheless, the physiological mechanisms underlying these functions remain inadequately comprehended. Results: A massive expansion of the SVWC gene family in Musca domestica (MdSVWC) was discovered, with a count of 35. MdSVWC1 was selected as the representative of the SVWC family for functional analysis, which led to the identification of the immune function of MdSVWC1 as a novel pattern recognition receptor. MdSVWC1 is highly expressed in both the fat body and intestines and displays acute induction upon bacterial infection. Recombinant MdSVWC1 binds to surfaces of both bacteria and yeast through the recognition of multiple pathogen-associated molecular patterns and exhibits Ca2+-dependent agglutination activity. MdSVWC1 mutant flies exhibited elevated mortality and hindered bacterial elimination following bacterial infection as a result of reduced hemocyte phagocytic capability and weakened expression of antimicrobial peptide (AMP) genes. In contrast, administration of recombinant MdSVWC1 provided protection to flies from bacterial challenges by promoting phagocytosis and AMP genes expression, thereby preventing bacterial colonization. MdSPN16, a serine protease inhibitor, was identified as a target protein of MdSVWC1. It was postulated that the interaction of MdSVWC1 with MdSPN16 would result in the activation of an extracellular proteolytic cascade, which would then initiate the Toll signaling pathway and facilitate the expression of AMP genes. Conclusions: MdSVWC1 displays activity as a soluble pattern recognition receptor that regulates cellular and humoral immunity by recognizing microbial components and facilitating host defense. [ABSTRACT FROM AUTHOR]

Cephalostatin 1, OSW-1, ritterazine B and schweinfurthin A are natural products that potently, and in some cases selectively, inhibit the growth of cultured human cancer cell lines. The cellular targets of these small molecules have yet to be identified. We have discovered that these molecules target oxysterol binding protein (OSBP) and its closest paralog, OSBP-related protein 4L (ORP4L)--proteins not known to be involved in cancer cell survival. OSBP and the ORPs constitute an evolutionarily conserved protein superfamily, members of which have been implicated in signal transduction, lipid transport and lipid metabolism. The functions of OSBP and the ORPs, however, remain largely enigmatic. Based on our findings, we have named the aforementioned natural products ORPphilins. Here we used ORPphilins to reveal new cellular activities of OSBP. The ORPphilins are powerful probes of OSBP and ORP4L that will be useful in uncovering their cellular functions and their roles in human diseases.

Shikimic acid can be transformed into monovalent and multivalent glycomimetics that target different members of the C-type lectin class, including DC-SIGN, a dendritic cell lectin that facilitates HIV transmission.

A new strategy is presented for the synthesis of graft copolymers using only the ring-opening metathesis polymerization (ROMP). From a ROMP-derived main chain, pendant maleimide functional groups are converted into norbornene moieties via a Diels-Alder reaction with cyclopentadiene. The norbornene groups serve as sites of initiation, and subsequent ROMP from the main chain yields graft copolymers with both main and side chains derived from ROMP. This strategy offers ready access to defined graft copolymers.

This review discusses how research around the oxysterol-binding protein family has evolved. We briefly summarize how this protein family, designated OSBP-related (ORP) or OSBP-like (OSBPL) proteins, was discovered, how protein domains highly conserved among family members between taxa paved the way for understanding their mechanisms of action, and how insights into protein structural and functional features help to understand their versatility as lipid transporters. We also discuss questions and future avenues of research opened by these findings. The investigations on oxysterol-binding protein family serve as a real-life example of the notion that science often advances as a collective effort of multiple lines of enquiry, including serendipitous routes. While original articles invariably explain the motivation of the research undertaken in rational terms, the actual paths to findings may be less intentional. Fortunately, this does not reduce the impact of the discoveries made. Besides hopefully providing a useful account of ORP family proteins, we aim to convey this message. [ABSTRACT FROM AUTHOR]

Mucosal immunity plays a crucial role in defending against coronaviruses, particularly at respiratory sites, serving as the first line of defense against viral invasion and replication. Coronaviruses have developed various immune evasion strategies at the mucosal immune system, hindering the recognition of infected cells and evading antibody responses. Understanding the immune mechanisms and responses is crucial for developing effective vaccines and therapeutics against coronaviruses. The role of mucosal immunity in COVID-19 is significant, influencing both local and systemic immune responses to the virus. Although most clinical studies focus on antibodies and cellular immunity in peripheral blood, mucosal immune responses in the respiratory tract play a key role in the early restriction of viral replication and the clearance of SARS-CoV-2. Identification of mucosal biomarkers associated with viral clearance will allow monitoring of infection-induced immunity. Mucosally delivered vaccines and those under clinical trials are being compared and contrasted to understand their effectiveness in inducing mucosal immunity against coronaviruses. A greater understanding of lung tissue-based immunity may lead to improved diagnostic and prognostic procedures and novel treatment strategies aimed at reducing the disease burden of community-acquired pneumonia, avoiding the systemic manifestations of infection and excess morbidity and mortality. This comprehensive review article outlines the current evidence about the role of mucosal immune responses in the clearance of SARS-CoV-2 infection, as well as potential mucosal mechanisms of protection against (re-)infection. It also proposes that there is a significant role for mucosal immunity and for secretory as well as circulating IgA antibodies in COVID-19, and that it is important to elucidate this in order to comprehend especially the asymptomatic and mild states of the infection, which appear to account for the majority of cases. Moreover, it is possible that mucosal immunity can be exploited for beneficial diagnostic, therapeutic, or prophylactic purposes. The findings from recent studies on mucosal immunity in COVID-19 can be used to develop effective vaccines and treatments that can effectively target both mucosal and systemic immune responses. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Oxysterol-binding protein (OSBP) is known for its crucial role in lipid transport, facilitating cholesterol exchange between the Golgi apparatus and endoplasmic reticulum membranes. Despite its established function in cellular processes, its involvement in coronavirus replication remains unclear. Methods: In this study, we investigated the role of OSBP in coronavirus replication and explored the potential of a novel OSBP-binding compound, ZJ-1, as an antiviral agent against coronaviruses, including SARS-CoV-2. We utilized a combination of biochemical and cellular assays to elucidate the interactions between OSBP and SARS-CoV-2 non-structural proteins (Nsps) and other viral proteins. Results: Our findings demonstrate that OSBP positively regulates coronavirus replication. Moreover, treatment with ZJ-1 resulted in reduced OSBP levels and exhibited potent antiviral effects against multiple coronaviruses. Through our investigation, we identified specific interactions between OSBP and SARS-CoV-2 Nsps, particularly Nsp3, Nsp4, and Nsp6, which are involved in doublemembrane vesicle formation--a crucial step in viral replication. Additionally, we observed that Nsp3 a.a.1-1363, Nsp4, and Nsp6 target vesicle-associated membrane protein (VAMP)-associated protein B (VAP-B), which anchors OSBP to the ER membrane. Interestingly, the interaction between OSBP and VAP-B is disrupted by Nsp3 a.a.1-1363 and partially impaired by Nsp6. Furthermore, we identified SARS-CoV-2 orf7a, orf7b, and orf3a as additional OSBP targets, with OSBP contributing to their stabilization. Conclusion: Our study highlights the significance of OSBP in coronavirus replication and identifies it as a promising target for the development of antiviral therapies against SARS-CoV-2 and other coronaviruses. These findings underscore the potential of OSBP-targeted interventions in combating coronavirus infections. [ABSTRACT FROM AUTHOR]

