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Cell Rep ; 37(3): 109869, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1517084


The dramatically expanding coronavirus disease 2019 (COVID-19) needs multiple effective countermeasures. Neutralizing nanobodies (Nbs) are a potential therapeutic strategy for treating COVID-19. Here, we characterize several receptor binding domain (RBD)-specific Nbs isolated from an Nb library derived from an alpaca immunized with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S); among them, three Nbs exhibit picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and circulating SARS-CoV-2 variants. To improve their efficacy, various configurations of Nbs are engineered. Nb15-NbH-Nb15, a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb15-NbH-Nb15 exhibits single-digit ng/ml neutralization potency against the wild-type and Delta variants of SARS-CoV-2 with a long half-life in vivo. In addition, we show that intranasal administration of Nb15-NbH-Nb15 provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb15-NbH-Nb15 is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration.

Administration, Intranasal , Angiotensin-Converting Enzyme 2/immunology , Antibodies, Bispecific/immunology , COVID-19/immunology , SARS-CoV-2 , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Neutralizing , Antibodies, Viral/immunology , Camelids, New World , Epitopes/chemistry , Female , Humans , Kinetics , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neutralization Tests , Protein Binding , Protein Domains , Protein Engineering/methods , Serum Albumin, Human/chemistry , Single-Domain Antibodies , Spike Glycoprotein, Coronavirus/immunology
Front Psychiatry ; 12: 685964, 2021.
Article in English | MEDLINE | ID: covidwho-1292120


The COVID-19 (coronavirus disease 2019) pandemic has dramatically changed our daily lives and activities, including those originally intended to serve for leisure and pleasure. Drinking and online gaming became coping behaviors used to rescue ourselves from the stress and restricted lifestyle during the COVID-19 pandemic. However, frequent drinking and gaming can result in the pathological consequences of addiction. Those affected use the stimuli not to obtain pleasure, but rather to avoid the displeasure induced by stress and previous use, often unsuccessfully. This review aims to provide an overview of recent longitudinal cohort studies on alcohol and gaming use during the COVID-19 pandemic, as well as to analyze how the pandemic has affected alcohol and gaming use. There was a substantial risk of alcohol and online gaming overuse during the lockdown, which may depend on the pandemic's duration or overuse patterns. Previous studies have shown that increased alcohol consumption and online gaming are associated with heightened stress and anxiety levels caused by social isolation/quarantine. Over time, frequent or excessive alcohol consumption and gaming could lead to an increased risk of more serious mental health problems. Every effort should be made to mitigate mental health problems and ensure adequate adaptation to these exceptional circumstances. Therefore, it would be helpful to encourage physical activity, social interaction, and collaboration to facilitate psychological and physical health.