Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC

Abstract

Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals. However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread. Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection. Viral genome analysis revealed close relatedness to coronaviruses found in bats. Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (Pipistrellus pipistrellus) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoV-EMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.

Viral infection in community-acquired pneumonia: a systematic review and meta-analysis

“…An example is a recent case series demonstrating good outcomes with early administration of cidofovir for non-immunocompromised patients with severe CAP [38]. Additionally, there are a number of new antivirals being developed [39][40][41]. The prospect of new therapeutic options for viral infection in CAP highlights the increasing role that diagnostic tests for viral infection are likely to have in the near future.…”

What are our pharmacotherapeutic options for MERS-CoV?

“…Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a functional receptor for the newly discovered MERS-CoV [8]. The expression of DPP4 was found in primary human bronchiolar epithelial cell cultures and human bronchial lung tissue.…”

“…An in vitro study of MERS-CoV infection in ferrets showed that adenosine deaminase, a DPP4 binding protein, competed for virus binding and exhibited a natural antagonist for MERS-CoV infection [9]. For the search of an effective therapy, the domains of DPP4 (CD26) were required for the binding of MERS-CoV [8,10]. Anti-CD26 polycolnal antibody showed in vitro inhibitory effect of MERS-CoV infection [8].…”

“…For the search of an effective therapy, the domains of DPP4 (CD26) were required for the binding of MERS-CoV [8,10]. Anti-CD26 polycolnal antibody showed in vitro inhibitory effect of MERS-CoV infection [8]. A humanized anti-CD26 monoclonal antibody (mAb YS110), which recognizes six distinct epitopes of the CD26 molecule, had an inhibitory effect of infection with MERS-CoV [10].…”

“…sitagliptin, vildagliptin or saxagliptin [8]. The development of inhibitors that target the binding site and receptors (DPP4) may prove to be of benefit for the therapy of MERS-CoV infection [9].…”