TWIRLS, an automated topic-wise inference method based on massive literature, suggests a possible mechanism via ACE2 for the pathological changes in the human host after coronavirus infection

Xiaoyang Ji; Chunming Zhang; Yubo Zhai; Zhonghai Zhang; Yiqing Xue; Chunli Zhang; Guangming Tan; Gang Niu

Combining with generalized interaction databases provides richer interactions and regulatory linkages. We extended the 119 CSHGs to their 2 o networks based on the interactions with higher likelihood of connections (Combined score> 800). The 2 o networks expanded the number of genes from 119 host genes to 3,494 genes that may be associated with coronavirus (see Table S1 , Sheet 6 with DPP4 [12] . The different distribution of these receptors in the respiratory tract results in different degrees of infection. Although the infection ability of MERS is lower than in SARS, the mortality is higher (in about one-third of patients) because of the deeper infection site [13] . Similar to the SARS virus, viral genomics and structural biology studies have shown that ACE2 is also a functional receptor for the new SARS-CoV-2 coronavirus. After binding to ACE2 via its Spike protein, SARS-CoV-2 undergoes membrane fusion and enters the host cells by endocytosis. The ACE2 peptidase is a key regulator of the Renin-Angiotensin System (RAS). It is highly expressed in the heart, kidney, and testis, and is also expressed at lower levels in other tissues (mainly in the intestine and lungs) [14, 15] . Recent studies have shown that the binding of the S protein to ACE2 in the new coronavirus is 10 to 20 times stronger than in the SARS virus [16] , which may help the new coronavirus infect the host through the upper respiratory tract, significantly increasing its infectivity. Using TWIRLS, we were able to identify both ACE2 and DPP4 genes as CSHGs, and both were significantly associated with the C5 category. The HR label for this category is "associated with S protein."