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1.
Infect Dis Poverty ; 10(1): 28, 2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: covidwho-1135002

RESUMEN

BACKGROUND: Coronaviruses (CoVs) are distributed worldwide and have various susceptible hosts; CoVs infecting humans are called human coronaviruses (HCoVs). Although HCoV-specific drugs are still lacking, many potent targets for drug discovery are being explored, and many vigorously designed clinical trials are being carried out in an orderly manner. The aim of this review was to gain a comprehensive understanding of the current status of drug development against HCoVs, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MAIN TEXT: A scoping review was conducted by electronically searching research studies, reviews, and clinical trials in PubMed and the CNKI. Studies on HCoVs and therapeutic drug discovery published between January 2000 and October 2020 and in English or Chinese were included, and the information was summarized. Of the 3248 studies identified, 159 publication were finally included. Advances in drug development against HCoV, especially SARS-CoV-2, are summarized under three categories: antiviral drugs aimed at inhibiting the HCoV proliferation process, drugs acting on the host's immune system, and drugs derived from plants with potent activity. Furthermore, clinical trials of drugs targeting SARS-CoV-2 are summarized. CONCLUSIONS: During the spread of COVID-19 outbreak, great efforts have been made in therapeutic drug discovery against the virus, although the pharmacological effects and adverse reactions of some drugs under study are still unclear. However, well-designed high-quality studies are needed to further study the effectiveness and safety of these potential drugs so as to provide valid recommendations for better control of the COVID-19 pandemic.


Asunto(s)
Antivirales/farmacología , Infecciones por Coronavirus/virología , Coronavirus/efectos de los fármacos , Coronavirus/fisiología , Descubrimiento de Drogas , Antivirales/uso terapéutico , Biomarcadores , /metabolismo , Coronavirus/clasificación , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/metabolismo , Desarrollo de Medicamentos , Descubrimiento de Drogas/métodos , Regulación Viral de la Expresión Génica , Interacciones Huésped-Patógeno , Humanos , Medicina Tradicional , Terapia Molecular Dirigida , Replicación Viral/efectos de los fármacos
2.
Endocr Rev ; 41(3)2020 06 01.
Artículo en Inglés | MEDLINE | ID: covidwho-1110054

RESUMEN

Individuals with diabetes are at increased risk for bacterial, mycotic, parasitic, and viral infections. The severe acute respiratory syndrome (SARS)-CoV-2 (also referred to as COVID-19) coronavirus pandemic highlights the importance of understanding shared disease pathophysiology potentially informing therapeutic choices in individuals with type 2 diabetes (T2D). Two coronavirus receptor proteins, angiotensin-converting enzyme 2 (ACE2) and dipeptidyl peptidase-4 (DPP4) are also established transducers of metabolic signals and pathways regulating inflammation, renal and cardiovascular physiology, and glucose homeostasis. Moreover, glucose-lowering agents such as the DPP4 inhibitors, widely used in subjects with T2D, are known to modify the biological activities of multiple immunomodulatory substrates. Here, we review the basic and clinical science spanning the intersections of diabetes, coronavirus infections, ACE2, and DPP4 biology, highlighting clinical relevance and evolving areas of uncertainty underlying the pathophysiology and treatment of T2D in the context of coronavirus infection.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Neumonía Viral/complicaciones , Animales , Infecciones por Coronavirus/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Tracto Gastrointestinal/metabolismo , Humanos , Insulina/uso terapéutico , Pulmón/metabolismo , Obesidad/complicaciones , Obesidad/metabolismo , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/metabolismo , Receptores Virales/metabolismo , Factores de Riesgo , Serina Endopeptidasas/metabolismo
3.
Trop Biomed ; 37(4): 963-972, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: covidwho-1103244

