RESUMEN
Viruses can be spread from one person to another; therefore, they may cause disorders in many people, sometimes leading to epidemics and even pandemics. New, previously unstudied viruses and some specific mutant or recombinant variants of known viruses constantly appear. An example is a variant of coronaviruses (CoV) causing severe acute respiratory syndrome (SARS), named SARS-CoV-2. Some antiviral drugs, such as remdesivir as well as antiretroviral drugs including darunavir, lopinavir, and ritonavir are suggested to be effective in treating disorders caused by SARS-CoV-2. There are data on the utilization of antiretroviral drugs against SARS-CoV-2. Since there are many studies aimed at the identification of the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) infection and the development of novel therapeutic approaches against HIV-1, we used HIV-1 for our case study to identify possible molecular pathways shared by SARS-CoV-2 and HIV-1. We applied a text and data mining workflow and identified a list of 46 targets, which can be essential for the development of infections caused by SARS-CoV-2 and HIV-1. We show that SARS-CoV-2 and HIV-1 share some molecular pathways involved in inflammation, immune response, cell cycle regulation.
Asunto(s)
Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/metabolismo , Minería de Datos/métodos , Infecciones por VIH/epidemiología , Infecciones por VIH/metabolismo , Interacciones Huésped-Patógeno/inmunología , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/metabolismo , Antiinflamatorios/uso terapéutico , Antígenos de Diferenciación/genética , Antígenos de Diferenciación/inmunología , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , COVID-19 , Proteínas del Sistema Complemento/genética , Proteínas del Sistema Complemento/inmunología , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/inmunología , Bases de Datos Genéticas , Regulación de la Expresión Génica , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , VIH-1/efectos de los fármacos , VIH-1/inmunología , VIH-1/patogenicidad , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/genética , Humanos , Inmunidad Innata/efectos de los fármacos , Factores Inmunológicos/uso terapéutico , Inflamación , Interferones/genética , Interferones/inmunología , Interleucinas/genética , Interleucinas/inmunología , Redes y Vías Metabólicas/efectos de los fármacos , Redes y Vías Metabólicas/genética , Redes y Vías Metabólicas/inmunología , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/inmunología , Proteínas Represoras/genética , Proteínas Represoras/inmunología , SARS-CoV-2 , Transducción de Señal , Receptores Toll-Like/genética , Receptores Toll-Like/inmunología , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/inmunologíaRESUMEN
A weak production of INF-ß along with an exacerbated release of pro-inflammatory cytokines have been reported during infection by the novel SARS-CoV-2 virus. SARS-CoV-2 encodes several proteins able to counteract the host immune system, which is believed to be one of the most important features contributing to the viral pathogenesis and development of a severe clinical picture. Previous reports have demonstrated that SARS-CoV-2 N protein, along with some non-structural and accessory proteins, efficiently suppresses INF-ß production by interacting with RIG-I, an important pattern recognition receptor (PRR) involved in the recognition of pathogen-derived molecules. In the present study, we better characterized the mechanism by which the SARS-CoV-2 N counteracts INF-ß secretion and affects RIG-I signaling pathways. In detail, when the N protein was ectopically expressed, we noted a marked decrease in TRIM25-mediated RIG-I activation. The capability of the N protein to bind to, and probably mask, TRIM25 could be the consequence of its antagonistic activity. Furthermore, this interaction occurred at the SPRY domain of TRIM25, harboring the RNA-binding activity necessary for TRIM25 self-activation. Here, we describe new findings regarding the interplay between SARS-CoV-2 and the IFN system, filling some gaps for a better understanding of the molecular mechanisms affecting the innate immune response in COVID-19.
Asunto(s)
COVID-19/inmunología , Proteínas de la Nucleocápside de Coronavirus/inmunología , Proteína 58 DEAD Box/inmunología , Receptores Inmunológicos/inmunología , SARS-CoV-2/inmunología , Factores de Transcripción/inmunología , Proteínas de Motivos Tripartitos/inmunología , Ubiquitina-Proteína Ligasas/inmunología , COVID-19/genética , COVID-19/virología , Proteínas de la Nucleocápside de Coronavirus/genética , Proteína 58 DEAD Box/genética , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno , Humanos , Inmunidad Innata , Interferón beta/genética , Interferón beta/inmunología , Regiones Promotoras Genéticas , Receptores Inmunológicos/genética , SARS-CoV-2/genética , Transducción de Señal , Factores de Transcripción/genética , Proteínas de Motivos Tripartitos/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
INTRODUCTION: The tripartite motif (TRIM) plays various roles in pathological and physiological functions, including neurological diseases, genetic disorders, carcinogenesis, innate immune signaling, and antiviral activity. TRIM56 is a cytoplasmic protein whose expression is stimulated by type I interferon and may function as an antiviral agent. Here, the authors conducted a systematic search on papers that reported antiviral effects of TRIM56. AREAS COVERED: The authors conducted a comprehensive search of the PubMed database without time or language limitation, after using the Medical Subject Headings (MeSH) Database terms. Initially, a structured search and full article review yielded 31 papers. Relevant original and review articles on TRIM56 were included. The reference lists were then reviewed, and the cited articles were added. Expert opinion: TRIM56 has been shown to have direct antiviral actions against positive-sense single-stranded RNA viruses from the families Flaviviridae, Coronaviridae, and Retroviridae. Moreover, it may be effective against negative-sense single-strand RNA viruses from the families Paramyxoviridae and Orthomyxoviridae, as well as a DNA virus, Herpes simplex virus 1 (HSV-1). These studies could suggest the potential of a TRIM56-based antiviral against COVID-19 from the family Coronaviridae, containing single-stranded positive-sense RNA genome. However, its efficacy and antiviral mechanisms need to be further examined.