Vedelmathews1498

To predict the tropism of human coronaviruses, we profile 28 SCARFs using scRNA-seq data from a wide range of healthy human tissues. SCARFs include cellular factors both facilitating and restricting viral entry. Among adult organs, enterocytes and goblet cells of small intestine and colon, kidney proximal tubule cells, and gallbladder basal cells appear permissive to SARS-CoV-2, consistent with clinical data. Our analysis also suggests alternate entry paths for SARS-CoV-2 infection of the lung, CNS, and heart. We predict spermatogonial cells and prostate endocrine cells, but not ovarian cells, are highly permissive to SARS-CoV-2, suggesting male-specific vulnerabilities. Early embryonic and placental development show a moderate risk of infection. The nasal epithelium is characterized by high expression of both promoting and restricting factors and a potential age-dependent shift in SCARF expression. Lastly, SCARF expression appears broadly conserved across primate organs examined. Our study establishes an important resource for investigations of coronavirus pathology. Funding M.S. is supported by a Presidential Postdoctoral Fellowship from Cornell University. V.B. is supported by a Career Development Fellowship at DZNE Tuebingen. Work on host-virus interactions in the Feschotte lab is funded by R35 GM122550 from the National Institutes of Health. Conflict of Interest The authors declare that there is no conflict of interest.The Latin population in the United States has received relatively little attention despite their vulnerability to COVID-19 during the current pandemic. On Monday, May 4, 2020, the City of El Paso recorded 1,029 cases and 22 deaths. With rising rates of infection and the recent resignation of the city's Public Health Director, El Paso and the region must take proactive precautions to suppress the spread of the virus. To assess the possible impact of COVID-19 in El Paso, we constructed a risk assessment about the populations that could be at higher risk. To do this, we used detailed survey data on health from a sample of 1,152 Hispanic individuals that was gathered with the support of NIH in 2011. To understand how COVID-19 may impact the Latin residents of El Paso, we analyzed risk factors associated with the virus on their own as well as interacting with each other.Antibody-based interventions against SARS-CoV-2 could limit morbidity, mortality, and possibly disrupt epidemic transmission. An anticipated correlate of such countermeasures is the level of neutralizing antibodies against the SARS-CoV-2 spike protein, yet there is no consensus as to which assay should be used for such measurements. ASK inhibitor Using an infectious molecular clone of vesicular stomatitis virus (VSV) that expresses eGFP as a marker of infection, we replaced the glycoprotein gene (G) with the spike protein of SARS-CoV-2 (VSV-eGFP-SARS-CoV-2) and developed a high-throughput imaging-based neutralization assay at biosafety level 2. We also developed a focus reduction neutralization test with a clinical isolate of SARS-CoV-2 at biosafety level 3. We compared the neutralizing activities of monoclonal and polyclonal antibody preparations, as well as ACE2-Fc soluble decoy protein in both assays and find an exceptionally high degree of concordance. The two assays will help define correlates of protection for antiboval This study was approved by the Mayo Clinic Institutional Review Board.ACE2, in concert with the protease TMPRSS2, binds the novel coronavirus SARS-CoV-2 and facilitates its cellular entry. The ACE2 gene is expressed in SARS-CoV-2 target cells, including Type II Pneumocytes (Ziegler, 2020), and is activated by interferons. Viral RNA was also detected in breast milk (Wu et al., 2020), raising the possibility that ACE2 expression is under the control of cytokines through the JAK-STAT pathway. Here we show that Ace2 expression in mammary tissue is induced during pregnancy and lactation, which coincides with the establishment of a candidate enhancer. The prolactin-activated transcription factor STAT5 binds to tandem sites that coincide with activating histone enhancer marks and additional transcription components. The presence of pan JAK-STAT components in mammary alveolar cells and in Type II Pneumocytes combined with the autoregulation of both STAT1 and STAT5 suggests a prominent role of cytokine signaling pathways in cells targeted by SARS-CoV-2. Funding This work was supported by the Intramural Research Program (IRP) of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)and utilized the computational resources of the NIH HPC Biowulf cluster (http//hpc.nih.gov) Declaration of Interest The authors declare not competing interests.COVID-19 (Coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the pathophysiology of this deadly virus is complex and largely unknown, we employ a network biology-fueled approach and integrate multiomics data pertaining to lung epithelial cells-specific co-expression network and human interactome to generate Calu-3-specific human-SARS-CoV-2 Interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 target central nodes of host-viral network that participate in core functional pathways. Network centrality analyses discover 28 high-value SARS-CoV-2 targets, which are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression. Our probabilistic modeling framework elucidates critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host modifying responses and cytokine storm. Overall, our network centric analyses reveal novel molecular components, uncover structural and functional modules, and provide molecular insights into SARS-CoV-2 pathogenicity that may foster effective therapeutic design. Funding This work was supported by the National Science Foundation (IOS-1557796) to M.S.M., and U54 ES 030246 from NIH/NIEHS to M. A. Conflict of Interest The authors declare no competing interests. The authors also declare no financial interests.