SARS-CoV-2 variants, its recombinants and epigenomic exploitation of host defenses.

Since 2003, we have seen the emergence of novel viruses, such as SARS-CoV-1, MERS, ZIKA, swine flu virus H1N1, Marburg, Monkeypox, Ebola, and SARS-CoV-2, but none of them gained pandemic proportions similar to SARS-CoV-2. This could be attributed to unique viral traits, allowing its rapid global dissemination following its emergence in October 2019 in Wuhan, China, which appears to be primarily driven by the emergence of highly transmissible and virulent variants that also associate, in some cases, with severe disease and considerable mortality caused by fatal pneumonia, acute respiratory distress syndrome (ARDS) in infected individuals. Mechanistically, several factors are involved in viral pathogenesis, and epigenetic alterations take the front seat in host-virus interactions. The molecular basis of all viral infections, including SARS-CoV-2, tightly hinges on the transitory silencing of the host gene machinery via epigenetic modulation. SARS-CoV-2 also hijacks and subdues the host gene machinery, leading to epigenetic modulation of the critical host elements responsible for antiviral immunity. Epigenomics is a powerful, unexplored avenue that can provide a profound understanding of virus-host interactions and lead to the development of epigenome-based therapies and vaccines to counter viruses. This review discusses current developments in SARS-CoV-2 variation and its role in epigenetic modulation in infected hosts. This review provides an overview, especially in the context of emerging viral strains, their recombinants, and their possible roles in the epigenetic exploitation of host defense and viral pathogenesis. It provides insights into host-virus interactions at the molecular, genomic, and immunological levels and sheds light on the future of epigenomics-based therapies for SARS-CoV-2 infection.

Therapeutic potential of metal ions for COVID-19: insights from the papain-like protease of SARS-CoV-2.

Coronaviruses have been responsible for multiple challenging global pandemics, including coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Papain-like protease (PLpro), one of two cysteine proteases responsible for the maturation and infectivity of SARS-CoV-2, processes and liberates functional proteins from the viral polyproteins and cleaves ubiquitin and ISG15 modifications to inhibit innate immune sensing. Consequently, PLpro is an attractive target for developing COVID-19 therapies. PLpro contains a zinc-finger domain important for substrate binding and structural stability. However, the impact of metal ions on the activity and biophysical properties of SARS-CoV-2 PLpro has not been comprehensively studied. Here, we assessed the impacts of metal ions on the catalytic activity of PLpro. Zinc had the largest inhibitory effect on PLpro, followed by manganese. Calcium, magnesium, and iron had smaller or no effects on PLpro activity. EDTA at a concentration of 0.5 mM was essential for PLpro activity, likely by chelating trace metals that inhibit PLpro. IC50 values for ZnCl2, ZnSO4, and MnCl2 of 0.42 ± 0.02 mM, 0.35 ± 0.01 mM, and 2.6 ± 0.3 mM were obtained in the presence of 0.5 mM EDTA; in the absence of EDTA, the estimated IC50 of ZnCl2 was 14 µM. Tryptophan intrinsic fluorescence analysis confirmed the binding of zinc and manganese to PLpro, and differential scanning calorimetry revealed that zinc but not manganese reduced ΔHcal of PLpro. The results of this study provide a reference for further work targeting PLpro to prevent and treat COVID-19.

Use of the FLOTAC technique as a new coproparasitological diagnostic method in aquatic mammals and comparison with traditional methods.

The inadequate choice of a diagnostic method or the option for techniques that have low sensitivity and specificity may limit the diagnosis of parasitic agents that affect aquatic mammals. The aim of this study was to evaluate the performance of the FLOTAC technique and compare it with three traditional methods (Willis, sedimentation and centrifugation- flotation) used in the diagnosis of gastrointestinal parasites in aquatic mammals. For this, 129 fecal samples from 12 species were collected. Each sample was submitted to laboratory processing using the Willis, Hoffman techniques, Faust method and FLOTAC. Sensitivity, specificity, real prevalence, estimated prevalence, positive predictive value, negative predictive value, correct classification (accuracy) and incorrect classification were evaluated to compare the different diagnostic methods. The highest frequency of positive samples occurred using FLOTAC (46.51%), compared to Hoffman (23.25%), Faust (10.07%) and Willis techniques (6.97%). In the samples analyzed, the occurrence of Strongylidae eggs and Eimeriidae oocysts was frequently observed. The FLOTAC technique proved to be the most appropriate technique and due to its efficacy, is strongly recommended for coproparasitological evaluations in aquatic mammals.