RESUMEN

Canine Enteric Coronavirus (CCoV) is one of the major enteric pathogen affecting dogs. This study aims to investigate the molecular prevalence, phylogenetic analysis, associated risk factors, and haemato-biochemical alterations in Canine Coronavirus in dogs in district Lahore, Pakistan. 450 fecal samples were collected from symptomatic dogs originating from various pet-clinics and kennels during 2018-2019. Samples were initially analyzed by sandwich lateral flow immunochromatographic assay and then further processed by RT-PCR (reverse transcriptase polymerase chain reaction) targeting the M gene followed by sequencing. RT-PCR based positive (n=20) and negative (n=20) dogs were samples for their blood for the haemato-biochemical analysis. A questionnaire was used to collect data from pet owners, in order to analyze the data for risk factors analysis by chi square test on SPSS. The prevalence of CCoV was 35.1%, and 23.8 % through Sandwich lateral flow immunochromatographic and RT-PCR respectively. Various risk factors like breed, age, sex, vomiting, diarrhea, sample source, body size, cohabitation with other animals, living environment, food, deworming history, contact with other animals or birds feces, and season were significantly associated with CCoV. The CCoV identified in Pakistan were 98% similar with the isolates from China (KT 192675, 1), South Korea (HM 130573, 1), Brazil (GU 300134, 1), Colombia (MH 717721, 1), United Kingdom (JX 082356, 1) and Tunisia (KX156806). Haematobiochemical alterations in CCoV affected dogs revealed anaemia, leucopenia, lymphopenia, neutrophilia, and decreased packed cell volume, and a significant increase in alkaline phosphate and alanine transaminase. It is concluded that infection with canine coronavirus appears widespread among dog populations in district Lahore, Pakistan. This study is the first report regarding the molecular detection and sequence analysis of CCoV in Pakistan.


Asunto(s)
Infecciones por Coronavirus/veterinaria , Coronavirus Canino , Enfermedades de los Perros/virología , Animales , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Coronavirus Canino/genética , Enfermedades de los Perros/sangre , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/metabolismo , Perros , Femenino , Inmunoensayo , Masculino , Pakistán/epidemiología , Filogenia , Prevalencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Factores de Riesgo
4.
Sci Rep ; 11(1): 4108, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: covidwho-1091453

RESUMEN

In December 2019, rising pneumonia cases caused by a novel ß-coronavirus (SARS-CoV-2) occurred in Wuhan, China, which has rapidly spread worldwide, causing thousands of deaths. The WHO declared the SARS-CoV-2 outbreak as a public health emergency of international concern, since then several scientists are dedicated to its study. It has been observed that many human viruses have codon usage biases that match highly expressed proteins in the tissues they infect and depend on the host cell machinery for the replication and co-evolution. In this work, we analysed 91 molecular features and codon usage patterns for 339 viral genes and 463 human genes that consisted of 677,873 codon positions. Hereby, we selected the highly expressed genes from human lung tissue to perform computational studies that permit to compare their molecular features with those of SARS, SARS-CoV-2 and MERS genes. The integrated analysis of all the features revealed that certain viral genes and overexpressed human genes have similar codon usage patterns. The main pattern was the A/T bias that together with other features could propitiate the viral infection, enhanced by a host dependant specialization of the translation machinery of only some of the overexpressed genes. The envelope protein E, the membrane glycoprotein M and ORF7 could be further benefited. This could be the key for a facilitated translation and viral replication conducting to different comorbidities depending on the genetic variability of population due to the host translation machinery. This is the first codon usage approach that reveals which human genes could be potentially deregulated due to the codon usage similarities between the host and the viral genes when the virus is already inside the human cells of the lung tissues. Our work leaded to the identification of additional highly expressed human genes which are not the usual suspects but might play a role in the viral infection and settle the basis for further research in the field of human genetics associated with new viral infections. To identify the genes that could be deregulated under a viral infection is important to predict the collateral effects and determine which individuals would be more susceptible based on their genetic features and comorbidities associated.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/virología , Codón/genética , Uso de Codones , Biología Computacional/métodos , Coronavirus/genética , Infecciones por Coronavirus/metabolismo , Genes Virales , Genoma Viral , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Filogenia , Virus del SRAS/genética , /genética
5.
PLoS One ; 16(2): e0246901, 2021.
Artículo en Inglés | MEDLINE | ID: covidwho-1088759

