A higher number of SARS-COV-2 infections in quilombola communities than in the local population in Brazil.

The historical and social vulnerability of quilombola communities in Brazil can make them especially fragile in the face of COVID-19, considering that several individuals have precarious health systems and inadequate access to water. This work aimed to characterize the frequency of SARS-COV-2 infections and the presence of IgM and IgG SARS-CoV-2 antibodies in quilombola populations and their relationship with the presence of risk factors or preexisting chronic diseases in the quilombola communities. We analyzed the sociodemographic and clinical characteristics, serological status, comorbidities, and symptoms of 1,994 individuals (478 males and 1,536 females) from 18 Brazilian municipalities in the State of Sergipe of quilombola communities, which were evaluated at different epidemiological weeks, starting at the 32nd (August 6th) and ending at the 40th (October 3rd) epidemiological week. More than 70% of studied families live in rural areas and they have an extreme poverty social status. Although we found a higher number of SARS-COV-2 infections in quilombola communities than in the local population, their SARS-CoV-2 reactivity and IgM and IgG positivity varied across the communities investigated. Arterial hypertension was the most risk factor, being found in 27.8% of the individuals (9.5% in stage 1, 10.8% in stage 2, and 7.5% in stage 3). The most common COVID-19 symptoms and comorbidities were headache, runny nose, flu, and dyslipidemia. However, most individuals were asymptomatic (79.9%). Our data indicate that mass testing must be incorporated into public policy to improve the health care system available to quilombola populations during a future pandemic or epidemic.

Integrative transcriptome analysis of SARS-CoV-2 human-infected cells combined with deep learning algorithms identifies two potential cellular targets for the treatment of coronavirus disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly spread worldwide, leading coronavirus disease 2019 (COVID-19) to hit pandemic level less than 4 months after the first official cases. Hence, the search for drugs and vaccines that could prevent or treat infections by SARS-CoV-2 began, intending to reduce a possible collapse of health systems. After 2 years, efforts to find therapies to treat COVID-19 continue. However, there is still much to be understood about the virus' pathology. Tools such as transcriptomics have been used to understand the impact of SARS-CoV-2 on different cells isolated from various tissues, leaving datasets in the databases that integrate genes and differentially expressed pathways during SARS-CoV-2 infection. After retrieving transcriptome datasets from different human cells infected with SARS-CoV-2 available in the database, we performed an integrative analysis associated with deep learning algorithms to determine differentially expressed targets mainly after infection. The targets found represented a fructose transporter (GLUT5) and a component of proteasome 26s. These targets were then molecularly modeled, followed by molecular docking that identified potential inhibitors for both structures. Once the inhibition of structures that have the expression increased by the virus can represent a strategy for reducing the viral replication by selecting infected cells, associating these bioinformatics tools, therefore, can be helpful in the screening of molecules being tested for new uses, saving financial resources, time, and making a personalized screening for each infectious disease.

SARS-CoV-2 mutations and where to find them: an in silico perspective of structural changes and antigenicity of the spike protein.

Communicated by Ramaswamy H. Sarma.

Rapid diagnosis of COVID-19 in the first year of the pandemic: A systematic review.

BACKGROUND: COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health threat and remains a challenge for modern medicine. Rapid and accurate diagnosis of COVID-19 is vital for proper disease and outbreak management. Our review aimed to analyze scientific articles published in the literature addressing the rapid tests available for COVID-19 diagnosis at the first year of the pandemic. METHODS: A systematic review was performed from October 22 to 27, 2020, searching data published in PubMed and Google Scholar databases, using subject headings or keywords related to point of care and rapid test diagnostic for SARS-CoV-2 and COVID-19. RESULTS: The first survey identified 403 articles, but only 23 met the defined criteria for the systematic analysis. The sensitivity and specificity parameters were assessed in 19 studies, and the data suggested that there was lower sensitivity in the period 1 to 7 days after the emergence of symptoms (∼38%) higher sensitivity at 8 to 14 days (∼90%), and the highest at 15 to 39 days (∼98%). Accuracy was reported in six studies, reporting values above 50%. Only three studies reported a possible cross-reaction. CONCLUSIONS: Our findings indicate that the rapid tests used in the first year of the pandemic were tested with a small number of samples and not adequately validated. And the studies that described them were conducted with little scientific rigor.

Isohemigossypolone: Antiophidic properties of a naphthoquinone isolated from Pachira aquatica Aubl.