Human lectins are integral to maintaining microbial homeostasis on the skin, in the blood, and at mucosal barriers. These proteins can recognize microbial glycans and inform the host about its microbial status. In accordance with their roles, their production can vary with tissue type. They also can have unique structural and biochemical properties, and they can influence microbial colonization at sites proximal and distal to their tissue of origin. In line with their classification as innate immune proteins, soluble lectins have long been studied in the context of acute infectious disease, but only recently have we begun to appreciate their roles in maintaining commensal microbial communities (i.e., the human microbiota). This review provides an overview of soluble lectins that operate at host–microbe interfaces, their glycan recognition properties, and their roles in physiological and pathological mechanisms. [ABSTRACT FROM AUTHOR]

Molecular docking has become an essential part of a structural biologist's and medicinal chemist's toolkits. Given a chemical compound and the three-dimensional structure of a molecular target—for example, a protein—docking methods fit the compound into the target, predicting the compound's bound structure and binding energy. Docking can be used to discover novel ligands for a target by screening large virtual compound libraries. Docking can also provide a useful starting point for structure-based ligand optimization or for investigating a ligand's mechanism of action. Advances in computational methods, including both physics-based and machine learning approaches, as well as in complementary experimental techniques, are making docking an even more powerful tool. We review how docking works and how it can drive drug discovery and biological research. We also describe its current limitations and ongoing efforts to overcome them. [ABSTRACT FROM AUTHOR]

The Arctic region's unfavorable living conditions adversely affect the spread of infectious diseases, including COVID-19, This, in turn, can also lead to increased morbidity and mortality rates in the area due to a number of factors such as climate, environment, and high prevalence rate of pre-existing health issues like diabetes, obesity, and respiratory infections. These circumstances adversely affect maintaining the level of working capability. The aim of this paper is to investigate the ratio of immunocompetent cells involved in the adaptive post-COVID-19 immune response. The research includes an immunological assessment of 29 women aged 20-40 years residing in Arkhangelsk, Russia, six months after recovering from COVID-19. The count of leukocytes in the peripheral blood and their differ ential were evaluated using standard methods to assess the immunological status. To delve deeper into the immunological landscape, phenotypes of lymphocytes (CD5+, CD8+, CD10+, and CD95+) were evaluated using an indirect immunoperoxidase reaction with monoclonal antibodies on dried drop lymphocyte preparations. After incubating blood with latex molecules, the activity and quantity of phagocytes were assessed using a light microscope. The neutrophil/lymphocyte ratio was found to be inverted in the female subjects under investigation. The high concentration of cytotoxic T-lymphocytes (CD8+) and lymphocytes with apoptotic receptors (CD95+) suggests a potential correlation with a concurrent reduction in the expression of the total T-cell marker (CD5+) across all cases. This association was further linked to a decrease in lymphoproliferative activity and a relative decline in phagocytic activity. These findings led us to posit that the total recovery time after COVID-19 might extend beyond six months, indicative of a prolonged impact on the body's protective capacity. Our observations prompt the hypothesis that cellular immunity plays a crucial role in determining the severity of COVID-19 infection. Specifically, individuals with initially robust phagocytic activity may be predisposed to experiencing a milder form of the infection. However, this assumption warrants further investigation and clarification in individuals with moderate and severe disease progression [ABSTRACT FROM AUTHOR]

The rapid development of the COVID-19 pandemic resulted in a closer analysis of cell functioning during β-coronavirus infection. This review will describe evidence for COVID-19 as a syndrome with a strong, albeit still underestimated, mitochondrial component. Due to the sensitivity of host mitochondria to coronavirus infection, SARS-CoV-2 affects mitochondrial signaling, modulates the immune response, modifies cellular energy metabolism, induces apoptosis and ageing, worsening COVID-19 symptoms which can sometimes be fatal. Various aberrations across human systems and tissues and their relationships with mitochondria were reported. In this review, particular attention is given to characterization of multiple alterations in gene expression pattern and mitochondrial metabolism in COVID-19; the complexity of interactions between SARS-CoV-2 and mitochondrial proteins is presented. The participation of mitogenome fragments in cell signaling and the occurrence of SARS-CoV-2 subgenomic RNA within membranous compartments, including mitochondria is widely discussed. As SARS-CoV-2 severely affects the quality system of mitochondria, the cellular background for aberrations in mitochondrial dynamics in COVID-19 is additionally characterized. Finally, perspectives on the mitigation of COVID-19 symptoms by affecting mitochondrial biogenesis by numerous compounds and therapeutic treatments are briefly outlined. [ABSTRACT FROM AUTHOR]

In the absence of naturally available galactofuranose-specific lectin, we report herein the bioengineering of GalfNeoLect, from the first cloned wild-type galactofuranosidase (Streptomyces sp. strain JHA19), which recognises and binds a single monosaccharide that is only related to nonmammalian species, usually pathogenic microorganisms. We kinetically characterised the GalfNeoLect to confirm attenuation of hydrolytic activity and used competitive inhibition assay, with close structural analogues of Galf, to show that it conserved interaction with its original substrate. We synthetised the bovine serum albumin-based neoglycoprotein (GalfNGP), carrying the multivalent Galf units, as a suitable ligand and high-avidity system for the recognition of GalfNeoLect which we successfully tested directly with the galactomannan spores of Aspergillus brasiliensis (ATCC 16404). Altogether, our results indicate that GalfNeoLect has the necessary versatility and plasticity to be used in both research and diagnostic lectin-based applications. [ABSTRACT FROM AUTHOR]

Intelectins belong to a family of lectins with specific and transitory carbohydrate interaction capabilities. These interactions are related to the activity of agglutinating pathogens, as intelectins play a significant role in immunity. Despite the prominent immune defense function of intelectins, limited information about its structural characteristics and carbohydrate interaction properties is available. This study investigated an intelectin transcript identified in RNA-seq data obtained from the South American lungfish (Lepidosiren paradoxa), namely LpITLN2-B. The structural analyses predicted LpITLN2-B to be a homo-trimeric globular protein with the fibrinogen-like functional domain (FReD), exhibiting a molecular mass of 57 kDa. The quaternary structure is subdivided into three monomers, A, B, and C, and each domain comprises 11 β-sheets: an anti-parallel β-sheet, a β-hairpin, and a disordered β-sheet structure. Molecular docking demonstrates a significant interaction with disaccharides rather than monosaccharides. The preferential interaction with disaccharides highlights the potential interaction with pathogen molecules, such as LPS and Poly(I:C). The hemagglutination assay inhibited lectins activity, especially maltose and sucrose, highlighting lectin activity in L. paradoxa samples. Overall, our results show the potential relevance of LpITLN2-B in L. paradoxa immune defense against pathogens. [ABSTRACT FROM AUTHOR]