RESUMEN

The MERS-CoV, SARS-CoV, and SARS-CoV-2 are highly pathogenic viruses that can cause severe pneumonic diseases in humans. Unfortunately, there is a non-available effective treatment to combat these viruses. Domain-motif interactions (DMIs) are an essential means by which viruses mimic and hijack the biological processes of host cells. To disentangle how viruses achieve this process can help to develop new rational therapies. Data mining was performed to obtain DMIs stored as regular expressions (regexp) in 3DID and ELM databases. The mined regexp information was mapped on the coronaviruses' proteomes. Most motifs on viral protein that could interact with human proteins are shared across the coronavirus species, indicating that molecular mimicry is a common strategy for coronavirus infection. Enrichment ontology analysis for protein domains showed a shared biological process and molecular function terms related to carbon source utilization and potassium channel regulation. Some of the mapped motifs were nested on B, and T cell epitopes, suggesting that it could be as an alternative way for reverse vaccinology. The information obtained in this study could be used for further theoretic and experimental explorations on coronavirus infection mechanism and development of medicines for treatment.


Asunto(s)
Betacoronavirus/metabolismo , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Imitación Molecular/fisiología , Dominios y Motivos de Interacción de Proteínas/inmunología , Betacoronavirus/genética , /virología , Infecciones por Coronavirus/genética , Bases de Datos Genéticas , Interacciones Huésped-Patógeno , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/metabolismo , Dominios Proteicos , Dominios y Motivos de Interacción de Proteínas/genética , Proteoma , Virus del SRAS/genética , Virus del SRAS/metabolismo , /metabolismo , Proteínas Virales/metabolismo
6.
Viruses ; 13(1)2020 12 26.
Artículo en Inglés | MEDLINE | ID: covidwho-1079698

RESUMEN

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate these deleterious events by inciting inflammatory and microvascular thrombotic processes. Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein. In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction. Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells. Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process.


Asunto(s)
/metabolismo , Células Endoteliales/metabolismo , Endotelio/metabolismo , /inmunología , Proteína ADAM17/metabolismo , Antivirales/uso terapéutico , Coronavirus , Infecciones por Coronavirus/metabolismo , Células Endoteliales/inmunología , Endotelio/inmunología , Endotelio/virología , Endotelio Vascular/inmunología , Endotelio Vascular/metabolismo , Humanos , Pulmón/metabolismo , Trombosis , Replicación Viral
7.
Sci Rep ; 10(1): 14214, 2020 08 26.
Artículo en Inglés | MEDLINE | ID: covidwho-1065924

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major public health concern. A handful of static structures now provide molecular insights into how SARS-CoV-2 and SARS-CoV interact with its host target, which is the angiotensin converting enzyme 2 (ACE2). Molecular recognition, binding and function are dynamic processes. To evaluate this, multiple 500 ns or 1 µs all-atom molecular dynamics simulations were performed to better understand the structural stability and interfacial interactions between the receptor binding domain of the spike (S) protein of SARS-CoV-2 and SARS-CoV bound to ACE2. Several contacts were observed to form, break and reform in the interface during the simulations. Our results indicate that SARS-CoV-2 and SARS-CoV utilizes unique strategies to achieve stable binding to ACE2. Several differences were observed between the residues of SARS-CoV-2 and SARS-CoV that consistently interacted with ACE2. Notably, a stable salt bridge between Lys417 of SARS-CoV-2 S protein and Asp30 of ACE2 as well as three stable hydrogen bonds between Tyr449, Gln493 and Gln498 of SARS-CoV-2 and Asp38, Glu35 and Lys353 of ACE2 were observed, which were absent in the ACE2-SARS-CoV interface. Some previously reported residues, which were suggested to enhance the binding affinity of SARS-CoV-2, were not observed to form stable interactions in these simulations. Molecular mechanics-generalized Born surface area based free energy of binding was observed to be higher for SARS-CoV-2 in all simulations. Stable binding to the host receptor is crucial for virus entry. Therefore, special consideration should be given to these stable interactions while designing potential drugs and treatment modalities to target or disrupt this interface.


Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/metabolismo , Neumonía Viral/virología , Virus del SRAS/fisiología , Síndrome Respiratorio Agudo Grave/virología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Secuencia Conservada , Interacciones Huésped-Patógeno , Humanos , Modelos Moleculares , Pandemias , Peptidil-Dipeptidasa A/química , Unión Proteica , Conformación Proteica , Glicoproteína de la Espiga del Coronavirus/química
8.
Acta Chim Slov ; 67(3): 949-956, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: covidwho-1060696

RESUMEN

Due to the current spreading of the new disease CoViD-19, the World Health Organization formally declared a world pandemic on March 11, 2020. The present trends indicate that the pandemic will have an enormous clinical and economic impact on population health. Infections are initiated by the transmembrane spike (S) glycoproteins of human coronavirus (hCoV) binding to host receptors. Ongoing research and therapeutic product development are of vital importance for the successful treatment of CoViD-19. To contribute somewhat to the overall effort, herein, single point mutations (SPMs) of the binding site residues in hCoV-OC43 S that recognizes cellular surface components containing 9-O-acetylated sialic acid (9-O-Ac-Sia) are explored using an in silico protein engineering approach, while their effects on the binding of 9-O-Ac-Sia and Hidroxychloroquine (Hcq) are evaluated using molecular docking simulations. Thr31Met and Val84Arg are predicted to be the critical - most likely SPMs in hCoV-OC43 S for the binding of 9-O-Ac-Sia and Hcq, respectively, even though Thr31Met is a very likely SPM in the case of Hcq too. The corresponding modes of interaction indicate a comparable strength of the Thr31Met/9-O-Ac-Sia and Val84Arg/Hcq (or Thr31Met/Hcq) complexes. Given that the binding site is conserved in all CoV S glycoproteins that associate with 9-O-acetyl-sialoglycans, the high hydrophobic affinity of Hcq to hCoV-OC43 S speaks in favor of its ability to competitively inhibit rapid S-mediated virion attachment in high-density receptor environments, but its considerably low specificity to hCoV-OC43 S may be one of the key obstacles in considering the potential of Hcq to become a drug candidate.


Asunto(s)
Infecciones por Coronavirus/virología , Coronavirus Humano OC43/genética , Hidroxicloroquina/metabolismo , Mutación Puntual , Ácidos Siálicos/metabolismo , Glicoproteína de la Espiga del Coronavirus/genética , Sitios de Unión , Infecciones por Coronavirus/metabolismo , Coronavirus Humano OC43/química , Coronavirus Humano OC43/metabolismo , Humanos , Simulación del Acoplamiento Molecular/métodos , Ingeniería de Proteínas , /genética , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo
9.
BMC Bioinformatics ; 22(1): 18, 2021 Jan 07.
Artículo en Inglés | MEDLINE | ID: covidwho-1059737

RESUMEN

BACKGROUND: The ongoing global COVID-19 pandemic is caused by SARS-CoV-2, a novel coronavirus first discovered at the end of 2019. It has led to more than 50 million confirmed cases and more than 1 million deaths across 219 countries as of 11 November 2020, according to WHO statistics. SARS-CoV-2, SARS-CoV, and MERS-CoV are similar. They are highly pathogenic and threaten public health, impair the economy, and inflict long-term impacts on society. No drug or vaccine has been approved as a treatment for these viruses. Efforts to develop antiviral measures have been hampered by the insufficient understanding of how the human body responds to viral infections at the cellular and molecular levels. RESULTS: In this study, journal articles and transcriptomic and proteomic data surveying coronavirus infections were collected. Response genes and proteins were then identified by differential analyses comparing gene/protein levels between infected and control samples. Finally, the H2V database was created to contain the human genes and proteins that respond to SARS-CoV-2, SARS-CoV, and MERS-CoV infection. CONCLUSIONS: H2V provides molecular information about the human response to infection. It can be a powerful tool to discover cellular pathways and processes relevant for viral pathogenesis to identify potential drug targets. It is expected to accelerate the process of antiviral agent development and to inform preparations for potential future coronavirus-related emergencies. The database is available at: http://www.zhounan.org/h2v .


