RESUMEN
Despite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges to researchers aiming to study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with its main host cell receptor, angiotensin-converting enzyme 2 (ACE2), has emerged as a critical focal point for the development of anti-viral therapeutics and vaccines. In this study, we selectively identify and characterize the impact of mutating certain amino acid residues in the RBD of SARS-CoV-2 and in ACE2, by utilizing our recently developed NanoBiT technology-based biosensor as well as pseudotyped-virus infectivity assays. Specifically, we examine the mutational effects on RBD-ACE2 binding ability, efficacy of competitive inhibitors, as well as neutralizing antibody activity. We also look at the implications the mutations may have on virus transmissibility, host susceptibility, and the virus transmission path to humans. These critical determinants of virus-host interactions may provide more effective targets for ongoing vaccines, drug development, and potentially pave the way for determining the genetic variation underlying disease severity.
Asunto(s)
Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/metabolismo , COVID-19/virología , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Secuencia de Aminoácidos , Enzima Convertidora de Angiotensina 2/genética , Anticuerpos Neutralizantes/inmunología , Antivirales/farmacología , Sitios de Unión , COVID-19/inmunología , Células HEK293 , Interacciones Microbiota-Huesped , Humanos , Modelos Moleculares , Mutación , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Receptores Virales/química , Receptores Virales/metabolismo , SARS-CoV-2/efectos de los fármacos , Alineación de Secuencia , Tratamiento Farmacológico de COVID-19RESUMEN
Inflammation is a biological response to the activation of the immune system by various infectious or non-infectious agents, which may lead to tissue damage and various diseases. Gut commensal bacteria maintain a symbiotic relationship with the host and display a critical function in the homeostasis of the host immune system. Disturbance to the gut microbiota leads to immune dysfunction both locally and at distant sites, which causes inflammatory conditions not only in the intestine but also in the other organs such as lungs and brain, and may induce a disease state. Probiotics are well known to reinforce immunity and counteract inflammation by restoring symbiosis within the gut microbiota. As a result, probiotics protect against various diseases, including respiratory infections and neuroinflammatory disorders. A growing body of research supports the beneficial role of probiotics in lung and mental health through modulating the gut-lung and gut-brain axes. In the current paper, we discuss the potential role of probiotics in the treatment of viral respiratory infections, including the COVID-19 disease, as major public health crisis in 2020, and influenza virus infection, as well as treatment of neurological disorders like multiple sclerosis and other mental illnesses.
Asunto(s)
Infecciones por Coronavirus/terapia , Gripe Humana/terapia , Trastornos Mentales/terapia , Esclerosis Múltiple/terapia , Neumonía Viral/terapia , Probióticos/uso terapéutico , Infecciones del Sistema Respiratorio/terapia , Betacoronavirus/efectos de los fármacos , Betacoronavirus/patogenicidad , Betacoronavirus/fisiología , Encéfalo/inmunología , COVID-19 , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/microbiología , Infecciones por Coronavirus/virología , Microbioma Gastrointestinal/inmunología , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/microbiología , Humanos , Inmunomodulación , Gripe Humana/inmunología , Gripe Humana/microbiología , Gripe Humana/virología , Pulmón/inmunología , Trastornos Mentales/inmunología , Trastornos Mentales/microbiología , Consorcios Microbianos/inmunología , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/microbiología , Orthomyxoviridae/efectos de los fármacos , Orthomyxoviridae/patogenicidad , Orthomyxoviridae/fisiología , Pandemias , Neumonía Viral/inmunología , Neumonía Viral/microbiología , Neumonía Viral/virología , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/microbiología , SARS-CoV-2 , Simbiosis/inmunologíaRESUMEN
Inflammation is a biological response to the activation of the immune system by various infectious or non-infectious agents, which may lead to tissue damage and various diseases. Gut commensal bacteria maintain a symbiotic relationship with the host and display a critical function in the homeostasis of the host immune system. Disturbance to the gut microbiota leads to immune dysfunction both locally and at distant sites, which causes inflammatory conditions not only in the intestine but also in the other organs such as lungs and brain, and may induce a disease state. Probiotics are well known to reinforce immunity and counteract inflammation by restoring symbiosis within the gut microbiota. As a result, probiotics protect against various diseases, including respiratory infections and neuroinflammatory disorders. A growing body of research supports the beneficial role of probiotics in lung and mental health through modulating the gut-lung and gut-brain axes. In the current paper, we discuss the potential role of probiotics in the treatment of viral respiratory infections, including the COVID-19 disease, as major public health crisis in 2020, and influenza virus infection, as well as treatment of neurological disorders like multiple sclerosis and other mental illnesses.