ABSTRACT
Interferons (IFNs) play a crucial role in the regulation and evolution of host-virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence SARS-CoV-2 infection. We then performed an integrated analysis of genes interacting with SARS-CoV-2, drawing from a selection of 67 large-scale studies, including our own. We identified 28 genes of high relevance in both human genetic studies of COVID-19 patients and functional genetic screens in cell culture, with many related to the IFN pathway. Among these was the IFN-stimulated gene PLSCR1. PLSCR1 did not require IFN induction to restrict SARS-CoV-2 and did not contribute to IFN signaling. Instead, PLSCR1 specifically restricted spike-mediated SARS-CoV-2 entry. The PLSCR1-mediated restriction was alleviated by TMPRSS2 over-expression, suggesting that PLSCR1 primarily restricts the endocytic entry route. In addition, recent SARS-CoV-2 variants have adapted to circumvent the PLSCR1 barrier via currently undetermined mechanisms. Our study contributes to understanding the association between PLSCR1 variants and severe COVID-19 cases reported in a recent GWAS.
Subject(s)
COVID-19ABSTRACT
Despite the development of effective vaccines against SARS-CoV-2, epidemiological control of the virus is still challenging due to slow vaccine rollouts, incomplete vaccine protection to current and emerging variants, and unwillingness to get vaccinated. Therefore, frequent testing of individuals to identify early SARS-CoV-2 infections, contact-tracing and isolation strategies remain crucial to mitigate viral spread. Here, we describe WHotLAMP, a rapid molecular test to detect SARS-CoV-2 in saliva. WHotLAMP is simple to use, highly sensitive (3.6 viral RNA copies per microliter of saliva) and specific, as well as inexpensive, making it ideal for frequent screening. Moreover, WHotLAMP does not require harsh chemicals or specialized equipment and thus can be performed in point-of-care settings, and may also be adapted for resource-limited environments or home use. While applied here to SARS-CoV-2, WHotLAMP can be easily modified to detect other pathogens, making it adaptable for other diagnostic assays, including for use in future outbreaks.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Shortages in N95 filtering facepiece respirators (FFRs) are significant as FFRs are essential for the protection of healthcare professionals and other high-risk groups against Coronavirus Disease of 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2. In response to these shortages during the ongoing COVID-19 pandemic, the Food and Drug Administration issued an Emergency Use Authorization (EUA) permitting FFR decontamination and reuse. However, although industrial decontamination services are available at some large institutions, FFR decontamination is not widely available. Effective FFR decontamination must 1) deactivate the virus; 2) preserve FFR integrity, specifically fit and filtering capability; and 3) be non-toxic and safe. Here we identify and compare at-home methods for heat-based FFR decontamination that meet these requirements, but utilize common household appliances. Our results identify viable protocols for simple and accessible FFR decontamination, while also highlighting methods that may jeopardize FFR integrity and should be avoided.