Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein

The recent outbreak of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) infection has led to more than 800 laboratory-confirmed MERS cases with a high case fatality rate (∼35%), posing a serious threat to global public health and calling for the development of effective and safe therapeutic and prophylactic strategies to treat and prevent MERS-CoV infection. Here we discuss the most recent studies on the structure of the MERS-CoV spike protein and its role in virus binding and entry, and the development of MERS-CoV entry/fusion inhibitors targeting the S1 subunit, particularly the receptor-binding domain (RBD), and the S2 subunit, especially the HR1 region, of the MERS-CoV spike protein. We then look ahead to future applications of these viral entry/fusion inhibitors, either alone or in combination with specific and nonspecific MERS-CoV replication inhibitors, for the treatment and prevention of MERS-CoV infection.