SUMMARY Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus that is associated with a high mortality rate (~36%) and is endemic in the Middle East. Since 2012, there have been 2100 laboratory confirmed cases and 730 deaths associated with MERS-CoV in 27 countries. Clinical manifestations of the virus range from asymptomatic to acute respiratory distress syndrome (ARDS), septic shock, and renal failure resulting in death. Bats are the natural reservoirs of MERS-CoV and can travel over long distances to transmit the virus to different intermediate hosts and humans. This, combined with the MERS-CoV spike (S) protein’s ability to undergo mutations that increase its transmission efficiency, gives the virus a pandemic potential. Currently there is a lack of knowledge on how viral and host factors contribute to the transmission and pathogenesis of MERS-CoV in humans. This article explores the different viral and host factors associated with MERS-CoV transmission and pathogenesis, and how this knowledge can aid in the development of therapeutics. MERS-CoV transmission is facilitated by interaction between the viral receptor binding domain of the S protein and the host receptor dipeptidyl peptidase 4 (DPP4). MERS-CoV can utilize multiple host proteases such as furin, transmembrane serine proteinase 2 (TMPRSS2), trypsin, and cathepsin to cleave the S protein, which facilitates membrane fusion. MERS-CoV has been shown to primarily infect cells in the lower respiratory tract of humans, but it can also infect immune and kidney cells. An overactive inflammatory response, induction of apoptosis, and cytokine dysregulation are vital factors that contribute to the high pathogenicity associated with MERS-CoV infection. Future treatment options for MERS-CoV include inhibition of virus entry, fusion, polyprotein cleavage, and replication by targeting both viral and host factors.
MERS-CoV: Identifying Viral and Host Factors Associated with Transmission, Pathogenesis, and Treatment Development
Fall 2017 / Winter 2018