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4.
Iran J Allergy Asthma Immunol ; 19(5): 456-470, 2020 Oct 18.
Artículo en Inglés | MEDLINE | ID: covidwho-1068112

RESUMEN

The new coronavirus, known as "SARS-CoV-2"; is the cause of one of the most prevalent infectious viral diseases that was recently announced pandemic by the world health organization. Ongoing research in the fields of prevention, management, and therapy establishes a functional scaffold for clinics during the time of crisis. To obtain this goal, it is necessary that all pathophysiologic aspects of COVID-19 from infection to predisposing backgrounds of infection be identified, so that all the ambiguities of researchers regarding transmission mechanisms, variable clinical manifestation, and therapeutic response can be solved. Here, we firstly discuss about the homology screening between nCoV-2019 and beta-coronavirus family using phylogenetic analyses. Secondly, we analyzed the viral motifs to show that viral entry into the host cells requires a primary activation step performed by FURIN and FURIN-like-mediated enzymatic cleavage on the structural glycoprotein. The cleavage increases viral performance by 1000 folds. We then present a comprehensive view on host cells and the significance of gene variants affecting activation enzymes, supportive entry, and spread mechanisms in humans including renin-angiotensin-aldosterone system (RAAS) a pathway results in certain phenotypes or exacerbate infection-related phenotypes in different organs, hence causes variable clinical manifestations. This is followed by discussing about the importance of personalized medicine in nCoV-2019 exposure. Moreover, chemical drugs prescribed for individuals affected with COVID-19, as well as genes involved in drug transport and metabolisms are reviewed as a prelude to drug response. Finally, we suggest some therapeutic approaches developed based on new methods and technology such as anti-sense therapy and antibodies.


Asunto(s)
/genética , Furina/genética , Glicoproteína de la Espiga del Coronavirus/genética , Proteína ADAM17/genética , Proteína ADAM17/metabolismo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Betacoronavirus/genética , /fisiopatología , Inhibidores Enzimáticos/uso terapéutico , Furina/metabolismo , Predisposición Genética a la Enfermedad , Genoma Humano , Genoma Viral , Humanos , Hidroxicloroquina/uso terapéutico , Filogenia , Medicina de Precisión , /metabolismo , Sistema Renina-Angiotensina/genética , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Internalización del Virus
5.
Science ; 371(6530): 735-741, 2021 02 12.
Artículo en Inglés | MEDLINE | ID: covidwho-1066809

RESUMEN

Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-related emergent zoonotic coronaviruses is urgently needed. We made homotypic nanoparticles displaying the receptor binding domain (RBD) of SARS-CoV-2 or co-displaying SARS-CoV-2 RBD along with RBDs from animal betacoronaviruses that represent threats to humans (mosaic nanoparticles with four to eight distinct RBDs). Mice immunized with RBD nanoparticles, but not soluble antigen, elicited cross-reactive binding and neutralization responses. Mosaic RBD nanoparticles elicited antibodies with superior cross-reactive recognition of heterologous RBDs relative to sera from immunizations with homotypic SARS-CoV-2-RBD nanoparticles or COVID-19 convalescent human plasmas. Moreover, after priming, sera from mosaic RBD-immunized mice neutralized heterologous pseudotyped coronaviruses as well as or better than sera from homotypic SARS-CoV-2-RBD nanoparticle immunizations, demonstrating no loss of immunogenicity against particular RBDs resulting from co-display. A single immunization with mosaic RBD nanoparticles provides a potential strategy to simultaneously protect against SARS-CoV-2 and emerging zoonotic coronaviruses.


Asunto(s)
Anticuerpos Antivirales/inmunología , Betacoronavirus/inmunología , Nanopartículas , Glicoproteína de la Espiga del Coronavirus/inmunología , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Infecciones por Coronavirus/inmunología , Reacciones Cruzadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Sueros Inmunes/inmunología , Inmunización , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Ratones , Ratones Endogámicos BALB C , Pruebas de Neutralización , Dominios Proteicos , Receptores de Antígenos de Linfocitos B/inmunología , Glicoproteína de la Espiga del Coronavirus/química , /virología
6.
Viruses ; 13(2)2021 02 03.
Artículo en Inglés | MEDLINE | ID: covidwho-1060766

RESUMEN

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG's antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.


