Assessing the consequences of environmental exposures on the expression of the human receptor and proteases involved in SARS-CoV-2 cell-entry

Abstract

The role of environmental condition on the infection by the novel pathogenic SARS-CoV-2 virus remains uncertain. In here, exploiting a large panel of publicly available genome-wide data, we investigated whether the human receptor ACE2 and human proteases TMPRSS2 , FURIN and CATHEPSINs (B, L and V), which are involved in SARS-CoV-2 cell entry, are transcriptionally regulated by environmental cues. We report that more than 50 chemicals modulate the expression of ACE2 or human proteases important for SARS-CoV-2 cell entry. We further demonstrate that transcription factor AhR, which is commonly activated by pollutants, binds to the promoter of TMPRSS2 and enhancers and/or promoters of Cathepsin B, L and V encoding genes. Our exploratory study documents an influence of environmental exposures on the expression of genes involved in SARS-CoV-2 cell entry. These results could be conceptually and medically relevant to our understanding of the COVID-19 disease, and should be further explored in laboratory and epidemiologic studies.

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

“…In addition, Panx-1 blockers also reduce the secretion of proteases into the extracellular space, such as cathepsins (Swayne et al, 2020). Extracellular proteases, such as furin and cathepsins, promote SARS-CoV-2 infection over other coronaviruses, as demonstrated by others (Bestle et al, 2020;Dessie and Malik, 2021;Huffman et al, 2021;Murgolo et al, 2021;Raghav et al, 2021;Rossi et al, 2020;Watzky et al, 2021;Zhang et al, 2021), and our current data support these findings by identifying a novel mechanism of virus-mediated inflammation. Our data that ATP, PGE 2 , and IL1b are highly concentrated in the BAL obtained from COVID-19 individuals is exciting but needs to be considered carefully due to the fact that during the evolution of the disease, significant apoptosis of lung cells occurs (Liu et al, 2021).…”

Air pollution and COVID-19 mortality and hospitalization: An ecological study in Iran

“…Moreover, exposure to PM 2.5 in the long time can increase the protein expression of ACE-2 in A549 cells ( Du et al, 2020 ; Miyashita et al, 2020 ). The ACE-2 receptor could raise the viral RNA entering lungs cells and exacerbate the viral load of the COVID-19 virus ( Baildya et al, 2021 ; Watzky et al, 2021 ).…”

Reappraisal of Dietary Phytochemicals for Coronavirus Infection: Focus on Hesperidin and Quercetin

“…The internalisation of SARS-CoV-2 in human cells is mediated by the binding of the virus' spike glycoprotein (S) to its receptor on cell membranes, which is the angiotensin converting enzyme 2 (ACE2) [38,39]. ACE2 is expressed in many tissues including the lung, liver, heart, colon, oesophagus, intestine, kidney, and even the brain, which is consistent with the variety of cell types that can be infected, and the variety of symptoms reported in COVID-19 patients [40][41][42][43][44][45]. The S protein has two subunits, the first of which contains a receptor binding domain (RBD), which is responsible for binding to ACE2.…”