The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation.

Viral proteins localize within subcellular compartments to subvert host machinery and promote pathogenesis. To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 SARS-CoV-2 viral proteins using proximity proteomics. This identified viral proteins at specific intracellular locations, such as association of accessary proteins with intracellular membranes, and projected SARS-CoV-2 impacts on innate immune signaling, ER-Golgi transport, and protein translation. It identified viral protein adjacency to specific host proteins whose regulatory variants are linked to COVID-19 severity, including the TRIM4 interferon signaling regulator which was found proximal to the SARS-CoV-2 M protein. Viral NSP1 protein adjacency to the EIF3 complex was associated with inhibited host protein translation whereas ORF6 localization with MAVS was associated with inhibited RIG-I 2CARD-mediated IFNB1 promoter activation. Quantitative proteomics identified candidate host targets for the NSP5 protease, with specific functional cleavage sequences in host proteins CWC22 and FANCD2. This data resource identifies host factors proximal to viral proteins in living human cells and nominates pathogenic mechanisms employed by SARS-CoV-2.

Global survey-based assessment of lifestyle changes during the COVID-19 pandemic.

Along with the major impact on public health, the COVID-19 outbreak has caused unprecedented concerns ranging from sudden loss of employment to mental stress and anxiety. We implemented a survey-based data collection platform to characterize how the COVID-19 pandemic has affected the socio-economic, physical and mental health conditions of individuals. We focused on three broad areas, namely, changes in social interaction during home confinement, economic impact and their health status. We identified a substantial increase in virtual interaction among individuals, which might be a way to alleviate the sudden unprecedented mental health burden, exacerbated by general awareness about viral infections or other manifestations associated with them. The majority of participants (85%) lived with one or more companions and unemployment issues did not affect 91% of the total survey takers, which was one of the crucial consequences of the pandemic. Nevertheless, measures such as an increased frequency of technology-aided distant social interaction, focus on physical fitness and leisure activities were adopted as coping mechanisms during this period of home isolation. Collectively, these metrics provide a succinct and informative summary of the socio-economic and health impact of the COVID-19 pandemic on the individuals. Findings from our study reflect that continuous surveillance of the psychological consequences for outbreaks should become routine as part of preparedness efforts worldwide. Given the limitations of analyzing the large number of variables, we have made the raw data publicly available on the OMF ME/CFS Data Center server to facilitate further analyses (https://igenomed.stanford.edu/dataset/survey-study-on-lifestyle-changes-during-covid-19-pandemic).