Published online Oct 21, 2021. doi: 10.3748/wjg.v27.i39.6590
Peer-review started: March 29, 2021
First decision: June 14, 2021
Revised: June 28, 2021
Accepted: September 19, 2021
Article in press: September 19, 2021
Published online: October 21, 2021
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seems to employ two routes of entrance to the host cell; via membrane fusion (with the cells expressing both angiotensin converting enzyme 2 (ACE2) and transmembrane peptidase/serine subfamily member 2/4 (TMPRSS2/4)) or via receptor-mediated endocytosis (to the target cells expressing only ACE2). The second mode is associated with cysteine cathepsins (probably cathepsin L) involvement in the virus spike protein (S protein) proteolytic activation. Also furin might activate the virus S protein enabling it to enter cells. Gastrointestinal tract (GIT) involvement in SARS-CoV-2 infection is evident in a subset of coronavirus disease 2019 (COVID-19) patients exhibiting GIT symptoms, such as diarrhea, and presenting viral-shedding in feces. Considering the abundance and co-localization of ACE2 and TMPRSS2 in the lower GIT (especially brush-border enterocytes), these two receptors seem to be mainly involved in SARS-CoV-2 invasion of the digestive tract. Additionally, in vitro studies have demonstrated the virions capability of infection and replication in the human epithelial cells lining GIT. However, also furin and cysteine cathepsins (cathepsin L) might participate in the activation of SARS-CoV-2 spike protein contributing to the virus invasiveness within GIT. Moreover, cathepsin L (due to its involvement in extracellular matrix components degradation and remodeling, the processes enhanced during SARS-CoV-2-induced inflammation) might be responsible for the dysregulation of absorption/ digestion functions of GIT, thus adding to the observed in some COVID-19 patients symptoms such as diarrhea.
Core Tip: Gastrointestinal tract (GIT) is believed to participate in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) dissemination. The current research shows the abundance and co-localization of angiotensin converting enzyme 2 (ACE2) and transmembrane peptidase/serine subfamily member 2 receptors in the lower GIT. Furthermore, about half of coronavirus disease 2019 patients present with GIT symptoms, such as diarrhea, and exhibit viral-shedding in feces. Additionally, in vitro studies have demonstrated the virions capability of infection and replication in the human epithelial cells lining GIT. This paper reviews the possible routes of the virus infection with respect to the host-enzymatic systems responsible for the proteolytic priming of SARS-CoV-2.