We investigated the antiophidic properties of isohemigossypolone (ISO), a naphthoquinone isolated from the outer bark of the Pachira aquatic Aubl. The inhibition of phospholipase A2, coagulant, fibrinogenolytic, hemorrhagic and myotoxic activities induced by Bothrops pauloensis venom (Pb) was investigated. For this, we use samples resulting from the incubation of Pb with ISO in different concentrations (1:1, 1:5 and 1:10 w/w), we also evaluated the condition of treatment using ISO after 15 min of venom inoculation. The activities of phospholipase A2, coagulant, fibrinogenolytic, hemorrhagic and myotoxic induced by the B. pauloensis venom were significantly inhibited when the ISO was pre-incubated with the crude venom. For in vivo neutralization tests, the results were observed even when the ISO was applied after 15 min of inoculation of the venom or metalloprotease (BthMP). Also, to identify the inhibition mechanism, we performed in silico assays, across simulations of molecular coupling and molecular dynamics, it was possible to identify the modes of interaction between ISO and bothropic toxins BmooMPα-I, Jararacussin-I and BNSP-7. The present study shows that naphthoquinone isohemigossypolone isolated from the P. aquatica plant inhibited part of the local and systemic damage caused by venom proteins, demonstrating the pharmacological potential of this compound in neutralizing the harmful effects caused by snakebites.

Nanoparticles as Vaccines to Prevent Arbovirus Infection: A Long Road Ahead.

Arthropod-borne viruses (arboviruses) are a significant public health problem worldwide. Vaccination is considered one of the most effective ways to control arbovirus diseases in the human population. Nanoparticles have been widely explored as new vaccine platforms. Although nanoparticles' potential to act as new vaccines against infectious diseases has been identified, nanotechnology's impact on developing new vaccines to prevent arboviruses is unclear. Thus, we used a comprehensive bibliographic survey to integrate data concerning the use of diverse nanoparticles as vaccines against medically important arboviruses. Our analysis showed that considerable research had been conducted to develop and evaluate nanovaccines against Chikungunya virus, Dengue virus, Zika virus, Japanese encephalitis virus, and West Nile virus. The main findings indicate that nanoparticles have great potential for use as a new vaccine system against arboviruses. Most of the studies showed an increase in neutralizing antibody production after mouse immunization. Nevertheless, even with significant advances in this field, further efforts are necessary to address the nanoparticles' potential to act as a vaccine against these arboviruses. To promote advances in the field, we proposed a roadmap to help researchers better characterize and evaluate nanovaccines against medically important arboviruses.

Dynamic behavior of Dengue and Zika viruses NS1 protein reveals monomer-monomer interaction mechanisms and insights to rational drug design.

Communicated by Ramaswamy H. Sarma.

Mutation of critical residues reveals insights of yellow fever virus nonstructural protein 1 (NS1) stability and its formation.

Communicated by Ramaswamy H. Sarma.

Alkaloids as inhibitors of malate synthase from Paracoccidioides spp.: receptor-ligand interaction-based virtual screening and molecular docking studies, antifungal activity, and the adhesion process.

Paracoccidioides is the agent of paracoccidioidomycosis. Malate synthase plays a crucial role in the pathogenicity and virulence of various fungi, such as those that are human pathogens. Thus, an inhibitor of this enzyme may be used as a powerful antifungal without side effects in patients once these enzymes are absent in humans. Here, we searched for compounds with inhibitory capacity against the malate synthase of Paracoccidioides species (PbMLS). The three-dimensional (3D) structure of PbMLS was determined using the I-TASSER server. Compounds were selected from the ZINC database. Based on the mechanism underlying the interaction of the compounds with PbMLS, it was possible to identify ß-carboline moiety as a standard key structure. The compounds with ß-carboline moiety that are available in our laboratories were investigated. A total of nine alkaloid compounds were selected. The primary mechanisms of interaction of the alkaloid compounds in the binding pocket of PbMLS were identified and compared with the mechanism of interaction of acetyl coenzyme A (acetyl-CoA). We discovered that the amphipathic nature of the compounds, concomitant with the presence of ß-carboline moiety, was crucial for their stability in the binding pocket of PbMLS. In addition, the importance of a critical balance of the polar and nonpolar contacts of the compounds in this region was observed. Four ß-carboline alkaloid compounds showed the ability to inhibit recombinant PbMLS (PbMLSr) activity, Paracoccidioides species growth, and adhesion of the fungus and PbMLSr to the extracellular matrix components. The cytotoxicity of the alkaloids was also evaluated.