ABSTRACT
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.
Subject(s)
Alarmins , COVID-19/virology , SARS-CoV-2 , Thromboinflammation/virology , Thrombosis/virology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Blood Coagulation , Blood Platelets/virology , COVID-19/complications , DNA/metabolism , Extracellular Traps , Heparin/metabolism , Histones/metabolism , Humans , Mice , Neuropilin-1/metabolism , RNA/metabolism , Signal Transduction , Thrombin/metabolism , Thromboplastin/metabolism , Thrombosis/complicationsABSTRACT
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.
Subject(s)
COVID-19/virology , Genome, Viral , Mutation , SARS-CoV-2/genetics , Belize , COVID-19/diagnosis , DNA Primers , Guatemala , Humans , Mexico , Open Reading Frames , Polymerase Chain ReactionABSTRACT
The disease caused by the new coronavirus (COVID-19) is characterized by fever and cough, in addition to affecting the lower respiratory tract and being associated with age, comorbidities and a weakened immune system. Lymphopenias occur in severe cases and an excessive production of inflammatory cytokines, which would explain the role of the hyperinflammatory response in the pathogenesis of COVID-19. In the absence of treatment for this virus, there is an urgent need to find alternative methods to control the spread of the disease, so we have conducted an online search for all treatment options related to coronavirus infections, as well as some infections due to viruses, general treatments, specific coronavirus treatments and antiviral treatments should be useful in the fight against COVID-19, the therapeutic agents evaluated included chloroquine/hydroxychloroquine, lopinavir/ritonavir, tocilizumab, ribavirin, interferons, nelfinavir, ivermectin, monoclonal antibodies and convalescent plasma. Yeni koronavirüsün (COVID-19) neden olduğu hastalık, alt solunum yolunu etkilemesine ve yaş, komorbiditeler ve zayıflamış bağışıklık sistemi ile ilişkili olmasının yanı sıra ateş ve öksürük ile karakterizedir. Lenfopeniler şiddetli vakalarda ortaya çıkar ve aşırı inflamatuar sitokin üretimi, COVID-19'un patogenezinde hiperinflamatuar yanıtın rolünü açıklar. Bu virüs için tedavi olmadığında, hastalığın yayılmasını kontrol etmek için alternatif yöntemler bulmaya acil ihtiyaç vardır, bu nedenle koronavirüs enfeksiyonlarıyla ilgili tüm tedavi seçenekleri ve virüslere bağlı bazı enfeksiyonlar için çevrimiçi bir araştırma yaptık. COVID-19 ile mücadelede genel tedaviler, spesifik koronavirüs tedavileri ve antiviral tedaviler yararlı olmalıdır;değerlendirilen terapötik ajanlar arasında klorokin / hidroksiklorokin, lopinavir/ritonavir, tocilizumab, rivabirin, interferonlar, nelfinavir, ivermektin, monoklonal antikorlar ve iyileşen plazma yer almaktadır. [ABSTRACT FROM AUTHOR] Copyright of Turkish Journal of Biochemistry / Turk Biyokimya Dergisi is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)