Systemic Analysis of Tissue Cells Potentially Vulnerable to Sars-Cov-2 Infection by the Protein-Proofed Single-Cell Rna Profiling of Ace2, Tmprss2 and Furin Proteases

SARS-CoV-2 receptor networks in diabetic and COVID-19–associated kidney disease

“…A more extensive set of interferon receptors, interferon-stimulated genes, and cytokines were differentially expressed in the COV ACE2þ signature ( Supplementary Table S10) compared with the DKD ACE2þ signature. In addition, the COV ACE2þ signature also had significant concordance with other reported SARS-CoV-2 datasets 20,36,39,40 (Table 3), sharing key viral processes such as viral regulation, interferon response, stress signaling, and endomembrane organization and transport (as evidenced by significant enrichments of the SARS-CoV-2 infection gene list 36 in COV ACE2þ signature modules M3, M5, M6, and others, as depicted in Figure 7c and listed in Supplementary Table S14). This is further confirmed by examination of the processes that are enriched when the PTEC network is clustered with only the shared genes (intersection of COV ACE2þ signature and the SARS-CoV-2 infection set from Bojkova et al 36 ( Supplementary Table S15).…”

“…We compared the DKD ACE2þ signature genes with published SARS-CoV-2-relevant gene sets 20,36,39,40 (see Methods). In each comparison, a significant fraction of each of the SARS-CoV-2 gene sets was shared with the DKD ACE2þ signature (Table 3), suggesting a set of common responses to SARS-CoV-2 infection shared with the DKD ACE2þ signature.…”

“…16 As with the coronavirus (SARS-CoV) 17,18 that caused severe acute respiratory syndrome in the early 2000s, angiotensinconverting enzyme 2 (ACE2) is the primary cell-entry receptor for SARS-CoV-2. 16,19,20 ACE2 expression levels correlate with higher risk of SARS-CoV-2 infection. 9,21,22 ACE2, a membrane-bound metallopeptidase, is a master regulator of the renin-angiotensin-aldosterone system (RAAS).…”

“…107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 SARS-CoV-2 can also be internalized and the S protein can be cleaved in the endosomal compartment by acid-activated proteases such as cathepsin-L and dipeptidyl peptidase 4, both of which are involved in glucose metabolism and immune systems. 8,20,[28][29][30] Single-cell RNA sequencing (scRNAseq) of SARS-CoV-2 target tissues provides a way to identify specific cell types with enhanced ACE2 expression and determine whether these cells possess molecular machinery that facilitate viral entry and subsequent virus-induced cytotoxicity. Characterization of these molecular processes could greatly accelerate the identification and development of novel therapeutic options for SARS-CoV-2 infection and noninvasive means for stratifying individuals at risk for COVID-19.…”

Incidence, patterns, risk factors, and histopathological findings of liver injury in coronavirus disease 2019 (COVID-19): a scoping review

“…65 Significant necrosis of and rapid viral replication within cholangiocytes has also been observed by Zhao et al 65 in a human liver ductal organoid model. However, Zhou et al 66 argued against this proposed mechanism by highlighting that ACE2Rs on cholangiocytes are confined to the apical surface, from where viral invasion is unlikely. Furthermore, the hepatic pattern of LFT elevation fails to explain this possible ductal pathology.…”