Understanding the antibody response to SARS-CoV-2, the virus responsible for COVID-19, is crucial to comprehending disease progression and the significance of vaccine and therapeutic development. The emergence of highly contagious variants poses a significant challenge to humoral immunity, underscoring the necessity of grasping the intricacies of specific antibodies. This review emphasizes the pivotal role of antibodies in shaping immune responses and their implications for diagnosing, preventing, and treating SARS-CoV-2 infection. It delves into the kinetics and characteristics of the antibody response to SARS-CoV-2 and explores current antibody-based diagnostics, discussing their strengths, clinical utility, and limitations. Furthermore, we underscore the therapeutic potential of SARS-CoV-2-specific antibodies, discussing various antibody-based therapies such as monoclonal antibodies, polyclonal antibodies, anti-cytokines, convalescent plasma, and hyperimmunoglobulin-based therapies. Moreover, we offer insights into antibody responses to SARS-CoV-2 vaccines, emphasizing the significance of neutralizing antibodies in order to confer immunity to SARS-CoV-2, along with emerging variants of concern (VOCs) and circulating Omicron subvariants. We also highlight challenges in the field, such as the risks of antibody-dependent enhancement (ADE) for SARS-CoV-2 antibodies, and shed light on the challenges associated with the original antigenic sin (OAS) effect and long COVID. Overall, this review intends to provide valuable insights, which are crucial to advancing sensitive diagnostic tools, identifying efficient antibody-based therapeutics, and developing effective vaccines to combat the evolving threat of SARS-CoV-2 variants on a global scale. [ABSTRACT FROM AUTHOR]

Human intelectin-1 (hITL-1) has been known to be involved in diseases such as asthma, cancer, metabolic disorders, and inflammatory bowel disease. In the present study, we aimed to evaluate hITL-1 as modulator of metabolic syndrome (MetS) using an in silico approach. AQ2 - The eight selected human (h) proteins, namely tumor necrosis factor-alpha (hTNF-alpha), myeloid differentiation primary response protein 88 (hMyD88), toll like-receptor 4 (hTLR4), cyclooxygenase 2 (hCOX 2), vascular cell adhesion molecule 1 (hVCAM 1), nuclear factor kappa B (hNF kappa B), leptin (hleptin), and interleukin 6 (hIL 6), were investigated on the docking analysis of hITL-1 (protein-protein) by using the HDOCK method. Furthermore, physicochemical properties of eight interested proteins were carried out using ProtParam tool. In the present study, two selected proteins, namely hMyD88, hCOX 2, have shown theoretical isoelectric point (PI) values greater than 7.0 which indicates these proteins are basic in nature. The protein-protein docking analysis showed that hNF kappa B exhibited the maximum docking score of -311.95 (kcal/mol) with the target protein hITL 1. Thus, the present find provides a new knowledge in understanding the hITL 1 as modulator of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background: Intelectin-1 (ITLN1) is an adipokine with multiple physiological functions, including a role in tumour formation and development. Previous research reported variable ITLN1 levels for cancer patients and healthy individuals. This study aimed to compare ITLN1 concentrations between controls and cancer patients and to determine the adipokine's physiological level. Methods: Five databases were searched in January 2022 for studies that measured the level of ITLN1 in adults that were healthy or diagnosed with any type of cancer. After title, abstract and full-text screening, the methodological quality of the studies was assessed. The extracted data were meta-analysed using the R language and Bayesian statistical techniques. Results: Overall, 15 studies compared circulating ITLN1 levels between healthy individuals (n=3424) and cancer patients (n=1538), but no differences were observed between these studies. ITLN1 was not different between groups in an analysis that evaluated high-quality studies only (n=5). The meta-analysis indicated considerably higher ITLN1 levels in gastrointestinal (i.e., colorectal, pancreatic, gastric) cancer compared to controls, while the other cancer types did not demonstrate differences between groups. The mean ITLN1 level of healthy individuals was 234 ± 21ng/ml (n=136), while the average value in high-quality studies (n=52) was 257 ± 31ng/ml. Conclusion: Different types of cancer showed different circulating ITLN1 patterns. Circulating ITLN1 concentration was higher in gastrointestinal cancer compared to controls, with strong support from the meta-analytical model. Our analysis also determined the mean ITLN1 level in healthy individuals; this is a crucial starting point for understanding how this cytokine associates with diseases. Two-thirds of the studies were of low methodological quality and thus, future work in this field must focus on improved methods. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease 19 (COVID-19) has resulted in an estimated 20 million excess deaths and the recent resurgence of COVID-19 in China is predicted to result in up to 1 million deaths over the next few months. With vaccines being ineffective in the case of immunocompromised patients, it is important to continue our quest for safe, effective and affordable drugs that will be available to all countries. Drug repurposing is one of the strategies being explored in this context. Recently, out of the 7817 drugs approved worldwide, 214 candidates were systematically down-selected using a combination of 11 filters including FDA/TGA approval status, assay data against SARS-CoV-2, pharmacokinetic, pharmacodynamic and toxicity profiles. These down-selected drugs were subjected in this study to virtual screening against various SARS-CoV-2 targets followed by molecular dynamics studies of the best scoring ligands against each target. The chosen molecular targets were spike receptor binding domain, nucleocapsid protein RNA binding domain and key nonstructural proteins 3, 5 and 12–14. Four drugs approved for other indications — alendronate, cromolyn, natamycin and treprostinil — look sufficiently promising from our in-silico studies to warrant further in-vitro and in-vivo investigations as appropriate to ascertain their extent of antiviral activities. The pandemic's death toll of more than 6.8 million deaths demand action. With vaccines that are inadequate for the immunocompromised, urgent focus shifts to safe treatment regimen. A rigorous study narrowed 214 repurposed drug candidates, identified alendronate, cromolyn, natamycin and treprostinil through virtual screening which needs to be evaluated in-vitro against COVID-19. [ABSTRACT FROM AUTHOR]

Lactoferrins and lactoferrin-derived peptides display numerous functions linked to innate immunity in mammalians, spanning from antimicrobial to anti-inflammatory and immunomodulatory actions, and even demonstrate antitumor properties. To date, the proposed mechanisms for their biological actions are varied, although the molecular basis that governs lactoferrin interactions with molecular targets has been clarified only in a limited number of specific cases. However, key in silico methods have recently moved the topic to the fore, thus greatly expanding the possibilities of large-scale investigations on macromolecular interactions involving lactoferrins and their molecular targets. This review aims to summarize the current knowledge on the structural determinants that drive lactoferrin recognition of molecular targets, with primary focus on the mechanisms of activity against bacteria and viruses. The understanding of the structural details of lactoferrins' interaction with their molecular partners is in fact a crucial goal for the development of novel pharmaceutical products. [ABSTRACT FROM AUTHOR]

