Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that is a serious global health problem. Evasion of IFN-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in their host. In this study, we show that SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of IFN-stimulated genes (ISGs). Our results demonstrate that the viral accessory protein Orf6 exerts this anti-IFN activity. We found that SARS-CoV-2 Orf6 localizes at the nuclear pore complex (NPC) and directly interacts with Nup98-Rae1 via its C-terminal domain to impair docking of cargo-receptor (karyopherin/importin) complex and disrupt nuclear import. In addition, we show that a methionine-to-arginine substitution at residue 58 impairs Orf6 binding to the Nup98-Rae1 complex and abolishes its IFN antagonistic function. All together our data unravel a mechanism of viral antagonism in which a virus hijacks the Nup98-Rae1 complex to overcome the antiviral action of IFN.

Brain, Behavior, and Immunity xxx (xxxx) xxx-xxx 0889-1591/

The discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the outbreak of coronavirus disease 2019 are causing public health emergency. A handful of literatures have summarized its clinical and radiologic features, whereas therapies for COVID-19 are rather limited. In order to evaluate the efficacy of convalescent plasma therapy in COVID-19 patients, we did this timely descriptive study. 6 laboratory confirmed COVID-19 patients were enrolled and received the transfusion of ABO-compatible convalescent plasma.The efficacy of this intervention was determined by the alleviation of symptoms, changes in radiologic abnormalities and laboratory tests. No obvious adverse effect observed during the treatment. Transfusion of convalescent plasma led to a resolution of ground glass opacities (GGOs) and consolidation in patient #1, #2, #3, #4 and #6. In patient #1 and #5 who presented with SARS-CoV-2 in throat This article is protected by copyright. All rights reserved. Accepted Articleswab, convalescent plasma therapy elicited an elimination of virus. Serologic analysis indicated an immediate increase in anti-SARS-CoV-2 antibody titers in patient #2 and #3, but not in patient #1. This study indicates that convalescent plasma therapy is effective and specific for COVID-19. This intervention has a special significance for eliminating SARS-CoV-2 and is believed to be a promising state-of-art therapy during COVID-19 pandemic crisis.