Human cell receptors: potential drug targets to combat COVID-19

Raghav, Pawan Kumar; Kalyanaraman, Keerthana; Kumar, Dinesh

doi:10.1007/s00726-021-02991-z

Cited by 22 publications

(10 citation statements)

References 246 publications

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“…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).…”

Section: Analysis Of Bronchiolar Alveolar Lavage From Covid-19 Individuals Confirms the Accumulation Of Atp Pge 2 And Il1bsupporting

confidence: 85%

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

Luu¹,

Valdebenito²,

Scemes³

et al. 2021

iScience

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike protein and human coronavirus 229E (hCoV-229E) or its purified S protein, one of the main viruses responsible for the common cold, induce the transient opening of Pannexin-1 (Panx-1) channels in human lung epithelial cells. However, the Panx-1 channel opening induced by SARS-CoV-2 is greater and more prolonged than hCoV-229E/S protein, resulting in an enhanced ATP, PGE 2 , and IL-1b release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE 2 , and IL-1b levels. Panx-1 channel opening induced by SARS-CoV-2 spike protein is angiotensin-converting enzyme 2 (ACE-2), endocytosis, and furin dependent. Overall, we demonstrated that Panx-1 channel is a critical contributor to SARS-CoV-2 infection and should be considered as an alternative therapy.

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Section: Analysis Of Bronchiolar Alveolar Lavage From Covid-19 Individuals Confirms the Accumulation Of Atp Pge 2 And Il1bsupporting

confidence: 85%

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

Luu¹,

Valdebenito²,

Scemes³

et al. 2021

iScience

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“…Epithelial cells of the oral cavity, nasal duct, and upper airway are the primary targets for SARS-CoV-2 [ 1 , 2 , 3 ], by the interaction of the viral spike protein (S-protein) with the human angiotensin converting enzyme 2 (ACE2) and other host proteins and glycosaminoglycans [ 4 , 5 ]. Moreover, a recent study defined the susceptibility to SARS-CoV-2 infection as the result of a combination between the genetic variations of SARS-CoV-2 and the genetics of the host [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

OM-85 Broncho-Vaxom®, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells

et al. 2021

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In clinical studies, OM-85 Broncho-Vaxom®, a bacterial lysate, reduced viral respiratory tract infection. Infection of epithelial cells by SARS-CoV-2 depends on the interaction of its spike-protein (S-protein) with host cell membrane proteins. In this study, we investigated the effect of OM-85 on the expression of S-protein binding proteins by human bronchial epithelial cells. Human bronchial epithelial cells were treated with OM-85 over 5 days. The expression of SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2), transmembrane protease serine subtype 2 (TMPRSS2), dipeptidyl peptidase-4 (DPP4), and a disintegrin and metalloprotease 17 (ADAM17) were determined by Western blotting and quantitative RT-PCR. Soluble (s)ACE2, heparan sulfate, heparanase, and hyaluronic acid were assessed by ELISA. OM-85 significantly reduced the expression of ACE2 (p < 0.001), TMPRSS2 (p < 0.001), DPP4 (p < 0.005), and cellular heparan sulfate (p < 0.01), while ADAM17 (p < 0.02) expression was significantly upregulated. Furthermore, OM-85 increased the level of sACE2 (p < 0.05), hyaluronic acid (p < 0.002), and hyaluronan synthase 1 (p < 0.01). Consequently, the infection by a SARS-CoV-2 spike protein pseudo-typed lentivirus was reduced in cells pretreated with OM-85. All effects of OM-85 were concentration- and time-dependent. The results suggest that OM-85 might reduce the binding of SARS-CoV-2 S-protein to epithelial cells by modification of host cell membrane proteins and specific glycosaminoglycans. Thus, OM-85 might be considered as an add-on for COVID-19 therapy.

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“…L-SIGN is already widely studied in diseases that affect the liver, such as diseases caused by the hepatitis C virus, the human immunodeficiency virus, the Rift Valley fever virus, the Uukuniemi virus, and the Toscana virus[ 9 ]. A recent study supports this hypothesis by suggesting that L-SIGN may provide a new way for SARS-CoV-2 to enter human cells[ 10 ]. In COVID-19, autopsy studies showed that SARS-CoV-2-infected hepatic sinusoid cells expressed more L-SIGN receptors compared to control groups[ 11 ].…”

Section: To the Editormentioning

confidence: 88%

COVID-19, liver dysfunction and pathophysiology: A conceptual discussion

Júnior¹

2022

WJG

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The intra and extracellular pathways of hepatic injury by coronavirus disease 2019 (COVID-19) are still being studied. Understanding them is important to treat this viral disease and other liver and biliary tract disorders. Thus, this paper aims to present three hypotheses about liver injury caused by COVID-19: (1) The interactions between severe acute respiratory syndrome coronavirus 2 spike protein and membrane receptors in the hepatocyte; (2) The dysbiosis and “gut-liver axis” disruption in patients with serious clinical presentations of COVID-19; and (3) The inflammatory response exacerbated through the production of interleukins such as interleukin-6. However, despite these new perspectives, the pathophysiological process of liver injury caused by COVID-19 is still complex and multifactorial. Thus, understanding all these variables is a challenge to science but also the key to propose individualized and effective patient therapies.

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Human cell receptors: potential drug targets to combat COVID-19

Cited by 22 publications

References 246 publications

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

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

OM-85 Broncho-Vaxom®, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells

COVID-19, liver dysfunction and pathophysiology: A conceptual discussion

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