Efforts to develop vaccine and immunotherapeutic countermeasures against the COVID-19 pandemic focus on targeting the trimeric spike (S) proteins of SARS-CoV-2. Vaccines and therapeutic design strategies must impart the characteristics of virion S from historical and emerging variants onto practical constructs such as soluble, stabilized trimers. The virus spike is a heterotrimer of two subunits: S1, which includes the receptor binding domain (RBD) that binds the cell surface receptor ACE2, and S2, which mediates membrane fusion. Previous studies suggest that the antigenic, structural, and functional characteristics of virion S may differ from current soluble surrogates. For example, it was reported that certain anti-glycan, HIV-1 neutralizing monoclonal antibodies bind soluble SARS-CoV-2 S but do not neutralize SARS-CoV-2 virions. In this study, we used single-molecule fluorescence correlation spectroscopy (FCS) under physiologically relevant conditions to examine the reactivity of broadly neutralizing and non-neutralizing anti-S human monoclonal antibodies (mAbs) isolated in 2020. Binding efficiency was assessed by FCS with soluble S trimers, pseudoviruses and inactivated wild-type virions representing variants emerging from 2020 to date. Anti-glycan mAbs were tested and compared. We find that both anti-S specific and anti-glycan mAbs exhibit variable but efficient binding to a range of stabilized, soluble trimers. Across mAbs, the efficiencies of soluble S binding were positively correlated with reactivity against inactivated virions but not pseudoviruses. Binding efficiencies with pseudoviruses were generally lower than with soluble S or inactivated virions. Among neutralizing mAbs, potency did not correlate with binding efficiencies on any target. No neutralizing activity was detected with anti-glycan antibodies. Notably, the virion S released from membranes by detergent treatment gained more efficient reactivity with anti-glycan, HIV-neutralizing antibodies but lost reactivity with all anti-S mAbs. Collectively, the FCS binding data suggest that virion surfaces present appreciable amounts of both functional and nonfunctional trimers, with neutralizing anti-S favoring the former structures and non-neutralizing anti-glycan mAbs binding the latter. S released from solubilized virions represents a nonfunctional structure bound by anti-glycan mAbs, while engineered soluble trimers present a composite structure that is broadly reactive with both mAb types. The detection of disparate antigenicity and immunoreactivity profiles in engineered and virion-associated S highlight the value of single-virus analyses in designing future antiviral strategies against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Copyright of Seikagaku Journal of Japanese Biochemical is the property of Japanese Biochemical Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nanobodies, derived from camelids and sharks, offer compact, single-variable heavy-chain antibodies with diverse biomedical potential. This review explores their generation methods, including display techniques on phages, yeast, or bacteria, and computational methodologies. Integrating experimental and computational approaches enhances understanding of nanobody structure and function. Future trends involve leveraging next-generation sequencing, machine learning, and artificial intelligence for efficient candidate selection and predictive modeling. The convergence of traditional and computational methods promises revolutionary advancements in precision biomedical applications such as targeted drug delivery and diagnostics. Embracing these technologies accelerates nanobody development, driving transformative breakthroughs in biomedicine and paving the way for precision medicine and biomedical innovation., (© 2024 The Author(s). Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

The lipid phosphatidylinositol 4-phosphate (PI4P) plays a master regulatory role at Golgi membranes, orchestrating membrane budding, non-vesicular lipid transport and membrane organization. It follows that harmonious Golgi function requires strictly maintained PI4P homeostasis. One of the most abundant PI4P effector proteins is the oxysterol binding protein (OSBP), a lipid transfer protein that exchanges trans-Golgi PI4P for ER cholesterol. Although this protein consumes PI4P as part of its lipid anti-porter function, whether it actively contributes to Golgi PI4P homeostasis has been questioned. Here, we employed a series of acute and chronic genetic manipulations, together with orthogonal targeting of OSBP, to interrogate its control over Golgi PI4P abundance. Modulating OSBP levels at ER:Golgi membrane contact sites produces reciprocal changes in PI4P levels. Additionally, we observe that OSBP has a high capacity for PI4P turnover, even at orthogonal organelle membranes. However, despite also visiting the plasma membrane, endogenous OSBP makes no impact on PI4P levels in this compartment. We conclude that OSBP is a major determinant of Golgi PI4P homeostasis. [ABSTRACT FROM AUTHOR]

Background: The three-finger proteins are a collection of disulfide bond rich proteins of great biomedical interests. Scalable recombinant expression and purification of bioactive three-finger proteins is quite difficult. Results: We introduce a working pipeline for expression, purification and validation of disulfide-bond rich three-finger proteins using E. coli as the expression host. With this pipeline, we have successfully obtained highly purified and bioactive recombinant α-Βungarotoxin, k-Bungarotoxin, Hannalgesin, Mambalgin-1, α-Cobratoxin, MTα, Slurp1, Pate B etc. Milligrams to hundreds of milligrams of recombinant three finger proteins were obtained within weeks in the lab. The recombinant proteins showed specificity in binding assay and six of them were crystallized and structurally validated using X-ray diffraction protein crystallography. Conclusions: Our pipeline allows refolding and purifying recombinant three finger proteins under optimized conditions and can be scaled up for massive production of three finger proteins. As many three finger proteins have attractive therapeutic or research interests and due to the extremely high quality of the recombinant three finger proteins we obtained, our method provides a competitive alternative to either their native counterparts or chemically synthetic ones and should facilitate related research and applications. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has underscored the need for rapid and cost- effective diagnostic tools. Serological tests, particularly those measuring antibodies targeting the receptor-binding domain (RBD) of the virus, play a pivotal role in tracking infection dynamics and vaccine effectiveness. In this study, we aimed to develop a simple enzyme-linked immunosorbent assay (ELISA) for measuring RBD-specific antibodies, comparing two plant-based platforms for diagnostic reagent production. We chose to retain RBD in the endoplasmic reticulum (ER) to prevent potential immunoreactivity issues associated with plant-specific glycans. We produced ER-retained RBD in two plant systems: a stable transformation of BY-2 plant cell culture (BY2-RBD) and a transient transformation in Nicotiana benthamiana using the MagnICON system (NB-RBD). Both systems demonstrated their suitability, with varying yields and production timelines. The plant-made proteins revealed unexpected differences in N-glycan profiles, with BY2-RBD displaying oligo-mannosidic N-glycans and NB-RBD exhibiting a more complex glycan profile. This difference may be attributed to higher recombinant protein synthesis in the N. benthamiana system, potentially overloading the ER retention signal, causing some proteins to traffic to the Golgi apparatus. When used as diagnostic reagents in ELISA, BY2-RBD outperformed NB-RBD in terms of sensitivity, specificity, and correlation with a commercial kit. This discrepancy may be due to the distinct glycan profiles, as complex glycans on NB-RBD may impact immunoreactivity. In conclusion, our study highlights the potential of plant-based systems for rapid diagnostic reagent production during emergencies. However, transient expression systems, while offering shorter timelines, introduce higher heterogeneity in recombinant protein forms, necessitating careful consideration in serological test development. [ABSTRACT FROM AUTHOR]

The accurate prediction of binding free energy is a major challenge in structure-based drug design. Quantum mechanics (QM)-based approaches show promising potential in predicting ligand–protein binding affinity by accurately describing the behavior and structure of electrons. However, traditional QM calculations face computational limitations, hindering their practical application in drug design. Nevertheless, the fragment molecular orbital (FMO) method has gained widespread application in drug design due to its ability to reduce computational costs and achieve efficient ab initio QM calculations. Although the FMO method has demonstrated its reliability in calculating the gas phase potential energy, the binding of proteins and ligands also involves other contributing energy terms, such as solvent effects, the 'deformation energy' of a ligand's bioactive conformations, and entropy. Particularly in cases involving ionized fragments, the calculation of solvation free energy becomes particularly crucial. We conducted an evaluation of some previously reported implicit solvent methods on the same data set to assess their potential for improving the performance of the FMO method. Herein, we develop a new QM-based binding free energy calculation method called FMOScore, which enhances the performance of the FMO method. The FMOScore method incorporates linear fitting of various terms, including gas-phase potential energy, deformation energy, and solvation free energy. Compared to other widely used traditional prediction methods such as FEP+, MM/PBSA, MM/GBSA, and Autodock vina, FMOScore showed good performance in prediction accuracies. By constructing a retrospective case study, it was observed that incorporating calculations for solvation free energy and deformation energy can further enhance the precision of FMO predictions for binding affinity. Furthermore, using FMOScore-guided lead optimization against Src homology-2-containing protein tyrosine phosphatase 2 (SHP-2), we discovered a novel and potent allosteric SHP-2 inhibitor (compound 8). [ABSTRACT FROM AUTHOR]

