The genomic sequences of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) worldwide are publicly available and are derived from studies due to the increase in the number of cases. The importance of study of mutations is related to the possible virulence and diagnosis of SARS‐CoV‐2. To identify circulating mutations present in SARS‐CoV‐2 genomic sequences in Mexico, Belize, and Guatemala to find out if the same strain spread to the south, and analyze the specificity of the primers used for diagnosis in these samples. Twenty three complete SARS‐CoV‐2 genomic sequences, available in the GISAID database from May 8 to September 11, 2020 were analyzed and aligned versus the genomic sequence reported in Wuhan, China (NC_045512.2), using Clustal Omega. Open reading frames were translated using the ExPASy Translate Tool and UCSF Chimera (v.1.12) for amino acid substitutions analysis. Finally, the sequences were aligned versus primers used in the diagnosis of COVID‐19. One hundred and eighty seven distinct variants were identified, of which 102 are missense, 66 synonymous and 19 noncoding. P4715L and P5828L substitutions in replicase polyprotein were found, as well as D614G in spike protein and L84S in ORF8 in Mexico, Belize, and Guatemala. The primers design by CDC of United States showed a positive E value. The genomic sequences of SARS‐CoV‐2 in Mexico, Belize, and Guatemala present similar mutations related to a virulent strain of greater infectivity, which could mean a greater capacity for inclusion in the host genome and be related to an increased spread of the virus in these countries, furthermore, its diagnosis would be affected.

No abstract

Numerous repositioned drugs have been sought to decrease the severity of SARS-CoV-2 infection. It is known that among its physicochemical properties, Ursodeoxycholic Acid (UDCA) has a reduction in surface tension and cholesterol solubilization, it has also been used to treat cholesterol gallstones and viral hepatitis. In this study, molecular docking was performed with the SARS-CoV-2 Spike protein and UDCA. In order to confirm this interaction, we used Molecular Dynamics (MD) in “SARS-CoV-2 Spike protein-UDCA”. Using another system, we also simulated MD with six UDCA residues around the Spike protein at random, naming this “SARS-CoV-2 Spike protein-6UDCA”. Finally, we evaluated the possible interaction between UDCA and different types of membranes, considering the possible membrane conformation of SARS-CoV-2, this was named “SARS-CoV-2 membrane-UDCA”. In the “SARS-CoV-2 Spike protein-UDCA”, we found that UDCA exhibits affinity towards the central region of the Spike protein structure of − 386.35 kcal/mol, in a region with 3 alpha helices, which comprises residues from K986 to C1032 of each monomer. MD confirmed that UDCA remains attached and occasionally forms hydrogen bonds with residues R995 and T998. In the presence of UDCA, we observed that the distances between residues atoms OG1 and CG2 of T998 in the monomers A, B, and C in the prefusion state do not change and remain at 5.93 ± 0.62 and 7.78 ± 0.51 Å, respectively, compared to the post-fusion state. Next, in “SARS-CoV-2 Spike protein-6UDCA”, the three UDCA showed affinity towards different regions of the Spike protein, but only one of them remained bound to the region between the region's heptad repeat 1 and heptad repeat 2 (HR1 and HR2) for 375 ps of the trajectory. The RMSD of monomer C was the smallest of the three monomers with a value of 2.89 ± 0.32, likewise, the smallest RMSF was also of the monomer C (2.25 ± 056). In addition, in the simulation of “SARS-CoV-2 membrane-UDCA”, UDCA had a higher affinity toward the virion-like membrane; where three of the four residues remained attached once they were close (5 Å, to the centre of mass) to the membrane by 30 ns. However, only one of them remained attached to the plasma-like membrane and this was in a cluster of cholesterol molecules. We have shown that UDCA interacts in two distinct regions of Spike protein sequences. In addition, UDCA tends to stay bound to the membrane, which could potentially reduce the internalization of SARS-CoV-2 in the host cell.

SARS-CoV-2 contains certain molecules that are related to the presence of immunothrombosis. Here, we review the pathogen and damage-associated molecular patterns. We also study the imbalance of different molecules participating in immunothrombosis, such as tissue factor, factors of the contact system, histones, and the role of cells, such as endothelial cells, platelets, and neutrophil extracellular traps. Regarding the pathogenetic mechanism, we discuss clinical trials, case-control studies, comparative and translational studies, and observational studies of regulatory or inhibitory molecules, more specifically, extracellular DNA and RNA, histones, sensors for RNA and DNA, as well as heparin and heparinoids. Overall, it appears that a network of cells and molecules identified in this axis is simultaneously but differentially affecting patients at different stages of COVID-19, and this is characterized by endothelial damage, microthrombosis, and inflammation.

Chagas and COVID-19 are diseases caused by Trypanosoma cruzi and SARS-CoV-2, respectively. These diseases present very different etiological agents despite showing similarities such as susceptibility/risk factors, pathogen-associated molecular patterns (PAMPs), recognition of glycosaminoglycans, inflammation, vascular leakage hypercoagulability, microthrombosis, and endotheliopathy; all of which suggest, in part, treatments with similar principles. Here, both diseases are compared, focusing mainly on the characteristics related to dysregulated immunothrombosis. Given the in-depth investigation of molecules and mechanisms related to microthrombosis in COVID-19, it is necessary to reconsider a prompt treatment of Chagas disease with oral anticoagulants.

No abstract

Ageing is associated with changes in body composition, such as low muscle mass (sarcopenia), decreased grip strength or physical function (dynapenia), and accumulation of fat mass. When the accumulation of fat mass synergistically accompanies low muscle mass or reduced grip strength, it results in sarcopenic obesity and dynapenic obesity, respectively. These types of obesity contribute to the increased risk of cardiovascular disease and mortality in the elderly, which could increase the damage caused by COVID-19. In this review, we associated factors that could generate a higher risk of COVID-19 complications in dynapenic obesity and sarcopenic obesity. For example, skeletal muscle regulates the expression of inflammatory cytokines and supports metabolic stress in pulmonary disease; hence, the presence of dynapenic obesity or sarcopenic obesity could be related to a poor prognosis in COVID-19 patients.

Glycosylation is a post-translational modification that affects the stability, structure, antigenicity and charge of proteins. In the immune system, glycosylation is involved in the regulation of ligand–receptor interactions, such as in B-cell and T-cell activating receptors. Alterations in glycosylation have been described in several autoimmune diseases, such as systemic lupus erythematosus (SLE), in which alterations have been found mainly in the glycosylation of B lymphocytes, T lymphocytes and immunoglobulins. In immunoglobulin G of lupus patients, a decrease in galactosylation, sialylation, and nucleotide fucose, as well as an increase in the N-acetylglucosamine bisector, are observed. These changes in glycoisolation affect the interactions of immunoglobulins with Fc receptors and are associated with pericarditis, proteinuria, nephritis, and the presence of antinuclear antibodies. In T cells, alterations have been described in the glycosylation of receptors involved in activation, such as the T cell receptor; these changes affect the affinity with their ligands and modulate the binding to endogenous lectins such as galectins. In T cells from lupus patients, a decrease in galectin 1 binding is observed, which could favor activation and reduce apoptosis. Furthermore, these alterations in glycosylation correlate with disease activity and clinical manifestations, and thus have potential use as biomarkers. In this review, we summarize findings on glycosylation alterations in SLE and how they relate to immune system defects and their clinical manifestations.