Asunto(s)
/metabolismo , Infecciones por Coronavirus/metabolismo , Bases de Datos Genéticas , Bases de Datos de Proteínas , Síndrome Respiratorio Agudo Grave/metabolismo , Interfaz Usuario-Computador , /genética , /virología , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/fisiología , Proteómica , Virus del SRAS/fisiología , Síndrome Respiratorio Agudo Grave/genética , Síndrome Respiratorio Agudo Grave/patología , Síndrome Respiratorio Agudo Grave/virología
10.
Int J Mol Sci ; 22(3)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: covidwho-1055069

RESUMEN

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel epidemic strain of Betacoronavirus that is responsible for the current viral pandemic, coronavirus disease 2019 (COVID-19), a global health crisis. Other epidemic Betacoronaviruses include the 2003 SARS-CoV-1 and the 2009 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the genomes of which, particularly that of SARS-CoV-1, are similar to that of the 2019 SARS-CoV-2. In this extensive review, we document the most recent information on Coronavirus proteins, with emphasis on the membrane proteins in the Coronaviridae family. We include information on their structures, functions, and participation in pathogenesis. While the shared proteins among the different coronaviruses may vary in structure and function, they all seem to be multifunctional, a common theme interconnecting these viruses. Many transmembrane proteins encoded within the SARS-CoV-2 genome play important roles in the infection cycle while others have functions yet to be understood. We compare the various structural and nonstructural proteins within the Coronaviridae family to elucidate potential overlaps and parallels in function, focusing primarily on the transmembrane proteins and their influences on host membrane arrangements, secretory pathways, cellular growth inhibition, cell death and immune responses during the viral replication cycle. We also offer bioinformatic analyses of potential viroporin activities of the membrane proteins and their sequence similarities to the Envelope (E) protein. In the last major part of the review, we discuss complement, stimulation of inflammation, and immune evasion/suppression that leads to CoV-derived severe disease and mortality. The overall pathogenesis and disease progression of CoVs is put into perspective by indicating several stages in the resulting infection process in which both host and antiviral therapies could be targeted to block the viral cycle. Lastly, we discuss the development of adaptive immunity against various structural proteins, indicating specific vulnerable regions in the proteins. We discuss current CoV vaccine development approaches with purified proteins, attenuated viruses and DNA vaccines.


Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/metabolismo , Proteínas de la Matriz Viral/metabolismo , Animales , Betacoronavirus/genética , Betacoronavirus/inmunología , /metabolismo , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Genoma Viral , Interacciones Huésped-Patógeno , Humanos , Evasión Inmune , Mapas de Interacción de Proteínas , /inmunología , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/inmunología , Internalización del Virus , Replicación Viral
11.
Virology ; 556: 1-8, 2021 04.
Artículo en Inglés | MEDLINE | ID: covidwho-1045103

RESUMEN

Porcine deltacoronavirus (PDCoV) is one of the emerged coronaviruses posing a significant threat to the swine industry. Previous work showed the presence of a viral accessory protein NS6 in PDCoV-infected cells. In this study, we detected the expression of the NS6 protein in small intestinal tissues of PDCoV-infected piglets. In addition, SDS-PAGE and Western blot analysis of sucrose gradient-purified virions showed the presence of a 13-kDa NS6 protein. Further evidences of the presence of NS6 in the PDCoV virions were obtained by immunogold staining of purified virions with anti-NS6 antiserum, and by immunoprecipitation of NS6 from purified virions. Finally, the anti-NS6 antibody was not able to neutralize PDCoV in cultured cells. These data establish for the first time that the accessory protein NS6 is expressed during infection in vivo and incorporated into PDCoV virions.