The mucus layer covering the skin of fish has several roles, including protection against pathogens and mechanical damage in which proteins play a key role. While proteins in the skin mucus layer of various common bony fish species have been explored, the proteins of shark skin mucus remain unexplored. In this pilot study, we examine the protein composition of the skin mucus in spiny dogfish sharks and chain catsharks through mass spectrometry (NanoLC-MS/MS). Overall, we identified 206 and 72 proteins in spiny dogfish (Squalus acanthias) and chain catsharks (Scyliorhinus retifer), respectively. Categorization showed that the proteins belonged to diverse biological processes and that most proteins were cellular albeit a significant minority were secreted, indicative of mucosal immune roles. The secreted proteins are reviewed in detail with emphasis on their immune potentials. Moreover, STRING protein–protein association network analysis showed that proteins of closely related shark species were more similar as compared to a more distantly related shark and a bony fish, although there were also significant overlaps. This study contributes to the growing field of molecular shark studies and provides a foundation for further research into the functional roles and potential human biomedical implications of shark skin mucus proteins. [ABSTRACT FROM AUTHOR]

Nelumbo nucifera Gaertn., an aquatic medicinal plant (Nelumbonaceae family), has a history of use in traditional medicine across various regions. Our previous study demonstrated the skin anti-aging potential of its stamen ethanolic extract by effectively inhibiting collagenase and tyrosinase enzymes. While the major constituents of this extract are well documented, there is a lack of research on the individual compounds' abilities to inhibit skin aging enzymes. Therefore, this study aimed to evaluate the anti-aging potential of the primary flavonoids found in N. nucifera using both in silico and in vitro approaches. Our initial step involved molecular docking to identify compounds with the potential to inhibit collagenase, elastase, and tyrosinase. Among the seven flavonoids studied, kaempferol-3-O-robinobioside (Kae-3-Rob) emerged as the most promising candidate, exhibiting the highest docking scores for three skin aging-related enzymes. Subsequent enzyme-based inhibition assays confirmed that Kae-3-Rob displayed robust inhibitory activity against collagenase (58.24 ± 8.27%), elastase (26.29 ± 7.16%), and tyrosinase (69.84 ± 6.07%). Furthermore, we conducted extensive 200-ns molecular dynamics (MD) simulations, revealing the stability of the complexes formed between Kae-3-Rob and each enzyme along the MD simulation time. MM/PBSA-based binding free energy calculations indicated the considerably stronger binding affinity of Kae-3-Rob for collagenase and tyrosinase compared to elastase, which was related to the greater percentage of hydrogen bond occupations. These computational findings were consistent with the relatively high inhibitory activity of Kae-3-Rob against collagenase and tyrosinase observed in our in vitro experiment. In conclusion, the results obtained from this comprehensive study suggest that Kae-3-Rob, a key flavonoid from N. nucifera, holds significant potential as a source of bioactive compounds for anti-aging cosmeceutical and other phytopharmaceutical application. [ABSTRACT FROM AUTHOR]

Piperine is a plant-derived promising piperamide candidate isolated from the black pepper (Piper nigrum L.). In the last few years, this natural botanical product and its derivatives have aroused much attention for their comprehensive biological activities, including not only medical but also agricultural bioactivities. In order to achieve sustainable development and improve survival conditions, looking for environmentally friendly pesticides with low toxicity and residue is an extremely urgent challenge. Fortunately, plant-derived pesticides are rising like a shining star, guiding us in the direction of development in pesticidal research. In the present review, the recent progress in the biological activities, mechanisms of action, and structural modifications of piperine and its derivatives from 2020 to 2023 are summarized. The structure-activity relationships were analyzed in order to pave the way for future development and utilization of piperine and its derivatives as potent drugs and pesticides for improving the local economic development. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this work was to rapidly produce in plats two recombinant antigens (RBDw-Fc and RBDo-Fc) containing the receptor binding domain (RBD) of the spike (S) protein from SARS-CoV-2 variants Wuhan and Omicron as fusion proteins to the Fc portion of a murine IgG2a antibody constant region (Fc)., Results: The two recombinant antigens were expressed in Nicotiana benthamiana plants, engineered to avoid the addition of N-linked plant-typical sugars, through vacuum agroinfiltration and showed comparable purification yields (about 35 mg/kg leaf fresh weight)., Conclusions: Their Western blotting and Coomassie staining evidenced the occurrence of major in planta proteolysis in the region between the RBD and Fc, which was particularly evident in RBDw-Fc, the only antigen bearing the HRV 3C cysteine protease recognition site. The two RBD N-linked glycosylation sites showed very homogeneous profiles free from plant-typical sugars, with the most abundant glycoform represented by the complex sugar GlcNAc 4 Man 3 . Both antigens were specifically recognised in Western Blot analysis by the anti-SARS-CoV-2 human neutralizing monoclonal antibody J08-MUT and RBDw-Fc was successfully used in competitive ELISA experiments for binding to the angiotensin-converting enzyme 2 receptor to verify the neutralizing capacity of the serum from vaccinated patients. Both SARS-Cov-2 antigens fused to a murine Fc region were rapidly and functionally produced in plants with potential applications in diagnostics., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Although the COVID-19 pandemic appears to be diminishing, the emergence of SARS-CoV-2 variants represents a threat to humans due to their inherent transmissibility, immunological evasion, virulence, and invulnerability to existing therapies. The COVID-19 pandemic affected more than 500 million people and caused over 6 million deaths. Vaccines are essential, but in circumstances in which vaccination is not accessible or in individuals with compromised immune systems, drugs can provide additional protection. Targeting host signaling pathways is recommended due to their genomic stability and resistance barriers. Moreover, targeting host factors allows us to develop compounds that are effective against different viral variants as well as against newly emerging virus strains. In recent years, the globe has experienced climate change, which may contribute to the emergence and spread of infectious diseases through a variety of factors. Warmer temperatures and changing precipitation patterns can increase the geographic range of disease-carrying vectors, increasing the risk of diseases spreading to new areas. Climate change may also affect vector behavior, leading to a longer breeding season and more breeding sites for disease vectors. Climate change may also disrupt ecosystems, bringing humans closer to wildlife that transmits zoonotic diseases. All the above factors may accelerate the emergence of new viral epidemics. Plant-derived products, which have been used in traditional medicine for treating pathological conditions, offer structurally novel therapeutic compounds, including those with anti-viral activity. In addition, plant-derived bioactive substances might serve as the ideal basis for developing sustainable/efficient/cost-effective anti-viral alternatives. Interest in herbal antiviral products has increased. More than 50% of approved drugs originate from herbal sources. Plant-derived compounds offer diverse structures and bioactive molecules that are candidates for new drug development. Combining these therapies with conventional drugs could improve patient outcomes. Epigenetics modifications in the genome can affect gene expression without altering DNA sequences. Host cells can use epigenetic gene regulation as a mechanism to silence incoming viral DNA molecules, while viruses recruit cellular epitranscriptomic (covalent modifications of RNAs) modifiers to increase the translational efficiency and transcript stability of viral transcripts to enhance viral gene expression and replication. Moreover, viruses manipulate host cells' epigenetic machinery to ensure productive viral infections. Environmental factors, such as natural products, may influence epigenetic modifications. In this review, we explore the potential of plant-derived substances as epigenetic modifiers for broad-spectrum anti-viral activity, reviewing their modulation processes and anti-viral effects on DNA and RNA viruses, as well as addressing future research objectives in this rapidly emerging field. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has spurred intense research efforts to identify effective treatments for SARS-CoV-2. In silico studies have emerged as a powerful tool in the drug discovery process, particularly in the search for drug candidates that interact with various SARS-CoV-2 receptors. These studies involve the use of computer simulations and computational algorithms to predict the potential interaction of drug candidates with target receptors. The primary receptors targeted by drug candidates include the RNA polymerase, main protease, spike protein, ACE2 receptor, and transmembrane protease serine 2 (TMPRSS2). In silico studies have identified several promising drug candidates, including Remdesivir, Favipiravir, Ribavirin, Ivermectin, Lopinavir/Ritonavir, and Camostat Mesylate, among others. The use of in silico studies offers several advantages, including the ability to screen a large number of drug candidates in a relatively short amount of time, thereby reducing the time and cost involved in traditional drug discovery methods. Additionally, in silico studies allow for the prediction of the binding affinity of the drug candidates to target receptors, providing insight into their potential efficacy. This study is aimed at assessing the useful contributions of the application of computational instruments in the discovery of receptors targeted in SARS-CoV-2. It further highlights some identified advantages and limitations of these studies, thereby revealing some complementary experimental validation to ensure the efficacy and safety of identified drug candidates. [ABSTRACT FROM AUTHOR]

