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

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.

The differences in SARS-CoV and SARS-CoV-2 specific co-expression network mediated biological process in human gut enterocytes.

Novel coronavirus SARS-CoV-2 was recently outbreak worldwide causes severe acute respiratory syndrome along with gastrointestinal symptoms for some infected patients. Information on detail pathogenesis, host immune responses and responsible biological pathways are limited. Therefore, infection specific host gut responses and dietary supplements to neutralize immune inflammation demand extensive research. This study aimed to find differences in global co-expression protein-protein interaction sub-network and enriched biological processes in SARS-CoV and SARS-CoV-2 infected gut enterocytes cell line. Attempts have also been made to predict some dietary supplements to boost human health. The SARS-CoV and SARS-CoV-2 infected differential express proteins were integrated with the human protein interaction network and co-expression subnetworks were constructed. Common hubs of these sub-networks reshape central cellular pathways of metabolic processes, lipid localization, hypoxia response to decrease oxygen level and transport of bio-molecules. The major biological process enriched in the unique hub of SARS-CoV-2 significantly differ from SARS-CoV, related to interferon signaling, regulation of viral process and influenza-A enzymatic pathway. Predicted dietary supplements can improve SARS-CoV-2 infected person''s health by boosting the host immunity/reducing inflammation. To the best of our knowledge this is the first report on co-expression network mediated biological process in human gut enterocytes to predict dietary supplements/compounds.

Characterization of Porcine Epidemic Diarrhea Virus Isolate US/Iowa/18984/2013 Infection in 1-Day-Old Cesarean-Derived Colostrum-Deprived Piglets.

Porcine epidemic diarrhea virus (PEDV) was first recognized in North America in April 2013 and has since caused devastating disease. The objective of this study was to characterize disease and viral detection associated with an original North American PEDV isolate inoculated in neonatal piglets. Thirty-six 1-day-old cesarean-derived and colostrum-deprived piglets were randomly assigned to the control (n = 16) or challenged group (n = 20); the latter were orogastrically inoculated with 1 ml of US/Iowa/18984/2013 PEDV isolate titered at 1 × 10(3) plaque-forming units per milliliter. Rectal swabs were collected from all piglets prior to inoculation and every 12 hours postinoculation (hpi) thereafter, with 4 control and 5 challenged piglets euthanized at 12, 24, 48, and 72 hpi. One piglet had a positive real-time quantitative polymerase chain reaction test on rectal swab at 12 hpi, and all remaining piglets were positive thereafter, with highest viral quantities detected at 24 and 36 hpi. Diarrhea was evident in 30% and 100% of challenged piglets at 18 and 24 hpi, respectively. Viral antigen was detected in enterocytes by immunohistochemistry in the duodenum and ileum of piglets euthanized at 12 hpi and was apparent throughout the small intestine of all piglets thereafter, with villus height:crypt depth ratios consistently below 4:1. Viremia was confirmed in 18 of 20 pigs at euthanasia. Clinical disease was severe and developed rapidly following infection with an original North American PEDV isolate, with lesions, viremia, and antigen detection possible by 12 hpi.