RESUMEN
An outbreak of coronavirus disease 2019 (COVID-19)1-3, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)4, has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Neumonía Viral/inmunología , Neumonía Viral/virología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Enzima Convertidora de Angiotensina 2 , Animales , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/farmacología , Anticuerpos Antivirales/química , Anticuerpos Antivirales/farmacología , Betacoronavirus/química , Unión Competitiva , COVID-19 , Línea Celular , Chlorocebus aethiops , Cristalización , Cristalografía por Rayos X , Femenino , Humanos , Técnicas In Vitro , Macaca mulatta/inmunología , Macaca mulatta/virología , Masculino , Modelos Moleculares , Pruebas de Neutralización , Pandemias , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/metabolismo , Unión Proteica/efectos de los fármacos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Glicoproteína de la Espiga del Coronavirus/metabolismo , Células Vero , Carga Viral/inmunologíaRESUMEN
This study used electroencephalogram measurements to investigate the effects of aging on oscillatory theta modulation during an audiovisual discrimination task. By a wavelet-based time-frequency analysis, age-related theta oscillation response differences were observed within a relatively restricted time range (0-500 ms) over frontal-central regions. Older adults showed stronger theta spectral power during visual and audiovisual stimuli in the left frontal regions; however, young adults showed stronger theta spectral power during auditory and audiovisual stimuli in the central regions. These findings suggest that multisensory oscillatory theta responses differ according to age, which further proves that the left frontal regions play an important role in audiovisual integration.
Asunto(s)
Envejecimiento/fisiología , Percepción Auditiva/fisiología , Lóbulo Frontal/fisiología , Ritmo Teta/fisiología , Percepción Visual/fisiología , Estimulación Acústica , Adulto , Anciano , Análisis de Varianza , Mapeo Encefálico , Electroencefalografía , Lateralidad Funcional/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Tiempo de Reacción/fisiología , Adulto JovenRESUMEN
Recent studies have attempted to demonstrate the importance of the characteristics of directional cues and observers' traits in attentional orienting. This study investigated how attentional orienting is influenced by target processing. Two experiments showed the critical role played by target processing in attentional orienting that relies on eye-gaze and arrow cues. In Experiment 1, stronger attentional orienting was observed under the object-target condition compared with the scrambled-display condition, irrespective of whether gaze or arrow cues were used. The results indicated that meaningful targets produced stronger attentional orienting than did meaningless targets, regardless of the social characteristics of the target. Experiment 2, which investigated whether attentional orienting was influenced by differences in the meaningfulness of targets regardless of their perceptual features, used participants' own faces and the faces of others as target stimuli; one's own face is typically more meaningful than the face of another. The results showed stronger attentional orienting in response to one's own face than in response to another's face under both gaze and arrow conditions. These findings suggest that the use of task-irrelevant meaningful information as targets may be effective in enhancing attention, regardless of perceptual features.