The successful development of effective viral vaccines depends on well-known correlates of protection, high immunogenicity, acceptable safety criteria, low reactogenicity, and well-designed immune monitoring and serology. Virus-neutralizing antibodies are often a good correlate of protective immunity, and their serum concentration is a key parameter during the pre-clinical and clinical testing of vaccine candidates. Viruses are inherently infectious and potentially harmful, but we and others developed replication-defective SARS-CoV-2 virus-like-particles (VLPs) as surrogates for infection to quantitate neutralizing antibodies with appropriate target cells using a split enzyme-based approach. Here, we show that SARS-CoV-2 and Epstein–Barr virus (EBV)-derived VLPs associate and fuse with extracellular vesicles in a highly specific manner, mediated by the respective viral fusion proteins and their corresponding host receptors. We highlight the capacity of virus-neutralizing antibodies to interfere with this interaction and demonstrate a potent application using this technology. To overcome the common limitations of most virus neutralization tests, we developed a quick in vitro diagnostic assay based on the fusion of SARS-CoV-2 VLPs with susceptible vesicles to quantitate neutralizing antibodies without the need for infectious viruses or living cells. We validated this method by testing a set of COVID-19 patient serum samples, correlated the results with those of a conventional test, and found good sensitivity and specificity. Furthermore, we demonstrate that this serological assay can be adapted to a human herpesvirus, EBV, and possibly other enveloped viruses. [ABSTRACT FROM AUTHOR]

Understanding the role of 3CLpro protease for SARS-CoV-2 replication and knowing the potential of flavonoid molecules like rutin, myricetin, and baicalein against 3CLpro justify an investigation into their inhibition. This study investigates possible bonds and reactivity descriptors of rutin, myricetin, and baicalein through conformational and electronic properties. Density functional theory was used to determine possible interactions. Analyses were carried out through the molecular electrostatic potential, electron localization function, Fukui function descriptors based on frontier orbitals, and non-covalent interactions. A docking study was performed using a resolution of 1.55 Å for 3CLpro to analyze the interactions of rutin, myricetin, and baicalein. Scores of structures showed that rutin is the best ligand, followed by myricetin and baicalein. Docking studies showed that baicalein and rutin can establish effective interactions with residues of the catalytic dyad (Cys145 and His41), but just rutin forms a hydrogen bond. Myricetin, in turn, could not establish an effective interaction with Cys145. Baicalein interaction arose with active residues such as Arg188, Val186, Gln189, and Gln192. Interactions of rutin and myricetin with Arg188 and Gln189 were also found. A critical interaction was observed only for rutin with the hydroxyls of ring A with His41, and also for Cys145 with rings B and C, which is probably related to the highest score of rutin. [ABSTRACT FROM AUTHOR]

Natural products such as domestic herbal drugs which are easily accessible and cost-effective can be used as a complementary treatment in mild and moderate COVID-19 cases. This study aimed to detect and describe the efficiency of phenolics detected in the galangal–cinnamon mixture in the inhibition of SARS-CoV-2's different protein targets. The potential antiviral effect of galangal–cinnamon aqueous extract (GCAE) against Low Pathogenic HCoV-229E was assessed using cytopathic effect inhibition assay and the crystal violet method. Low Pathogenic HCoV-229E was used as it is safer for in vitro laboratory experimentation and due to the conformation and the binding pockets similarity between HCoV-229E and SARS-CoV-2 MPro. The GCAE showed a significant antiviral effect against HCoV-229E (IC50 15.083 µg/mL). Twelve phenolic compounds were detected in the extract with ellagic, cinnamic, and gallic acids being the major identified phenolic acids, while rutin was the major identified flavonoid glycoside. Quantum-chemical calculations were made to find molecular properties using the DFT/B3LYP method with 6-311++G(2d,2p) basis set. Quantum-chemical values such as EHOMO, ELUMO, energy gap, ionization potential, chemical hardness, softness, and electronegativity values were calculated and discussed. Phenolic compounds detected by HPLC-DAD-UV in the GCAE were docked into the active site of 3 HCoV-229E targets (PDB IDs. 2ZU2, 6U7G, 7VN9, and 6WTT) to find the potential inhibitors that block the Coronavirus infection pathways from quantum and docking data for these compounds. There are good adaptations between the theoretical and experimental results showing that rutin has the highest activity against Low Pathogenic HCoV-229E in the GCAE extract. [ABSTRACT FROM AUTHOR]

Dithiocarbamates (DTCs) are a group of chemicals used primarily as fungicides, although they are exploited for various other applications. DTCs represent one of the oldest classes of broad-spectrum fungicides employed worldwide to control fungal diseases on many crops. Due to their ease of synthesis, low production costs (cheap and readily available starting materials) and a fungicidal activity with a multi-site mode of action, they are still among modern agriculture's most extensively used pesticides. Although the environmental degradation in air, water, and soil is relatively rapid due to photolysis and/or hydrolysis, they are among the most frequently detected pesticides in the European Union (EU), also with a high frequency of maximum residue level (MRL) exceedances. The current review aims to comprehensively survey all aspects of DTCs, including the environmental fate, toxicity and analytical methods for determining parental compounds and degradation products in environmental and food samples. Furthermore, the accumulation of carbamate and dithiocarbamate pesticides in vegetables, fruits, bioindicator organisms and human biological samples, as well as their health effects on humans, are also considered in this study. [ABSTRACT FROM AUTHOR]

