Coronaviruses and gastrointestinal diseases

Luo, Xiaodong; Zhou, Guan Zhou; Zhang, Yan; Li, Peng; Zou, Li; Yang, Yun

doi:10.1186/s40779-020-00279-z

Cited by 22 publications

(20 citation statements)

References 42 publications

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“…GI symptoms including diarrhea, abdominal pain, and vomiting have been reported in many cases ( Lin et al, 2020 ; Villapol, 2020 ) and are even considered as a common symptom for suspecting SARS-CoV-2 infection ( Lan et al, 2020 ; Villapol, 2020 ). Patients with NL63 also often exhibit GI symptoms, although they are not as severe ( Luo et al, 2020 ). However, it is not clear if this is due to direct infection of the intestine or due to systemic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Enteric Coronavirus Infection and Treatment Modeled With an Immunocompetent Human Intestine-On-A-Chip

Bein¹,

Kim²,

Goyal³

et al. 2021

Front. Pharmacol.

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Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human vascular endothelium to study host cellular and inflammatory responses to infection with NL63 coronavirus. These organoid-derived intestinal epithelial cells dramatically increased their ACE2 protein levels when cultured under flow in the presence of peristalsis-like mechanical deformations in the Intestine Chips compared to when cultured statically as organoids or in Transwell inserts. Infection of the intestinal epithelium with NL63 on-chip led to inflammation of the endothelium as demonstrated by loss of barrier function, increased cytokine production, and recruitment of circulating peripheral blood mononuclear cells (PBMCs). Treatment of NL63 infected chips with the approved protease inhibitor drug, nafamostat, inhibited viral entry and resulted in a reduction in both viral load and cytokine secretion, whereas remdesivir, one of the few drugs approved for COVID19 patients, was not found to be effective and it also was toxic to the endothelium. This model of intestinal infection was also used to test the effects of other drugs that have been proposed for potential repurposing against SARS-CoV-2. Taken together, these data suggest that the human Intestine Chip might be useful as a human preclinical model for studying coronavirus related pathology as well as for testing of potential anti-viral or anti-inflammatory therapeutics.

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Section: Discussionmentioning

confidence: 99%

Enteric Coronavirus Infection and Treatment Modeled With an Immunocompetent Human Intestine-On-A-Chip

Bein¹,

Kim²,

Goyal³

et al. 2021

Front. Pharmacol.

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show abstract

“…GI symptoms including diarrhea, abdominal pain, and vomiting have been reported in many cases 31,32 and are even considered as a common symptom for suspecting SARS-CoV-2 infection 31, 33 . Patients with NL63 also often exhibit GI symptoms, although they are not as severe 34 . Furthermore, infection of the GI tract by SARS-CoV-2 has been implicated in the severity of COVID-19 35 and it is involved in multi-system inflammatory disease 36 .…”

Section: Discussionmentioning

confidence: 99%

Enteric coronavirus infection and treatment modeled with an immunocompetent human intestine-on-a-chip

Bein¹,

Kim²,

Goyal³

et al. 2021

Preprint

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Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human vascular endothelium to study host cellular and inflammatory responses to infection with NL63 coronavirus. These organoid-derived intestinal epithelial cells dramatically increased their ACE2 protein levels when cultured under flow in the presence of peristalsis-like mechanical deformations in the Intestine Chips compared to when cultured statically as organoids or in Transwell inserts. Infection of the intestinal epithelium with NL63 on-chip led to inflammation of the endothelium as demonstrated by loss of barrier function, increased cytokine production, and recruitment of circulating peripheral blood mononuclear cells (PMBCs). Treatment of NL63 infected chips with the approved protease inhibitor drug, nafamostat, inhibited viral entry and resulted in a reduction in both viral load and cytokine secretion, whereas remdesivir, one of the few drugs approved for COVID19 patients, was not found to be effective and it also was toxic to the endothelium. This model of intestinal infection was also used to test the effects of other drugs that have been proposed for potential repurposing against SARS-CoV-2. Taken together, these data suggest that the human Intestine Chip might be useful as a human preclinical model for studying coronavirus related pathology as well as for testing of potential anti-viral or anti-inflammatory therapeutics.

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“…However, it was observed elsewhere that both bromhexine and ambroxol can cause a GIT disturbance, such as nausea, vomiting, and diarrhea [ 41 ]. Unfortunately, these unwanted side effects of bromhexine and ambroxol may worse the clinical symptoms among SARS-CoV-2 infected patients, who may be already suffer from GIT problems [ 42 ].…”

Section: Targeting Of Tmprss2 To Prevent Sars-cov-2 Entry To Gi Tract Enterocytes—potential Drugsmentioning

confidence: 99%

Targeting the intestinal TMPRSS2 protease to prevent SARS-CoV-2 entry into enterocytes-prospects and challenges

Mahmoud

Jarrar

2021

Mol Biol Rep

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The transmembrane protease serine 2 (TMPRSS2) is a membrane anchored protease that primarily expressed by epithelial cells of respiratory and gastrointestinal systems and has been linked to multiple pathological processes in humans including tumor growth, metastasis and viral infections. Recent studies have shown that TMPRSS2 expressed on cell surface of host cells could play a crucial role in activation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein which facilitates the rapid early entry of the virus into host cells. In addition, direct suppression of TMPRSS2 using small drug inhibitors has been demonstrated to be effective in decreasing SARS-CoV-2 infection in vitro, which presents TMPRSS2 protease as a potential therapeutic strategy for SARS-CoV-2 infection. Recently, SARS-CoV-2 has been shown to be capable of infecting gastrointestinal enterocytes and to provoke gastrointestinal disorders in patients with COVID-19 disease, which is considered as a new transmission route and target organ of SARS-CoV-2. In this review, we highlight the biochemical properties of TMPRSS2 protease and discuss the potential targeting of TMPRSS2 by inhibitors to prevent the SARS-CoV-2 spreading through gastro-intestinal tract system as well as the hurdles that need to be overcome.

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Coronaviruses and gastrointestinal diseases

Cited by 22 publications

References 42 publications

Enteric Coronavirus Infection and Treatment Modeled With an Immunocompetent Human Intestine-On-A-Chip

Enteric Coronavirus Infection and Treatment Modeled With an Immunocompetent Human Intestine-On-A-Chip

Enteric coronavirus infection and treatment modeled with an immunocompetent human intestine-on-a-chip

Targeting the intestinal TMPRSS2 protease to prevent SARS-CoV-2 entry into enterocytes-prospects and challenges

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