The coronavirus pandemic is a major public health crisis affecting global health systems with dire socioeconomic consequences, especially in vulnerable regions such as Latin America. There is an urgent need for a vaccine to help control contagion, reduce mortality and alleviate social costs. In this study, we propose a rational multi-epitope vaccine against SARS-CoV-2. Using bioinformatics, we constructed a library of potential vaccine peptides to predict immunological complexes among antigenic, non-toxic and non-allergenic peptides extracted from the conserved regions of 92 proteomes. We included the most common HLA-I and II molecules in the Latin American population. We also used three-dimensional structures of SARS-CoV-2 proteins to identify potential regions for antibody production. The best HLA-I and II predictions (with increased coverage in common alleles and regions evoking B lymphocyte responses) were grouped into an optimised nal construct that meets the necessary safety and physicochemical requirements for conducting experimental tests. associated with viral clearance; these alleles facilitate viral antigen presentation and, consequently, the elimination of SARS-CoV mediated by T lymphocytes (TLs) CD8+/CD4+ and natural killer cells 16. From these ndings, we can infer that the preservation of IFN-1 production and some alleles of major human histocompatibility complex 1 and 2 (HLA-I and HLA-II) may be related to the asymptomatic state and the presentation of only mild symptoms in COVID-19 16. In contrast, changes to IFN-1-producing signalling pathways (such as polymorphisms or mutations) that compromise a patient's innate immunity, and differential expression of sex-dependent angiotensinconverting enzyme 2 (ACE2) receptor, may be associated with non-modi able risk factors 17. Virology of SARS-CoV-2 SARS-CoV-2 belongs to the Coronaviridae family and is part of the β group of coronaviruses. It is a 29.9 kb, positivesense, single-stranded, enveloped RNA virus. It is similar to the etiologic agents that cause SARS and Middle East respiratory syndrome (MERS), which share 79.5% and 50% of their identity with SARS-CoV-2, respectively 3,18. Coronavirus genomes are composed of 6-11 open reading frames (ORFs) 19 , with the rst ORF (ORF1a/b) containing two-thirds of the viral RNA. This ORF translates the pp1a and pp1ab polyproteins, and encodes 16 non-structural proteins (NSPs). The other ORFs encode structural and accessory proteins. The genome contains accessory genes: two between the spike surface glycoprotein (SP) and small envelope protein genes (ORF3a and 3b), ve between the matrix protein (MG) and nucleocapsid protein (NP) genes (6, 7a, 7b, 8), 9a and 9b in the NP gene, and 10 after the NP gene 3,20,21. The genome structure is shown in (Supplementary Fig. S1). Medication for COVID-19 An effective treatment against COVID-19 is urgently required; thus, potential medications such as antiviral drugs that can inhibit viral protease 22 , anti-malarial drugs that can inhibit the endosomal entrance of the virus 23 ,...
Graphical abstract SummaryMaternal and/or fetal factors that influence Congenital Zika Syndrome (CZS) development remain elusive. Interferon lambda has been reported as an antiviral factor in Zika infections. Using functional analysis, we conducted a case-control study to demonstrate that maternal interferon lambda single nucleotide polymorphisms (SNPs) contribute to newborn protection. Mothers carrying CA/CC genotypes of rs8109886 SNP have 4.5 times reduced risk of having children with CZS. When we combined the genotypes CC from rs12979860 and CA/CC from rs8109886, 93% of the mothers delivered healthy newborns.Placenta coming from CZS cases displayed diminished level of IFNL2 along with higher tissue-specific type-I IFN genes, tagged by of IFIT5, indicating that lower IFNL levels upon ZIKV infection can lead to uncontrolled damage to overexpression of type-I IFN pathway.In summary, genetically regulated IFNL levels contribute to immune homeostasis and CZS prevention.
Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been posing a serious threat to public health worldwide as the causative agent of coronavirus disease 2019 . Now distributed in a pandemic pattern, this disease still lacks an effective drug treatment with low toxicity, leading pharmaceutical companies and research labs to work against time to find a candidate molecule to efficiently treat the affected patients. Due to the well-known broad-spectrum antimicrobial activity of the lactoferrin protein, we sought to verify whether its bovine form (bLf) would also be effective in vitro against SARS-CoV-2. Using an antiviral assay based on quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we found that bLf reduced progeny virus yield by up to ~84,6% in African green monkey kidney epithelial cells (Vero E6) and ~68,6% in adenocarcinomic human alveolar basal epithelial cells (A549) at 1 mg/mL, a concentration previously shown to have low cytotoxicity. Therefore, our preliminary data suggest that bLf has the potential to constitute a biochemical approach to fight the new coronavirus pandemic. _______________________________________________________________________________________
Zika virus (ZIKV), an arthropod-borne flavivirus, was classified as reemerging infectious disease and included as neglected tropical disease. During the recent ZIKV outbreak in South America, it has been demonstrated that ZIKV infection during pregnancy is strongly associated with fetal loss, malformations and neurological disorders in newborns. Despite the first line of host immune defense is related to innate immunity activation, the immunological homeostasis is essential for pregnancy success. Although the dynamic changes in maternal-fetal immunity is not completely understood and poorly investigated, the knowledge of immune responses during gestation is very important for infectious disease prevention and control, as ZIKV. Here, we put together more and new information about the innate immunity during gestation, highlighting three parts probably involved with clinical outcome and/or not well explored in literature: 1) type III interferon; 2) innate regulatory cells; and 3) cell death pathways modulation. Additionally, we will be focused on discussing how the dynamic responses of innate immune system during pregnancy and its effects in newborns, could be modulated by ZIKV, as well as how efforts on development of new/old drugs and vaccines could be effective for ZIKV prevention and control to provide a successful pregnancy.
The immune response is crucial for coronavirus disease 19 (COVID‐19) progression, with the participation of proinflammatory cells and cytokines, inducing lung injury and loss of respiratory function. CLEC5A expression on monocytes can be triggered by viral and bacterial infections, leading to poor outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is able to induce neutrophil activation by CLEC5A and Toll‐like receptor 2, leading to an aggressive inflammatory cascade, but little is known about the molecular interactions between CLEC5A and SARS‐CoV‐2 proteins. Here, we aimed to explore how CLEC5A expression could be affected by SARS‐CoV‐2 infection using immunological tools with in vitro, in vivo, and in silico assays. The findings revealed that high levels of CLEC5A expression were found in monocytes from severe COVID‐19 patients in comparison with mild COVID‐19 and unexposed subjects, but not in vaccinated subjects who developed mild COVID‐19. In hamsters, we detected CLEC5A gene expression during 3–15 days of Omicron strain viral challenge. Our results also showed that CLEC5A can interact with SARS‐CoV‐2, promoting inflammatory cytokine production, probably through an interaction with the receptor‐binding domain in the N‐acetylglucosamine binding site (NAG‐601). The high expression of CLEC5A and high levels of proinflammatory cytokine production were reduced in vitro by a human CLEC5A monoclonal antibody. Finally, CLEC5A was triggered by spike glycoprotein, suggesting its involvement in COVID‐19 progression; therapy with a monoclonal antibody could be a good strategy for COVID‐19 treatment, but vaccines are still the best option to avoid hospitalization/deaths.
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