Ceratocystis cacaofunesta differentially modulates the proteome in xylem-enriched tissue of cocoa genotypes with contrasting resistance to Ceratocystis wilt.

MAIN CONCLUSION: Decreased accumulation of polyphenol oxidase, H2O2 accumulation, effective regulation of programmed cell death, and a protein predicted as allergenic can play key roles in cacao defense against Ceratocystis cacaofunesta. Ceratocystis wilt, caused by the fungus Ceratocystis cacaofunesta, has destroyed millions of Theobroma cacao trees in several countries of the Americas. Through proteomics, systems biology, and enzymatic analyses of infected stems, it was possible to infer mechanisms used by resistant (TSH1188) and susceptible (CCN51) cacao genotypes during infection. Protein extraction from xylem-enriched tissue of stems inoculated with the fungus and their controls 1 day after inoculation was carried out, followed by separation through two-dimensional gel electrophoresis and identification by mass spectrometry. Enzyme activity was determined at 1, 3, 7 and 15 days after inoculation. A total of 50 differentially accumulated distinct proteins were identified in the treatments of both genotypes and were classified into 10 different categories. An interaction network between homologous proteins from Arabidospsis thaliana was generated for each genotype, using the STRING database and Cytoscape software. Primary metabolism processes were apparently repressed in both genotypes. The resistance factors suggested for genotype TSH1188 were: H2O2 accumulation, effective regulation of programmed cell death, production of phytoalexins derived from tryptophan and furanocoumarins, and participation of a predicted allergenic protein with probable ribonuclease function inhibiting the germination and propagation of the fungus. In the susceptible genotype, it is possible that its recognition and signaling mechanism through proteins from the SEC14 family is easily overcome by the pathogen. Our results will help to better understand the interaction between cacao and one of its most aggressive pathogens, to create disease control strategies.

Soroprevalência de Toxoplasma gondii em equídeos do Nordeste do Brasil / Seroprevalence of Toxoplasma gondii in equidae from Northeast Brazil

Este estudo teve como objetivo determinar a soroprevalência da toxoplasmose em equídeos mantidos em diferentes formas de manejo no estado de Pernambuco. Para tanto, um total de 400 amostras de soro sanguíneo de equídeos clinicamente saudáveis foram analisados através do teste de aglutinação modificado (MAT) considerando-se cut-off de 1:25. Dados referentes às características dos animais e dos rebanhos, sistema de criação, presença de outros animais, idade, sexo, raça, aptidão, condição física foram coletados por meio de questionários investigativos. Anticorpos IgG anti-Toxoplasma gondii foram detectados em 12,5% (50/400) dos animais analisados. Dos 12 municípios estudados, houve positividade em 91,67% (11/12) com variação entre 4,4% e 33,3%. Quando avaliados os fatores de risco, apenas o fator mesorregião (p=0,029) apresentou associação com a infecção, particularmente Zona da Mata (OR=3), seguida de Região Metropolitana do Recife (OR=2,2), Agreste (OR=1,7) e Sertão (OR=1). Os resultados revelam a presença do parasito na área estudada, o que pode representar um elo na cadeia de transmissão da toxoplasmose a qual tem repercussão em saúde pública tendo em vista que o Brasil é o oitavo maior exportador de carne equina do mundo.(AU)

This paper reports seroprevalence of toxoplasmosis in horses kept in different forms of breeding system in the state of Pernambuco. For that, 400 blood serum samples from clinically healthy horses were analyzed through the test of modified agglutination (MAT) considering cut-off of 1:25. Data related to the characteristics of the animals and herds, breeding system, presence of other animals, age, gender, breed, aptitude, and physical conditions were collected throughout investigative surveys. IgG anti-Toxoplasma gondii antibodies were detected in 12.5% (50/400) of the analyzed animals. In the 12 studied towns, there was a positivity in 91. 67% (11/12) with a variation between 4% and 33.3%. When the risk factors were evaluated, only the mesoregion factor (p=0.029) had an association with the infection, particularly the Zona da Mata region (OR=3), followed by the Recife Metropolitan Area (OR=2.2), Agreste region (OR=1.7) and Sertão region (OR=1). The results shows the presence of the parasites on the studied area, which may represent a link with the transmission chain of toxoplasmosis which has influence on the public health system, considering that Brazil is the eighth greatest exporter of equine meat in the world.(AU)