Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped positive stranded RNA virus which has caused the recent deadly pandemic called COVID-19. The SARS-CoV-2 virion is coated ...with a heavily glycosylated Spike glycoprotein which is responsible for attachment and entry into target cells. One, as yet unexploited strategy for preventing SARS-CoV-2 infections, is the targeting of the glycans on Spike. Lectins are carbohydrate-binding proteins produced by plants, algae, and cyanobacteria. Some lectins can neutralize enveloped viruses displaying external glycoproteins, offering an alternative therapeutic approach for the prevention of infection with virulent β-coronaviruses, such as SARS-CoV-2. Here we show that the cyanobacterial lectin cyanovirin-N (CV-N) can selectively target SARS-CoV-2 Spike oligosaccharides and inhibit SARS-CoV-2 infection in vitro and in vivo. CV-N neutralizes Delta and Omicron variants in vitro better than earlier circulating viral variants. CV-N binds selectively to Spike with a Kd as low as 15 nM and a stoichiometry of 2 CV-N: 1 Spike but does not bind to the receptor binding domain (RBD). Further mapping of CV-N binding sites on Spike shows that select high-mannose oligosaccharides in the S1 domain of Spike are targeted by CV-N. CV-N also reduced viral loads in the nares and lungs in vivo to protect hamsters against a lethal viral challenge. In summary, we present an anti-coronavirus agent that works by an unexploited mechanism and prevents infection by a broad range of SARS-CoV-2 strains.
Dengue virus (DENV) is the most widespread arbovirus, responsible for a wide range of clinical manifestations, varying from self-limited illness to severe hemorrhagic fever. Dengue severity is ...associated with host intense proinflammatory response and monocytes have been considered one of the key cell types involved in the early steps of DENV infection and immunopathogenesis. To better understand cellular mechanisms involved in monocyte infection by DENV, we analyzed the expression levels of 754 human microRNAs in DENV-infected THP-1 cells, a human monocytic cell line. Eleven human microRNAs showed differential expression after DENV infection and gene ontology and enrichment analysis revealed biological processes potentially affected by these molecules. Five downregulated microRNAs were significantly linked to cellular response to stress, four to cell death/apoptosis, two to innate immune responses and one upregulated to vesicle mediated, TGF-β signaling, phosphatidylinositol mediated signaling, lipid metabolism process and blood coagulation.
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been proven to be an effective means of decreasing COVID-19 mortality, hospitalization rates, and transmission. One ...of the vaccines deployed worldwide is ChAdOx1 nCoV-19, which uses an adenovirus vector to drive the expression of the original SARS-CoV-2 spike on the surface of transduced cells. Using cryo-electron tomography and subtomogram averaging, we determined the native structures of the vaccine product expressed on cell surfaces in situ. We show that ChAdOx1-vectored vaccines expressing the Beta SARS-CoV-2 variant produce abundant native prefusion spikes predominantly in one-RBD-up conformation. Furthermore, the ChAdOx1-vectored HexaPro-stabilized spike yields higher cell surface expression, enhanced RBD exposure, and reduced shedding of S1 compared to the wild type. We demonstrate in situ structure determination as a powerful means for studying antigen design options in future vaccine development against emerging novel SARS-CoV-2 variants and broadly against other infectious viruses.
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•Subtomogram averaging of ChAdOx1 nCoV-19 spikes in situ at subnanometer resolution•HexaPro stabilizes the one-RBD-up prefusion spike conformation•In situ cryo-ET structure of antigens provides rationale for vaccine optimization
Virology; Cell biology
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Glioblastoma is the most frequent and aggressive primary brain cancer. In preclinical studies, Zika virus, a flavivirus that triggers the death of glioblastoma stem-like cells. However, the ...flavivirus oncolytic activity has not been demonstrated in human patients. Here we report a glioblastoma patient who received the standard of care therapy, including surgical resection, radiotherapy and temozolomide. However, shortly after the tumor mass resection, the patient was clinically diagnosed with a typical arbovirus-like infection, during a Zika virus outbreak in Brazil. Following the infection resolution, the glioblastoma regressed, and no recurrence was observed. This clinical response continues 6 years after the glioblastoma initial diagnosis.
Retroviruses have a very complex and tightly controlled life cycle which has been studied intensely for decades. After a virus enters the cell, it reverse-transcribes its genome, which is then ...integrated into the host genome, and subsequently all structural and regulatory proteins are transcribed and translated. The proteins, along with the viral genome, assemble into a new virion, which buds off the host cell and matures into a newly infectious virion. If any one of these steps are faulty, the virus cannot produce infectious viral progeny. Recent advances in structural and molecular techniques have made it possible to better understand this class of viruses, including details about how they regulate and coordinate the different steps of the virus life cycle. In this review we summarize the molecular analysis of the assembly and maturation steps of the life cycle by providing an overview on structural and biochemical studies to understand these processes. We also outline the differences between various retrovirus families with regards to these processes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The Retrovirus Capsid Core Zhang, Wei; Mendonça, Luiza M; Mansky, Louis M
Sub-cellular biochemistry,
01/2018, Volume:
88
Journal Article
Peer reviewed
The retrovirus capsid core is a metastable structure that disassembles during the early phase of viral infection after membrane fusion. The core is intact and permeable to essential nucleotides ...during reverse transcription, but it undergoes disassembly for nuclear entry and genome integration. Increasing or decreasing the stability of the capsid core has a substantial negative impact on virus infectivity, which makes the core an attractive anti-viral target. The retrovirus capsid core also encounters a variety of virus- and organism-specific host cellular factors that promote or restrict viral replication. This review describes the structural elements fundamental to the formation and stability of the capsid core. The physical and chemical properties of the capsid core that are critical to its functional role in reverse transcription and interaction with host cellular factors are highlighted to emphasize areas of current research.