Asunto(s)
Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Coronavirus Humano OC43/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Tapsigargina/farmacología , Animales , Antivirales/uso terapéutico , Betacoronavirus/fisiología , Línea Celular , Línea Celular Tumoral , Células Cultivadas , Coronavirus Humano OC43/fisiología , Estrés del Retículo Endoplásmico , Humanos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Ratones , Pruebas de Sensibilidad Microbiana , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/virología , Virus Sincitial Respiratorio Humano/fisiología , Ribavirina/farmacología , Tapsigargina/uso terapéutico , Replicación Viral/efectos de los fármacos
7.
Cells ; 10(2)2021 02 02.
Artículo en Inglés | MEDLINE | ID: covidwho-1060037

RESUMEN

Many viruses disrupt host gene expression by degrading host mRNAs and/or manipulating translation activities to create a cellular environment favorable for viral replication. Often, virus-induced suppression of host gene expression, including those involved in antiviral responses, contributes to viral pathogenicity. Accordingly, clarifying the mechanisms of virus-induced disruption of host gene expression is important for understanding virus-host cell interactions and virus pathogenesis. Three highly pathogenic human coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and SARS-CoV-2, have emerged in the past two decades. All of them encode nonstructural protein 1 (nsp1) in their genomes. Nsp1 of SARS-CoV and MERS-CoV exhibit common biological functions for inducing endonucleolytic cleavage of host mRNAs and inhibition of host translation, while viral mRNAs evade the nsp1-induced mRNA cleavage. SARS-CoV nsp1 is a major pathogenic determinant for this virus, supporting the notion that a viral protein that suppresses host gene expression can be a virulence factor, and further suggesting the possibility that SARS-CoV-2 nsp1, which has high amino acid identity with SARS-CoV nsp1, may serve as a major virulence factor. This review summarizes the gene expression suppression functions of nsp1 of CoVs, with a primary focus on SARS-CoV nsp1 and MERS-CoV nsp1.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/virología , Proteínas no Estructurales Virales/fisiología , Animales , Betacoronavirus/patogenicidad , Betacoronavirus/fisiología , Regulación de la Expresión Génica , Interacciones Microbiota-Huesped , Humanos , Ratones , ARN Mensajero/genética , Replicación Viral
8.
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
9.
Science ; 371(6531): 823-829, 2021 02 19.
Artículo en Inglés | MEDLINE | ID: covidwho-1048643

RESUMEN

The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope that overlaps the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate against clade 1 sarbecoviruses.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Betacoronavirus/inmunología , Anticuerpos ampliamente neutralizantes/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , /metabolismo , Animales , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/metabolismo , Anticuerpos Antivirales/genética , Anticuerpos Antivirales/metabolismo , Afinidad de Anticuerpos , Sitios de Unión , Sitios de Unión de Anticuerpos , Anticuerpos ampliamente neutralizantes/genética , Anticuerpos ampliamente neutralizantes/metabolismo , /terapia , Técnicas de Visualización de Superficie Celular , Evolución Molecular Dirigida , Epítopos/inmunología , Humanos , Inmunización Pasiva , Fragmentos Fc de Inmunoglobulinas/inmunología , Ratones Endogámicos BALB C , Dominios Proteicos , Ingeniería de Proteínas , Virus del SRAS/inmunología , Síndrome Respiratorio Agudo Grave/inmunología , Síndrome Respiratorio Agudo Grave/prevención & control , Síndrome Respiratorio Agudo Grave/terapia , Glicoproteína de la Espiga del Coronavirus/metabolismo
10.
J Exp Med ; 218(3)2021 03 01.
Artículo en Inglés | MEDLINE | ID: covidwho-1044017

RESUMEN

SARS-CoV-2, the causative agent of COVID-19, has been responsible for over 42 million infections and 1 million deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here, we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a Syrian hamster model of SARS-CoV-2 and in a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). Antibody combinations were effective for prevention and in therapy when administered early. However, in vitro antibody neutralization potency did not uniformly correlate with in vivo protection, and some hu-mAbs were more protective in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors contributes to optimal protection against SARS-CoV-2 MA. The data indicate that intact effector function can affect hu-mAb protective activity and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Betacoronavirus/inmunología , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Animales , Anticuerpos Monoclonales de Origen Murino/inmunología , Anticuerpos Monoclonales de Origen Murino/farmacología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/farmacología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/farmacología , Línea Celular , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/terapia , Femenino , Humanos , Mesocricetus , Ratones , Ratones Endogámicos BALB C , Neumonía Viral/inmunología , Neumonía Viral/terapia
13.
Ann Intern Med ; 174(1): JC2, 2021 01.
Artículo en Inglés | MEDLINE | ID: covidwho-1034497

RESUMEN

SOURCE CITATION: Lamontagne F, Agoritsas T, Macdonald H, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020;370:m3379. 32887691.


