Investigating the human protein-host protein interactome of SARS-CoV-2 infection in the small intestine

Deciphering the tissue and organ interactions of the SARS-CoV-2 can be important to discern the potential underlying mechanisms and characterize drug candidates. Gastrointestinal symptoms and inflammation were frequently reported in the coronavirus disease 2019 (COVID-19). The expression pattern of ACE2 in the small intestinal as a major host receptor for SARS-CoV-2 and digestion-related enzyme has been determined. Here, we investigated interactome of the SARS-CoV-2–host protein in the small intestine tissue to detect highly clustered modules and associated mechanisms. 13 primary protein neighbors were found for ACE2 among the small intestine-specific proteins. The first module with the highest score was found as key module, since ACE2 and its four partners were observed in this module. Moreover, 8 host proteins were belonged to the highly clustered module. Functional analysis of this module highlighted protein digestion and absorption as a significant KEGG pathway with enriched genes of ACE2, MEP1A, MEP1B, DPP4, and XPNPEP2. Regulatory network revealed possible upstream regulating transcription factors that HNF factors including HNF4A, HNF1A, and HNF1B were found to be regulating the expression of ACE2 target gene. Drug-target interactions revealed associated drug classes. The SARS-CoV-2–host protein interactome revealed the important elements for virus infection in the small intestine that may help to clarify gastrointestinal symptoms and inflammation.