Asunto(s)
Infecciones por Coronavirus/veterinaria , Enfermedades de los Porcinos/virología , Proteínas no Estructurales Virales/metabolismo , Virión/metabolismo , Animales , Anticuerpos Antivirales/inmunología , Línea Celular , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/virología , Ratones , Conejos , Porcinos , Enfermedades de los Porcinos/metabolismo , Proteínas no Estructurales Virales/inmunología
12.
BMC Biol ; 19(1): 12, 2021 01 22.
Artículo en Inglés | MEDLINE | ID: covidwho-1044598

RESUMEN

BACKGROUND: Pandemics, even more than other medical problems, require swift integration of knowledge. When caused by a new virus, understanding the underlying biology may help finding solutions. In a setting where there are a large number of loosely related projects and initiatives, we need common ground, also known as a "commons." Wikidata, a public knowledge graph aligned with Wikipedia, is such a commons and uses unique identifiers to link knowledge in other knowledge bases. However, Wikidata may not always have the right schema for the urgent questions. In this paper, we address this problem by showing how a data schema required for the integration can be modeled with entity schemas represented by Shape Expressions. RESULTS: As a telling example, we describe the process of aligning resources on the genomes and proteomes of the SARS-CoV-2 virus and related viruses as well as how Shape Expressions can be defined for Wikidata to model the knowledge, helping others studying the SARS-CoV-2 pandemic. How this model can be used to make data between various resources interoperable is demonstrated by integrating data from NCBI (National Center for Biotechnology Information) Taxonomy, NCBI Genes, UniProt, and WikiPathways. Based on that model, a set of automated applications or bots were written for regular updates of these sources in Wikidata and added to a platform for automatically running these updates. CONCLUSIONS: Although this workflow is developed and applied in the context of the COVID-19 pandemic, to demonstrate its broader applicability it was also applied to other human coronaviruses (MERS, SARS, human coronavirus NL63, human coronavirus 229E, human coronavirus HKU1, human coronavirus OC4).


Asunto(s)
/patología , Genómica/métodos , Bases del Conocimiento , Proteómica/métodos , /fisiología , /metabolismo , Coronavirus/genética , Coronavirus/fisiología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Genoma Viral , Humanos , Internet , Pandemias , Proteínas Virales/genética , Proteínas Virales/metabolismo , Flujo de Trabajo
13.
Mol Biol Rep ; 48(2): 1763-1771, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: covidwho-1044134

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to the outbreak of coronavirus disease 2019 (COVID-19), a worldwide epidemic disease affecting increasing number of patients. Although the virus primarily targets respiratory system, cardiovascular involvement has been reported in accumulating studies. In this review, we first describe the cardiac disorders in human with various types of CoV infection, and in animals infected with coronavirus. Particularly, we will focus on the association of cardiovascular disorders upon SARS-CoV-2 infection, and prognostic cardiac biomarkers in COVID-19. Besides, we will discuss the possible mechanisms underlying cardiac injury resulted from SARS-CoV-2 infection including direct myocardial injury caused by viral infection, reduced level of ACE2, and inflammatory response during infection. Improved understandings of cardiac disorders associated with COVID-19 might predict clinical outcome and provide insights into more rational treatment responses in clinical practice.


Asunto(s)
/metabolismo , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/metabolismo , /aislamiento & purificación , Animales , /virología , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/diagnóstico , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Interacciones Huésped-Patógeno , Humanos , Pronóstico , /fisiología
15.
Endocrinol Metab (Seoul) ; 35(2): 197-205, 2020 06.
Artículo en Inglés | MEDLINE | ID: covidwho-1004777