Asunto(s)
Corticoesteroides/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Betacoronavirus , Enfermedad Crítica , Humanos , Pandemias , Organización Mundial de la Salud
15.
Bratisl Lek Listy ; 121(11): 775-778, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-1034642

RESUMEN

COVID-19 ‒ a coronavirus disease, affected almost all countries in the world. It is a new virus disease, nobody has prior immunity to it, human population is prone to infections. In March 11 2020, WHO declared the pandemic status. The main symptoms include: fever, dry cough and fatigue. Virus proteins need mitochondrial energy for their own survival and replication. Upon viral infections, mitochondrial dynamics and metabolism can be modulated, which can influence the energy production in the host cells. Coenzyme Q10 is an integral component of mitochondrial respiratory chain and the key component of mitochondrial ATP production. The exact pathobiochemical mechanism of the disease is unknown. Modulated mitochondrial dynamics and metabolism with lower CoQ10 levels in viral infections leads us to the hypothesis that one of the main pathobiochemical effects of SARS-Cov-2 virus could be mitochondrial bioenergetics dysfunction with CoQ10 deficit leading to the reduction of its endogenous biosynthesis. The mechanism might be virus induced oxidative stress causing a mutation of one or more of the nine COQ genes, resulting in primary CoQ10 deficiency. New perspective for patients with COVID-19 may be supportive targeting therapy with coenzyme Q10 to increase the energy production, immunity and decrease oxidative stress (Fig. 1, Ref. 51). Keywords: COVID-19, virus, mitochondrial bioenergetics, coenzyme Q10, oxidative stress.


Asunto(s)
Infecciones por Coronavirus/enzimología , Metabolismo Energético , Mitocondrias/enzimología , Neumonía Viral/enzimología , Ubiquinona/análogos & derivados , Betacoronavirus , Humanos , Pandemias , Ubiquinona/genética
16.
Bratisl Lek Listy ; 121(11): 786-788, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-1034641

RESUMEN

Our understanding of the mechanisms responsible for death of aged people from Covid-19 became one of the major concerns of these days. Glucose-6-phosphate dehydrogenase (G6PD) enhances the normal senescence and accelerates the precocious removal of chronologically young, yet biologically aged cells. Thus, its deficiency is associated with an increase in the cellular oxidative stress. Accumulating evidence showed that oxidative stress has a fundamental role in several age-related diseases. Nowadays, Covid-19 is considered a serious health problem worldwide. The host cellular environment is the key determinant of pathogen Infectivity. Most respiratory viral infections have a strong association with Glucose-6-phosphate dehydrogenase. Unfortunately, this enzyme deficiency markedly decreases with aging what is involved in increasing of the morbidity rate. The aim of this mini review was to shed more light on the role of G6PD deficiency in aged people infected with Covid-19 (Ref. 20). Keywords: GSPD, Covid-19, elderly people.


Asunto(s)
Infecciones por Coronavirus/enzimología , Deficiencia de Glucosafosfato Deshidrogenasa , Neumonía Viral/enzimología , Anciano , Betacoronavirus , Glucosafosfato Deshidrogenasa , Deficiencia de Glucosafosfato Deshidrogenasa/epidemiología , Humanos , Pandemias
17.
Jpn J Infect Dis ; 73(5): 377-380, 2020 Sep 24.
Artículo en Inglés | MEDLINE | ID: covidwho-1034439

RESUMEN

Coronavirus disease 2019 (COVID-19) is a severe infectious disease of the respiratory tract caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2, and has a high mortality rate. The disease emerged from Wuhan, China, in late 2019, and spread to Japan, including Hokkaido, in January 2020. In February 2020, 3 children were diagnosed with COVID-19 in Furano, Hokkaido, Japan. During this period, influenza and human metapneumovirus infections were prevalent among children in the Furano region. Two of the 3 patients experienced co-infection with other respiratory viruses, including influenza virus A or human metapneumovirus. To the authors' knowledge, the cases described in the present report were the first pediatric patients with COVID-19 in Japan. In children with COVID-19, the possibility of co-infection with other respiratory pathogens should be considered.


