In 2012, a new SARS-like coronavirus emerged in the Middle East, namely the Middle East respiratory syndrome coronavirus (MERS-CoV). It has caused outbreaks with high mortality. During infection of target cell, MERS-CoV S protein S1 subunit binds to the cellular receptor (DPP4), and its S2 subunit HR1 and HR2 regions intact with each other to form a stable six-helix bundle to mediate the fusion between virus and target cell membranes. Hence, blocking the process of six-helix bundle formation can effectively inhibit MERS-CoV entry into the target cells. This review focuses on the recent advance in the development of peptidic entry inhibitors targeting the MERS-CoV S2 subunit.
Antiviral Agents ; pharmacology ; Coronavirus Infections ; drug therapy ; Dipeptidyl Peptidase 4 ; metabolism ; Drug Design ; Humans ; Middle East Respiratory Syndrome Coronavirus ; drug effects ; physiology ; Peptides ; pharmacology ; Spike Glycoprotein, Coronavirus ; metabolism ; Virus Internalization ; drug effects

Middle East respiratory syndrome coronavirus (MERS-CoV) causes high fever, cough, acute respiratory tract infection and multiorgan dysfunction that may eventually lead to the death of the infected individuals. MERS-CoV is thought to be transmitted to humans through dromedary camels. The occurrence of the virus was first reported in the Middle East and it subsequently spread to several parts of the world. Since 2012, about 1368 infections, including ~487 deaths, have been reported worldwide. Notably, the recent human-to-human \'superspreading' of MERS-CoV in hospitals in South Korea has raised a major global health concern. The fatality rate in MERS-CoV infection is four times higher compared with that of the closely related severe acute respiratory syndrome coronavirus infection. Currently, no drug has been clinically approved to control MERS-CoV infection. In this study, we highlight the potential drug targets that can be used to develop anti-MERS-CoV therapeutics.
Animals ; Antiviral Agents/*pharmacology ; Cell Line ; Coronavirus Infections/drug therapy/*epidemiology/metabolism/*transmission ; Dipeptidyl Peptidase 4/metabolism ; Disease Outbreaks ; Drug Discovery ; Host-Pathogen Interactions/drug effects ; Humans ; Middle East Respiratory Syndrome Coronavirus/drug effects/*physiology ; Molecular Targeted Therapy ; Spike Glycoprotein, Coronavirus/metabolism