RESUMEN

The world is entering an era of disaster and chaos due to coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. Since its first emergence in December 2019 in Wuhan, China, COVID-19 has swept through Asia and propagated throughout the world to Europe and North America. As of April 13, 1,773,084 people were infected and 111,652 people had died from COVID-19 globally, and new record levels of infection are being reported every day. Based on the data that have been amassed so far, the primary risk factors for a severe disease course or even mortality from COVID-19 are underlying diseases such as diabetes and hypertension. As the global prevalence of diabetes continues to increase, patients with endocrine diseases such as diabetes mellitus and those who are on long-term corticosteroid therapy due to adrenal insufficiency or hypopituitarism are at risk for a poor prognosis of COVID-19. As endocrinologists, we would like to briefly review the current knowledge about the relationship between COVID-19 and endocrine diseases and to discuss what we can do for the safety and health of our patients with endocrine diseases in this globally threatening situation.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/metabolismo , Enfermedades del Sistema Endocrino/epidemiología , Enfermedades del Sistema Endocrino/metabolismo , Endocrinólogos/tendencias , Neumonía Viral/epidemiología , Neumonía Viral/metabolismo , Infecciones por Coronavirus/diagnóstico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/metabolismo , Enfermedades del Sistema Endocrino/diagnóstico , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/metabolismo , Pandemias , Neumonía Viral/diagnóstico , Factores de Riesgo
16.
Pharmacol Res Perspect ; 9(1): e00691, 2021 02.
Artículo en Inglés | MEDLINE | ID: covidwho-996298

RESUMEN

Coronaviruses represent global health threat. In this century, they have already caused two epidemics and one serious pandemic. Although, at present, there are no approved drugs and therapies for the treatment and prevention of human coronaviruses, several agents, FDA-approved, and preclinical, have shown in vitro and/or in vivo antiviral activity. An in-depth analysis of the current situation leads to the identification of several potential drugs that could have an impact on the fight against coronaviruses infections. In this review, we discuss the virology of human coronaviruses highlighting the main biological targets and summarize the current state-of-the-art of possible therapeutic options to inhibit coronaviruses infections. We mostly focus on FDA-approved and preclinical drugs targeting viral conserved elements.


Asunto(s)
/metabolismo , Infecciones por Coronavirus/metabolismo , Coronavirus/metabolismo , Dipeptidil Peptidasa 4/metabolismo , Síndrome Respiratorio Agudo Grave/metabolismo , /antagonistas & inhibidores , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/metabolismo , Antivirales/administración & dosificación , Antivirales/metabolismo , Azoles/administración & dosificación , Azoles/metabolismo , Coronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/metabolismo , Humanos , Naftoquinonas/administración & dosificación , Naftoquinonas/metabolismo , Compuestos de Organoselenio/administración & dosificación , Compuestos de Organoselenio/metabolismo , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico
17.
Ann Med ; 53(1): 227-236, 2021 12.
Artículo en Inglés | MEDLINE | ID: covidwho-990291

RESUMEN

The coronavirus disease-2019 (COVID-19), an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2), has hit the world very hard by affecting millions of people across countries hence posing a major health threat on a global scale. This novel virus is thought to enter and cause infection in its host through the attachment of its structural protein known as the S-glycoprotein to angiotensin-converting enzyme 2 (ACE2). Given the rapid spread of COVID-19 with its consequences globally, it is mandatory that health caregivers and researchers across all disciplines abreast themselves with the potential effects that this novel virus may have on their fields and the medical society at large. During the infection, the cardiovascular system is affected by unknown pathomechanistic processes, hence accounting for an increased prevalence of cardiovascular diseases (CVDs) among COVID-19 patients. As cardiovascular researchers, we are more concerned about the cardiovascular aspect of SARS-CoV-2/COVID-19. Hence, this concise review addresses these aspects where CVD as a risk factor of COVID-19, the prevalence of CVDs in COVID-19, and the potential cardiovascular disorders which may evolve owing to COVID-19 are discussed. A better understanding of these issues will be pivotal to improve cardiovascular health during this SARS-CoV-2/COVID-19 pandemic and beyond.