Intelectins (ITLNs) are a family of calcium-dependent lectins with carbohydrate-binding capacity, are distributed across various vertebrates, and play an important role in the innate immune response against pathogen infection. The yellow catfish Pelteobagrus fulvidraco (Siluriformes: Bagridae) is an economically important fish in China. The aim of this study was to quantify the gene expression of ITLN in response to pathogen-associated molecular patterns (PAMPs) stimulation. Here, the ITLN gene of P. fulvidraco was characterized and named PfITLN. The full-length cDNA of PfITLN was 1132 bp, including a 5'-untranslated region (UTR) of 140 bp, a 3'-UTR of 110 bp, and an open reading frame (ORF) of 882 bp encoding a polypeptide of 293 amino acids, which contains a signal peptide and two fibrinogen-related domains (FReDs). PfITLN had a molecular weight of 32.39 kDa with a theoretical pI of 5.03. The deduced PfITLN amino acid sequence had 81%, 64%, and 55% homology with Ictalurus furcatus, Danio rerio, and Homo sapiens, respectively. Moreover, the predicted tertiary protein structure of PfITLN was highly similar to that of other animals, and phylogenetic analysis showed that the PfITLN protein was close to those of other Teleostei. Real-time quantitative reverse transcription-PCR (qRT-PCR) analysis showed PfITLN expression in all examined tissues, with the highest abundance seen in the liver, followed by the head kidney, spleen, trunk kidney, and muscle. After PAMP infection with lipopolysaccharide (LPS) and polyriboinosinic polyribocytidylic acid (poly I:C), the expression levels of PfITLN were significantly upregulated at different time points. These results suggested that PfITLN might be involved in innate immunity. [ABSTRACT FROM AUTHOR]

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is an immune checkpoint regulator exclusively expressed on T cells that obstructs the cell's effector functions. Ipilimumab (Yervoy®), a CTLA-4 blocking antibody, emerged as a notable breakthrough in modern cancer treatment, showing upfront clinical benefits in multiple carcinomas. However, the exhilarating cost of checkpoint blockade therapy is discouraging and even utmost prominent in developing countries. Thereby, affordability of cancer care has become a point of emphasis in drug development pipelines. Plant expression system blossomed as a cuttingedge platform for rapid, facile to scale-up, and economical production of recombinant therapeutics. Here, we describe the production of an anti-CTLA-4 2C8 antibody in Nicotiana benthamiana. ELISA and bio-layer interferometry were used to analyze antigen binding and binding kinetics. Anticancer responses in vivo were evaluated using knocked-in mice implanted with syngeneic colon tumor. At 4 days post-infiltration, the antibody was transiently expressed in plants with yields of up to 39.65 ± 8.42 μg/g fresh weight. Plant-produced 2C8 binds to both human and murine CTLA-4, and the plant-produced IgG1 also binds to human FcγRIIIa (V158). In addition, the plant-produced 2C8 monoclonal antibody is as effective as Yervoy® in inhibiting tumor growth in vivo. In conclusion, our study underlines the applicability of plant platform to produce functional therapeutic antibodies with promising potential in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 pandemic has resulted in the introduction of several naïve methods of vaccine development, which have been used to prepare novel viral vectors and mRNA-based vaccines. However, reluctance to receive vaccines owing to the uncertainty regarding their safety is prevalent. Therefore, rigorous safety evaluation of vaccines through preclinical toxicity studies is critical to determine the safety profiles of vaccine candidates. This study aimed to evaluate the toxicity profile of HuVac-19, a subunit vaccine of SARS-CoV-2 utilizing the receptor-binding domain as an antigen, in rats, rabbits, and dogs using single- and repeat-dose study designs. Repeat-dose toxicity studies in rats and rabbits showed transient changes in hematological and serum biochemical parameters in the adjuvant and/or vaccine groups; however, these changes were reversed or potentially reversible after the recovery period. Moreover, temporary reversible changes in absolute and relative organ weights were observed in the prostate of rats and the thymus of rabbits. Gross examination of the injection sites in rats and rabbits treated with the adjuvant- and HuVac-19 showed discoloration and foci, whereas histopathological examination showed granulomatous inflammation, inflammatory cell infiltration, and myofiber degeneration/necrosis. This inflammatory response was local, unassociated with other toxicological changes, and resolved. In a pharmacological safety study, no toxicological or physiological changes associated with HuVac-19 administration were observed. In conclusion, HuVac-19 was not associated with any major systemic adverse effects in the general toxicity and safety pharmacology evaluation, demonstrating that HuVac-19 is a vaccine candidate with sufficient capacity to be used in human clinical trials. [ABSTRACT FROM AUTHOR]

Nanobodies, the smallest functional antibody fragment derived from camelid heavy-chain-only antibodies, have emerged as powerful tools for diverse biomedical applications. In this comprehensive review, we discuss the structural characteristics, functional properties, and computational approaches driving the design and optimisation of synthetic nanobodies. We explore their unique antigen-binding domains, highlighting the critical role of complementarity-determining regions in target recognition and specificity. This review further underscores the advantages of nanobodies over conventional antibodies from a biosynthesis perspective, including their small size, stability, and solubility, which make them ideal candidates for economical antigen capture in diagnostics, therapeutics, and biosensing. We discuss the recent advancements in computational methods for nanobody modelling, epitope prediction, and affinity maturation, shedding light on their intricate antigen-binding mechanisms and conformational dynamics. Finally, we examine a direct example of how computational design strategies were implemented for improving a nanobody-based immunosensor, known as a Quenchbody. Through combining experimental findings and computational insights, this review elucidates the transformative impact of nanobodies in biotechnology and biomedical research, offering a roadmap for future advancements and applications in healthcare and diagnostics., (© 2024 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

SARS-CoV-2 was the pathogen responsible for triggering the global COVID-19 outbreak in 2020. Encouraging advancements have been made in the research and development of vaccines and antiviral drugs. Noticeably, the coronavirus reproduction process relies heavily on the SARS-CoV-2 Main protease (Mpro), which is essential for viral replication. Therefore, this review presents computational drug discovery and screening methods aiming at identifying repurposed medications and potent new compounds from existing databases to effectively combat COVID19 by targeting Mpro. This review can aid in understanding Mpro inhibitors and their potential usefulness. [ABSTRACT FROM AUTHOR]