Asunto(s)
Coinfección/diagnóstico , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , Infecciones del Sistema Respiratorio/diagnóstico , Betacoronavirus/aislamiento & purificación , Niño , Preescolar , Coinfección/patología , Coinfección/virología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Humanos , Japón/epidemiología , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Pandemias , Neumonía Viral/patología , Neumonía Viral/virología , Infecciones del Sistema Respiratorio/patología , Infecciones del Sistema Respiratorio/virología
18.
Rev. enferm. UERJ ; 28: e50470, jan.-dez. 2020.
Artículo en Inglés, Portugués | LILACS (Américas) | ID: covidwho-1029688

RESUMEN

Objetivo: analisar casos acumulados da COVID-19 em Brasil, Espanha, Itália, China e EUA. Métodos: estudo ecológico, com uso de dados secundários. Realizou-se série temporal de casos cumulativos de COVID-19 por 28 dias, após o 100º caso confirmado de cada país (baseado nas estatísticas do Worldometer 2020). Modelos de tendência linear, exponencial, potencial e logaritmo foram testados, sendo escolhido o melhor coeficiente de determinação (R²). No Brasil, a linha de tendência foi segmentada em 1º-14º dia e 15º-28º dia. Resultados: no 100º dia, os EUA possuíam maior número de casos e o Brasil, o menor. Houve linha de tendência em sua maioria exponencial, com maior velocidade de crescimento nos EUA. No Brasil, houve tendência de crescimento mais lento no segundo período. Conclusão: as linhas de tendência calculadas demonstraram pior prognóstico para os EUA. No Brasil, o crescimento do número cumulativo de casos foi mais lento na no segundo período do estudo.


Objective: to examine cumulative cases of COVID-19 in Brazil, Spain, Italy, China, and USA. Method: in this ecological study, secondary data were used to produce time series of cumulative cases of COVID-19 over 28 days after the 100th case confirmed in each country (from Worldometer 2020 statistics). Linear, exponential, potential and logarithmic trend models were tested, and the best coefficient of determination (R²) was chosen. In Brazil, the trend line was segmented into days 1-14 and 15-28. Results: on day 100, the USA had the highest number of cases and Brazil, the lowest. The trend lines were mostly exponential, with highest growth rate in the USA. In Brazil, the growth trend was slower in the second period. Conclusion: the calculated trend lines showed a worse prognosis for the USA. In Brazil, the cumulative number of cases grew more slowly in the second period of the study.


Objetivo: examinar casos acumulados de COVID-19 en Brasil, España, Italia, China y Estados Unidos. Método: en este estudio ecológico, se utilizaron datos secundarios para producir series de tiempo de casos acumulados de COVID-19 durante 28 días después del 100o caso confirmado en cada país (de las estadísticas del Worldometer 2020). Se probaron modelos de tendencia lineal, exponencial, potencial y logarítmica y se eligió el mejor coeficiente de determinación (R²). En Brasil, la línea de tendencia se segmentó en los días 1-14 y 15-28. Resultados: el día 100, EE.UU. tuvo el mayor número de casos y Brasil, el menor. Las líneas de tendencia fueron en su mayoría exponenciales, con la tasa de crecimiento más alta en los EE. UU. En Brasil, la tendencia de crecimiento fue más lenta en el segundo período. Conclusión: las líneas de tendencia calculadas mostraron un peor pronóstico para EE. UU. En Brasil, el número acumulado de casos creció más lentamente en el segundo período del estudio.


Asunto(s)
Humanos , Infecciones por Coronavirus/epidemiología , Betacoronavirus , España/epidemiología , Estados Unidos/epidemiología , Brasil/epidemiología , China/epidemiología , Estudios de Series Temporales , Estudios Ecológicos , Italia/epidemiología
19.
Cell ; 182(4): 828-842.e16, 2020 08 20.
Artículo en Inglés | MEDLINE | ID: covidwho-1027977

RESUMEN

Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.


Asunto(s)
Anticuerpos Neutralizantes/química , Betacoronavirus/química , Infecciones por Coronavirus/inmunología , Fragmentos Fab de Inmunoglobulinas/química , Inmunoglobulina G/química , Neumonía Viral/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/aislamiento & purificación , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/aislamiento & purificación , Betacoronavirus/inmunología , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/terapia , Reacciones Cruzadas , Microscopía por Crioelectrón , Mapeo Epitopo , Epítopos , Humanos , Inmunización Pasiva , Fragmentos Fab de Inmunoglobulinas/sangre , Fragmentos Fab de Inmunoglobulinas/aislamiento & purificación , Fragmentos Fab de Inmunoglobulinas/ultraestructura , Inmunoglobulina G/sangre , Inmunoglobulina G/aislamiento & purificación , Inmunoglobulina G/ultraestructura , Coronavirus del Síndrome Respiratorio de Oriente Medio/química , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Modelos Moleculares , Pandemias , Neumonía Viral/sangre , Virus del SRAS/química , Virus del SRAS/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología
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