Asunto(s)
/metabolismo , Infecciones por Coronavirus/metabolismo , Endotelio Vascular/metabolismo , /metabolismo , /fisiopatología , Infecciones por Coronavirus/fisiopatología , Humanos , Sistema Renina-Angiotensina
18.
Microb Pathog ; 150: 104719, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: covidwho-988888

RESUMEN

The recent outbreak of Covid-19 is posing a severe threat to public health globally. Coronaviruses (CoVs) are the largest known group of positive-sense RNA viruses surviving on an extensive number of natural hosts. CoVs are enveloped and non-segmented viruses with a size between 80 and 120 nm. CoV attachment to the surface receptor and its subsequent entrance into cells is mediated by Spike glycoprotein (S). For enhanced CoV entry and successful pathogenesis of CoV, proteolytic processing and receptor-binding act synergistically for induction of large-scale S conformational changes. The shape, size and orientation of receptor-binding domains in viral attachment proteins are well conserved among viruses of different classes that utilize the same receptor. Therefore, investigations unraveling the distribution of cellular receptors with respect to CoV entry, structural aspects of glycoproteins and related conformational changes are highly significant for understanding virus invasion and infection spread. We present the characteristic features of CoV S-Proteins, their significance for CoVs and related receptor binding activities for pathogenesis and viral survival. We are analyzing the novel role of S-protein of CoVs along with their interactive receptors for improving host immunity and decreasing infection spread. This is hoped that presented information will open new ways in tackling coronavirus, especially for the ongoing epidemic.


Asunto(s)
Infecciones por Coronavirus/virología , Coronavirus/fisiología , Glicoproteína de la Espiga del Coronavirus/metabolismo , /metabolismo , Animales , Sitios de Unión , /metabolismo , Coronavirus/genética , Coronavirus/inmunología , Infecciones por Coronavirus/metabolismo , Humanos , Unión Proteica , Conformación Proteica , /fisiología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Internalización del Virus , Replicación Viral
19.
Viruses ; 12(10)2020 09 26.
Artículo en Inglés | MEDLINE | ID: covidwho-982816

RESUMEN

In a short time, the COVID-19 pandemic has left the world with over 25 million cases and staggering death tolls that are still rising. Treatments for SARS-CoV-2 infection are desperately needed as there are currently no approved drug therapies. With limited knowledge of viral mechanisms, a network controllability method of prioritizing existing drugs for repurposing efforts is optimal for quickly moving through the drug approval pipeline using limited, available, virus-specific data. Based on network topology and controllability, 16 proteins involved in translation, cellular transport, cellular stress, and host immune response are predicted as regulators of the SARS-CoV-2 infected cell. Of the 16, eight are prioritized as possible drug targets where two, PVR and SCARB1, are previously unexplored. Known compounds targeting these genes are suggested for viral inhibition study. Prioritized proteins in agreement with previous analysis and viral inhibition studies verify the ability of network controllability to predict biologically relevant candidates.


Asunto(s)
Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Reposicionamiento de Medicamentos/métodos , Neumonía Viral/tratamiento farmacológico , Betacoronavirus/aislamiento & purificación , Betacoronavirus/fisiología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Aprobación de Drogas , Sistemas de Liberación de Medicamentos , Interacciones Huésped-Patógeno , Humanos , Pandemias , Neumonía Viral/metabolismo , Neumonía Viral/virología , Mapas de Interacción de Proteínas/efectos de los fármacos , Receptores Virales/genética , Receptores Virales/metabolismo , Receptores Depuradores de Clase B/metabolismo , Integración Viral
20.
JCI Insight ; 5(11)2020 06 04.
Artículo en Inglés | MEDLINE | ID: covidwho-980226

RESUMEN

In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have the potential to propagate inflammation and microvascular thrombosis - including in the lungs of patients with acute respiratory distress syndrome. We now report that sera from patients with COVID-19 have elevated levels of cell-free DNA, myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (Cit-H3); the latter 2 are specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute-phase reactants, including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.


Asunto(s)
Ácidos Nucleicos Libres de Células/metabolismo , Infecciones por Coronavirus/metabolismo , Trampas Extracelulares/metabolismo , Histonas/metabolismo , Neutrófilos/metabolismo , Peroxidasa/metabolismo , Neumonía Viral/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Citrulinación , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/terapia , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Técnicas In Vitro , L-Lactato Deshidrogenasa/metabolismo , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Pandemias , Recuento de Plaquetas , Neumonía Viral/sangre , Neumonía Viral/terapia , Respiración Artificial , Índice de Severidad de la Enfermedad
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