Abstract Pteris congesta an endemic and endangered species was investigated to identify morphological differences between its sterile and fertile leaves. Our findings have unveiled, leaf dimorphism ...in both morphology and growth patterns between fertile and sterile leaves. The sterile leaves petioles exhibited equivalent growth to the laminae, achieving complete leaf expansion within a month. In contrast, the petioles of fertile leaves elongated more than twice the size of the leaf blades that remain closed for the initial 30 days. Spore germination was carried out in both sterile and non-sterile soils, and juvenile sporophytes were cultivated to allow for morphological comparisons with those collected from the wild. One month after sowing the spores germinated in both soils resulting in a uniseriate germ filament Vittaria-type, and differentiated into laminar gametophytes, forming a Ceratopteris-type prothallus. The first leaf of the sporophyte emerged two months after sowing, and its development was completed one month later. Based on our studies, we propose that seedlings cultivated from spores germinated in soil can be used for the reintroduction of endangered fern species.
Resumo Pteris congesta, uma espécie endêmica e ameaçada de extinção, foi investigada para identificar diferenças morfológicas entre suas folhas estéreis e férteis. Revelamos que há dimorfismo foliar tanto morfológico como também nos padrões de crescimento entre as folhas férteis e estéreis. Os pecíolos das folhas estéreis crescem de forma equivalente às lâminas e alcançam a expansão foliar completa em um mês. Em contraste, as folhas férteis alongam mais que o dobro do tamanho das lâminas foliares e permanecem fechadas nos primeiros 30 dias. A germinação de esporos foi realizada em solos estéreis e não estéreis, e esporófitos juvenis foram cultivados para permitir comparações morfológicas com aqueles coletados na natureza. Um mês após a semeadura, os esporos germinaram em ambos os solos resultando em filamentos germinativos unisseriados do tipo Vittaria que se diferenciaram em gametófitos laminares, formando um prótalo do tipo Ceratopteris. A primeira folha do esporófito emergiu dois meses após a semeadura, e seu desenvolvimento foi concluído um mês depois. Com base em nossos estudos, propomos que mudas cultivadas a partir de esporos germinados no solo possam ser utilizadas para a reintrodução de espécies de samambaias ameaçadas de extinção.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Gestational diabetes mellitus (GDM) is characterized by a set of metabolic complications arising from adaptive failures to the pregnancy period. Estimates point to a prevalence of 3 to 15% of ...pregnancies. Its etiology includes intrinsic and extrinsic aspects of the progenitress, which may contribute to the pathophysiogenesis of GDM. Recently, researchers have identified that inflammation, oxidative stress, and the gut microbiota participate in the development of the disease, with potentially harmful effects on the health of the maternal-fetal binomial, in the short and long terms. In this context, alternative therapies were investigated from two perspectives: the modulation of the intestinal microbiota, with probiotics and prebiotics, and the use of natural products with antioxidant and anti-inflammatory properties, which may mitigate the endogenous processes of the GDM, favoring the health of the mother and her offspring, and in a future perspective, alleviating this critical public health problem.
Abstract The impact of herbal salt as a natural antioxidant on the lipids of roasted Dolphinfish (Coryphaena hippurus Linnaeus, 1758), as well as in the sensory characteristics of this food was ...evaluated after using refined or herbal salts, by analyzing the differences in its fatty acid contents, thiobarbituric acid reactive substances (TBARS), product acceptability and consumption intent. Centesimal composition, total phenols and characterization of phenolic compounds were also determined. The cooking caused a significant increase (p < 0.05) in the protein, lipid, ash, whose percentages were higher in fish salt roasted with herbs, compared to fish roasted with refined salt, except for ash. Rutin phenolic compound presented higher concentrations in fish treated with the three herbs. After cooking, the total monounsaturated and polyunsaturated fatty acids of herbal salt-roasted Dolphinfish increased by 128% and 109% compared to refined salt-roasted. TBARS values for salt-roasted gold were 558% higher than in natura and for herbal salt-roasted gold they corresponded to 174%. These results show that the phenolic compounds detected in herbs exerted an antioxidant effect on the preservation of monounsaturated and polyunsaturated fatty acids from fish roasted with herbal salt. Sensory analysis resulted in good acceptability and purchase intent for herbal salt-roasted Dolphinfish.
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