SARS-CoV-2 is a novel β-coronavirus that caused the COVID-19 pandemic disease, which spread rapidly, infecting more than 134 million people, and killing almost 2.9 million thus far. Based on the urgent need for therapeutic and prophylactic strategies, the identification and characterization of antibodies has been accelerated, since they have been fundamental in treating other viral diseases. Here, we summarized in an integrative manner the present understanding of the immune response and physiopathology caused by SARS-CoV-2, including the activation of the humoral immune response in SARS-CoV-2 infection and therefore, the synthesis of antibodies. Furthermore, we also discussed about the antibodies that can be generated in COVID-19 convalescent sera and their associated clinical studies, including a detailed characterization of a variety of human antibodies and identification of antibodies from other sources, which have powerful neutralizing capacities. Accordingly, the development of effective treatments to mitigate COVID-19 is expected. Finally, we reviewed the challenges faced in producing potential therapeutic antibodies and nanobodies by cell factories at an industrial level while ensuring their quality, efficacy, and safety.
Materials and methods:The dichloromethanic extract of aerial parts of A. confertiflora was separated using chromatography columns. Mycobactericidal activity of the isolated compounds was evaluated using the Alamar Blue bioassay (128-16 lg/mL, 7 days). Cytotoxicity was tested against normal cell line L929 using the MTT ([3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium]) assay (100-3.125 lg/mL, 48 h). , 104-2010, 63-2009, 366-2009 and 430-2010 Mtb strains, respectively. Santamarine had MBCs of 128 lg/mL against the H3Rv and 104-2010 Mtb strains and MICs of 128 lg/mL against the H37Rv, 366-2009 and 104-2010 Mtb strains. We also isolated 1,10-epoxyparthenolide but only showed mycobacteriostatic activity (MIC 128 lg/mL) against the Mtb strain. Compounds were tested against the L929 cell line and the calculated selectivity index was <1. Discussion and conclusions: This is the first report of the mycobactericidal activity of these compounds against clinical Mtb strains. It is also the first report of the isolation of 1,10-epoxyparthenolide from A. confertiflora. The anti-mycobacterial activity of A. confertiflora was attributed to the SQLs identified.ARTICLE HISTORY
BackgroundSonoran ethnic groups (Yaquis, Mayos, Seris, Guarijíos, Pimas, Kikapúes and Pápagos) use mainly herbal based preparations as their first line of medicinal treatment. Among the plants used are those with anti-tuberculosis properties; however, no formal research is available.MethodsOrganic extracts were obtained from nine medicinal plants traditionally used by Sonoran ethnic groups to treat different kinds of diseases; three of them are mainly used to treat tuberculosis. All of the extracts were tested against Mycobacterium tuberculosis H37Rv using the Alamar Blue redox bioassay.ResultsMethanolic extracts from Ambrosia confertiflora, Ambrosia ambrosioides and Guaiacum coulteri showed minimal inhibitory concentration (MIC) values of 200, 790 and 1000 μg/mL, respectively, whereas no effect was observed with the rest of the methanolic extracts at the concentrations tested. Chloroform, dichloromethane, and ethyl acetate extracts from Ambrosia confertiflora showed a MIC of 90, 120 and 160 μg/mL, respectively.ConclusionsA. confertiflora and A. ambrosioides showed the best anti-mycobacterial activity in vitro. The activity of Guaiacum coulteri is consistent with the traditional use by Sonoran ethnic groups as anti-tuberculosis agent.For these reasons, it is important to investigate a broader spectrum of medicinal plants in order to find compounds active against Mycobacterium tuberculosis.
In recent years, knowledge of the role that protein methylation is playing on the physiopathogenesis of bacteria has grown. In Mycobacterium tuberculosis, methylation of the heparin binding hemagglutinin adhesin modulates the immune response, making this protein a subunit vaccine candidate. Through its C-terminal lysine-rich domain, this surface antigen interacts with heparan sulfate proteoglycans present in non-phagocytic cells, leading to extrapulmonary dissemination of the pathogen. In this study, the adhesin was expressed as a recombinant methylated protein in Rhodococcus erythropolis L88 and it was found associated to lipid droplets when bacteria were grown under nitrogen limitation. In order to delve into the role methylation could have in host–pathogen interactions, a comparative analysis was carried out between methylated and unmethylated protein produced in Escherichia coli. We found that methylation had an impact on lowering protein isoelectric point, but no differences between the proteins were found in their capacity to interact with heparin and A549 epithelial cells. An important finding was that HbhA is a Fatty Acid Binding Protein and differences in the conformational stability of the protein in complex with the fatty acid were observed between methylated and unmethylated protein. Together, these results suggest that the described role for this mycobacteria protein in lipid bodies formation could be related to its capacity to transport fatty acids. Obtained results also provide new clues about the role HbhA methylation could have in tuberculosis and point out the importance of having heterologous expression systems to obtain modified proteins.
The objective of this study was to evaluate the antibacterial and antimycobacterial potential of the by-products of white shrimp (Litopenaeus vannamei). Sonora, México is the second shrimp producer state. The following extracts were obtained: exoskeleton hexanic, methanolic and acqueous extracts (ExHex, ExMe, ExAc); and cephalothorax hexanic, acetonic and methanolic extracts (CeHex, CeAce, CeMe). Antibacterial effect was determined by the broth microdilution method against Gram-positive bacteria: Enterococcus faecalis American Type Culture Collection (ATCC) 51299, Staphylococcus aureus ATCC 25293, and Staphylococcus epidermidis; Gram-negative bacteria: Escherichia coli ATCC 25922, Klebsiella pneumoniae, Pseudomonas aeruginosa ATCC 10145, and Salmonella typhimurium; and Mycobacterium bovis bacillus Calmette-Guérin (M. bovis BCG) Danish strain. CeHex resulted active against all Gram-positive and Gram-negative bacteria (MIC50= 400 ug mL-1) and against M. bovis BCG (MIC100= 250 ug mL-1). Gas chromatography (GC) of CeHex identified oleic, linoleic, palmitic, stearic, behenic, palmitoleic and linolenic fatty acids. The strong antibacterial activity of CeHex and the identification of its main chemical constituents justify further studies on the clinical applications of this marine by-product.
Los anticuerpos monoclonales son una de las herramientas más revolucionarias en el área de la biomedicina por tener aplicaciones inmunoterapéuticas e inmunodiagnósticas. Sin embargo, el rápido avance tecnológico que demandan estas áreas genera la exploración de nuevas biomoléculas. El descubrimiento de anticuerpos compuestos únicamente por cadenas pesadas, presentes de forma natural en el suero de los camélidos y en algunas especies de tiburón, son motivo de estudio desde las últimas décadas como una alternativa a los anticuerpos convencionales. Estos poseen una región de reconocimiento antigénico, que consiste en un dominio variable por cada cadena, conocidos como anticuerpos de un solo dominio o nanoanticuerpos. Estas biomoléculas se caracterizan por tener un tamaño reducido, alta especificidad, estabilidad y bajo costo en su producción; propiedades que las convierten en una herramienta altamente versátil. En la presente revisión se abordarán aspectos relevantes de los nanoanticuerpos, como su descubrimiento, características estructurales, desarrollo en el campo de la biotecnología y su potencial de aplicación en enfermedades como el cáncer y en la identificación de microorganismos.
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