Design of a Multi-Epitope Vaccine against Tuberculosis from Mycobacterium tuberculosis PE_PGRS49 and PE_PGRS56 Proteins by Reverse Vaccinology.

Tuberculosis is a disease caused by Mycobacterium tuberculosis, representing the second leading cause of death by an infectious agent worldwide. The available vaccine against this disease has insufficient coverage and variable efficacy, accounting for a high number of cases worldwide. In fact, an estimated third of the world's population has a latent infection. Therefore, developing new vaccines is crucial to preventing it. In this study, the highly antigenic PE_PGRS49 and PE_PGRS56 proteins were analyzed. These proteins were used for predicting T- and B-cell epitopes and for human leukocyte antigen (HLA) protein binding efficiency. Epitopes GGAGGNGSLSS, FAGAGGQGGLGG, GIGGGTQSATGLG (PE_PGRS49), and GTGWNGGKGDTG (PE_PGRS56) were selected based on their best physicochemical, antigenic, non-allergenic, and non-toxic properties and coupled to HLA I and HLA II structures for in silico assays. A construct with an adjuvant (RS09) plus each epitope joined by GPGPG linkers was designed, and the stability of the HLA-coupled construct was further evaluated by molecular dynamics simulations. Although experimental and in vivo studies are still necessary to ensure its protective effect against the disease, this study shows that the vaccine construct is dynamically stable and potentially effective against tuberculosis.

Chikungunya nsP4 homology modeling reveals a common motif with Zika and Dengue RNA polymerases as a potential therapeutic target.

Among the diseases transmitted by vectors, there are those caused by viruses named arboviruses (arthropod-borne viruses). In past years, viruses transmitted by mosquitoes have been of relevance in global health, such as Chikungunya (CHIKV), Dengue (DENV), and Zika (ZIKV), which have Aedes aegypti as a common vector, thus raising the possibility of multi-infection. Previous reports have described the general structure of RNA-dependent RNA polymerases termed right-hand fold, which is conserved in positive single-stranded RNA viruses. Here, we report a comparison between sequences and the computational structure of RNA-dependent RNA polymerases from CHIKV, DENV, and ZIKV and the conserved sites to be considered for the design of an antiviral drug against the three viruses. We show that the sequential identity between consensus sequences from CHIKV and DENV is 8.1% and the similarity is 15.1%; the identity between CHIKV and ZIKV is 9.3%, and the similarity is 16.6%; and the identity between DENV and ZIKV is 68.6%, and the similarity is 79.2%. Nevertheless, the structural alignment shows that the root-mean-square deviation (RMSD) measurement value in general structure comparison between CHIKV RdRp and ZIKV RdRp was 1.248 Å, RMSD between CHIKV RdRp and DENV RdRp was 1.070 Å, and RMSD between ZIKV RdRp and DENV RdRp was 1.106 Å. Despite the low identity and similarity of CHIKV sequence with DENV and ZIKV, we show that A, B, C, and E motifs are structurally well conserved. These structural similarities offer a window into drug design against these arboviruses giving clues about critical target sites.

[Comparative genomic analysis: from SARS to SARS-CoV-2 virus-types. Similarities and differences]. / Análisis de genómica comparativa: del virus SARS al SARS-CoV-2. Similitudes y diferencias.

BACKGROUND: We are currently witnessing a worldwide event caused by the pandemic outbreak derived from the new SARS-CoV-2 virus, which requires the generation of knowledge. Due to its novelty, many hypotheses and theories are discussed daily regarding the origin of this new virus. Several studies are focused on demonstrating how similar it is to other viruses. OBJECTIVE: To highlight the differences of SARS-CoV-2 with other SARS viruses, from a comparative genomics analysis, and determine if these can be attributed to manipulation events. MATERIAL AND METHODS: Complete genomes of two SARS viruses were downloaded, along with other six of human coronaviruses, and 16 of SARS-type coronaviruses. These were analyzed using the BLAST Ring Image Generator tool; afterwards, the evident differences were examined by MAFFT and BLAST programs. RESULTS: High identity was observed in fragments of the mammalian SARS-like genomes with the SARS-CoV-1 and SARS-CoV-2 genomes, identifying three main nucleotide differences, in the ORF1ab nsp3 region gene, in the receptor recognition S gene, and in the ORF8 gene, with which the SARS-type strains of mammals can be separated into the SARS-CoV-1 and SARS-CoV-2 type. CONCLUSION: The complete SARS-CoV-2 genome has high identity with mammalian SARS-type strains, which is why its most probable appearance could be the result of natural evolution.

INTRODUCCIÓN: en este momento somos testigos de un evento de magnitud mundial provocado por el brote pandémico derivado del nuevo virus SARS-CoV-2, lo cual requiere la generación de conocimiento. Por lo novedoso que resulta, muchas hipótesis y teorías son discutidas a diario respecto al origen de este nuevo virus. Varios estudios están enfocados en demostrar la similitud que el SARS-CoV-2 tiene con otros virus. OBJETIVO: resaltar las diferencias del SARS-CoV-2 con otros virus SARS, a partir de un análisis de genómica comparativa, y determinar si se pueden atribuir a eventos de manipulación. MATERIAL Y MÉTODOS: se descargaron dos genomas completos de virus SARS, seis genomas completos de coronavirus humanos y 16 de coronavirus tipo SARS; fueron analizados en un estudio de genómica comparativa mediante la herramienta BLAST Ring Image Generator, y a continuación se examinaron las diferencias evidentes mediante el uso de los programas MAFFT y BLAST. RESULTADOS: se observó una alta identidad en fragmentos de los genomas tipo SARS de mamíferos con los genomas SARS-CoV-1 y SARS-CoV-2, y se identificaron tres diferencias nucleotídicas principales: en el gen ORF1ab región nsp3, en el gen S de reconocimiento al receptor y en el gen ORF8, con el cual se pueden separar las cepas tipo SARS de mamíferos en tipo SARS-CoV-1 y SARS-CoV-2. CONCLUSIÓN: el genoma completo de SARS-CoV-2 posee una alta identidad con cepas tipo SARS de mamíferos, por lo que su aparición más probable podría ser el resultado de la evolución natural.