Objectives: Besides the common symptoms of the coronavirus disease 2019 (COVID-19) including fever, shortness of breath, and cough, a "sudden loss of smell" has recently been added as a diagnostic symptom. The relationship between paranasal sinus computed tomography (PNS CT) and sudden loss of smell in COVID-19 was examined. Materials and Methods: Two groups were selected for the study, the COVID-19 and the control groups. The control group consisted of 40 patients who applied to our clinic with headache and therefore underwent PNS CT. The other group consisted of 40 patients with COVID-19 who were diagnosed with sudden loss of smell with the Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test. Clinical and demographic characteristics, tomography results, and olfactory test scores of patients with COVID-19 loss of smell and control group patients were recorded. The relationship between CT changes in the olfactory cleft and the degree of loss of smell was evaluated. The "Opacification in the olfactory cleft" was accepted as a positive CT finding. Results: Comparison of patients with COVID-19 who had a loss of smell and the control group indicated that a significant difference was observed in terms of CT findings (P =.022). When we evaluated the paranasal CTs obtained from our patients with loss of smell, the CT of 13 patients showed pathological findings (P <.05). As the COVID-19 progressed (pneumonia and respiratory failure), the degree of loss of smell increased (P <.05). A statistically significant relationship was found between the CCCRC score and the presence of PNS CT findings (P =.0012). Conclusion: The PNS CT findings are significant in patients with COVID-19 with a loss of smell and were significantly associated with the degree of loss of smell. In patients with olfactory loss due to COVID-19, PNS CT can help in diagnosis. However, for this imaging to be diagnostic, a larger patient series is needed. [ABSTRACT FROM AUTHOR]

Background: It is necessary to determine the knowledge, attitudes, and practices (KAP) of the coronavirus disease 2019 (COVID-19) epidemic for good management and intervention. Objectives: The current study aimed to evaluate the KAP of the public population regarding COVID-19 in the southeastern region of Iran. Methods: A self-constructed questionnaire based on the literature was developed. The items were asked from the participants via a telephone interview in Zahedan, Iran, during September and October 2020. This study evaluated the association of demographic and socioeconomic information using KAP scales. The data were analyzed using SPSS software (version 20.00). A significance level of 0.05 was considered for the study. Results: A total of 524 participants accepted to have an interview via telephone in the study. About 17% and 10.10% of the participants had poor and excellent knowledge, respectively. Moreover, 72.9% and 66.6% of the respondents had good knowledge and attitude, respectively. The practice was good in 42.4%of the participants. Overall, 73.3% of the subjects had good KAP. Gender had a significant association with attitude toward COVID-19 (X² = 18.85; P < 0.001). Place of living did not have any significant association with all scales and overall KAP. Marital status had a significant association with attitude (X² = 15.89; P = 0.003), practice (X² = 9.60; P = 0.048), and KAP (X² = 18.64; P < 0.001) of COVID-19. Education had a significant association with attitude (X² = 19.58; P = 0.012), practice (X² = 20.26; P < 0.001), and KAP (X² = 28.98; P < 0.001) regarding COVID-19. Occupation had a significant association with knowledge (X² = 26.94; P < 0.001), practice (X² = 15.65; P = 0.017), and KAP (X² = 22.29; P < 0.001) regarding COVID-19. Conclusions: The majority of the participants had great knowledge, a positive state of attitude, and acceptable practice. Although the findings are reasonable, it is recommended that the public should proceed to reinforce knowledge, attitude, and practice regarding COVID-19 [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emerged in 2019 and still requiring treatments with fast clinical translatability. Frequent occurrence of mutations in spike glycoprotein of SARS-CoV-2 led the consideration of an alternative therapeutic target to combat the ongoing pandemic. The main protease (Mpro) is such an attractive drug target due to its importance in maturating several polyproteins during the replication process. In the present study, we used a classification structure–activity relationship (CSAR) model to find substructures that leads to to anti-Mpro activities among 758 non-redundant compounds. A set of 12 fingerprints were used to describe Mpro inhibitors, and the random forest approach was used to build prediction models from 100 distinct data splits. The data set's modelability (MODI index) was found to be robust, with a value of 0.79 above the 0.65 threshold. The accuracy (89%), sensitivity (89%), specificity (73%), and Matthews correlation coefficient (79%) used to calculate the prediction performance, was also found to be statistically robust. An extensive analysis of the top significant descriptors unveiled the significance of methyl side chains, aromatic ring and halogen groups for Mpro inhibition. Finally, the predictive model is made publicly accessible as a web-app named Mpropred in order to allow users to predict the bioactivity of compounds against SARS-CoV-2 Mpro. Later, CMNPD, a marine compound database was screened by our app to predict bioactivity of all the compounds and results revealed significant correlation with their binding affinity to Mpro. Molecular dynamics (MD) simulation and molecular mechanics/Poisson Boltzmann surface area (MM/PBSA) analysis showed improved properties of the complexes. Thus, the knowledge and web-app shown herein can be used to develop more effective and specific inhibitors against the SARS-CoV-2 Mpro. The web-app can be accessed from https://share.streamlit.io/nadimfrds/mpropred/Mpropred_app.py. [ABSTRACT FROM AUTHOR]

Background and Aim: Healthcare workers (HCWs) are considered a high‐risk group for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) exposure, ascribed to the amount of time they spend in health‐care facilities (HCFs). This study aimed to assess HCWs' compliance with Infection Prevention and Control (IPC) procedures and the risk of exposure during the early period of the pandemic in Addis Ababa, Ethiopia. Methods: A descriptive cross‐sectional survey was conducted from June to September 2020. With a response rate of 79.2%, a standardized questionnaire was administered among 247 HCWs, working in eight HCFs. Descriptive and multivariate regression analysis was carried out in STATA version 16. Results: About 22.5% (55) of the HCWs had proper adherence to IPC procedures. Of the total participants, 28.2% (69) had proper use of Personal Protective Equipment (PPE), 40% (98) had proper hand hygiene practices, and 33.1% (81) had frequently cleaned their working environment. HCWs who received training on IPC protocols were four times more likely to follow IPC standards than those with no training (adjusted odds ratio [AOR] = 3.93; 95% confidence interval [CI]: 1.46, 10.58). Besides, HCWs working in treatment centers were four times more likely to follow IPC standards than those working in conventional hospitals (AOR = 3.61; 95% CI:1.63, 8.02). Nurses were four times more likely to have adherence to IPC measures than cleaners and runners (AOR = 4.37; 95% CI: 1.38–13.88). Conclusion: The nature and magnitude of the pandemic did not introduce the required degree of adherence to IPC procedures, per se does not match the level of diligence needed to halt SARS‐CoV‐2 transmission. Our finding suggested that providing periodic training of HCWs with particular emphasis on nonclinical staff is commendable. Furthermore, it is necessary to maintain resilent IPC in HCF through continous follow up and safety drills, to assess the readiness of HFCs' adherance to IPC measures under normal circumstances, which could improve prepardeness for an effective response during epidemics. [ABSTRACT FROM AUTHOR]

The monoclonal antibody (mAb)-based treatment is a highly valued therapy against COVID-19, especially for individuals who may not have strong immune responses to the vaccine. However, with the arrival of the Omicron variant and its evolving subvariants, along with the occurrence of remarkable resistance of these SARS-CoV-2 variants to the neutralizing antibodies, mAbs are facing tough challenges. Future strategies for developing mAbs with improved resistance to viral evasion will involve optimizing the targeting epitopes on SARS-CoV-2, enhancing the affinity and potency of mAbs, exploring the use of non-neutralizing antibodies that bind to conserved epitopes on the S protein, as well as optimizing immunization regimens. These approaches can improve the viability of mAb therapy in the fight against the evolving threat of the coronavirus. [ABSTRACT FROM AUTHOR]