Ralph A Tripp*
University of Georgia, Department of Infectious Diseases, Athens, GA USA
Received Date: August 22, 2013; Accepted Date: August 23, 2013; Published Date: August 27, 2013
Citation: Tripp RA (2013) Therapeutic Considerations for Middle East Respiratory Syndrome Coronavirus. J Antivir Antiretrovir 5:xxi-xxii. doi: 10.4172/jaa.1000e109
Copyright: © 2013 Tripp RA. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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MERS; Coronavirus; MERS-CoV; Antiviral; Therapeutic; DPP4; CD26
The emergence of novel infectious diseases continually poses a threat to animal and human health. This has been exemplified by the emergence of several viruses including pandemic H1N1 influenza virus, H7N9 influenza virus, H5N1 highly pathogenic avian influenza virus, and SARS-coronavirus (SARS-CoV). Recently, a novel respiratory virus has emerged from the Middle East, specifically Middle East Respiratory Syndrome (MERS) coronavirus (MERS-CoV) in June 2012 in Saudi Arabia . MERS-CoV was first isolated from a 60 year old Saudi male who died of severe pneumonia . Subsequently, other confirmed cases have been reported [3,4]. Coronaviruses are a family of viruses that cause a spectrum of illnesses in humans ranging from the common cold to severe acute respiratory syndrome . Coronaviruses are also cause disease in a wide variety of animal species . Perhaps the biggest unknown concerning the emergence of this disease is why MERS-CoV out breaks has been limited to the Middle East, and what the method of zoonotic transmission to humans.
MERS-CoV virus is thought to be an animal virus that resulted in human infections; however, there is currently no direct evidence for an animal origin. The fact that human cases have been sporadic with epidemiology suggesting that there has been long periods of time between cases and that the cases have occurred over wide-spread geographical areas has confounded identification of potential animal sources. It is important to note that MERS-CoV cases have occurred in clusters and in general without sustained human-to-human transmission [6,7], but human-to-human transmission has occurred in hospital settings, among family members, and at the work place [3,7,8]. Many questions remain unanswered as to the virus reservoir, and unlike SARS-CoV, bats do not seem to be the reservoir, and it remains unclear how people are becoming infected [4,9]. However, anecdotal exposure histories suggested that perhaps had been in contact with dromedary camels or goats, thus painting these animals as potential targets. Recent serological studies indicate that MERS-CoV or a related virus has infected camel populations, and rates of seroprevalence in sera from different locations suggest widespread infection [10,11].
Although the majority of coronavirus infections in humans are mild, the 2002 SARS-CoV outbreak and the emergence of MERSCoV highlight the need to rapidly develop new disease intervention strategies [12,13]. Much had been learned from studies investigating the molecular biology of how coronaviruses co-opt the host for replication. Understanding the universal mechanisms used by all coronaviruses to replicate can be used in the development of therapeutics for coronavirus infections. One example is the finding that coronavirus replication and transcription are governed by a complex that is anchored in internal host cell membranes [14-16]. These membranes provide a framework for viral genome replication by localizing and concentrating host factors needed for replication. Thus, therapeutics that disrupts membrane anchoring may provide a path forward for governing virus replication and disease pathogenesis.
The novel human coronavirus discovered in 2012, initially termed human coronavirus-Erasmus Medical Center (hCoV-EMC) , but renamed MERS-CoV, was shown to replicate in several mammalian cell lines that express dipeptidyl peptidase 4 (DPP4) - also known as CD26 [18,19]. It was shown that DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells . Importantly, antibodies specific to DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells, suggesting a strategy for therapeutic intervention and vaccination. DPP4 is a widely distributed protein that comes in secreted and membrane-bound forms, and is an evolutionary conserved serine-protease . As serine-protease inhibitors to DPP4 are available , and serine-protease inhibitors are effective for several viruses [22-27], this is another path forward for potential antiviral treatments against MERS-CoV that need to be explored. In addition, such studies will contribute to our understanding of the pathogenesis of this emerging human coronavirus, and hopefully facilitate the development of intervention strategies.