A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective.

Ali A Rabaan,Shamsah H Alahmed,Hatem M Alhani,Ali M Bazzi

doi:10.1099/jmm.0.000565

Abstract

There have been 2040 laboratory-confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) in 27 countries, with a mortality rate of 34.9 %. There is no specific therapy. The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir–ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The development of specific therapies and vaccines is therefore urgently required. We examine existing and potential therapies and vaccines from a molecular perspective. These include viral S protein targeting; inhibitors of host proteases, including TMPRSS2, cathepsin L and furin protease, and of viral M(pro) and the PL(pro) proteases; convalescent plasma; and vaccine candidates. The Medline database was searched using combinations and variations of terms, including ‘Middle East respiratory syndrome coronavirus’, ‘MERS-CoV’, ‘SARS’, ‘therapy’, ‘molecular’, ‘vaccine’, ‘prophylactic’, ‘S protein’, ‘DPP4’, ‘heptad repeat’, ‘protease’, ‘inhibitor’, ‘anti-viral’, ‘broad-spectrum’, ‘interferon’, ‘convalescent plasma’, ‘lopinavir ritonavir’, ‘antibodies’, ‘antiviral peptides’ and ‘live attenuated viruses’. There are many options for the development of MERS-CoV-specific therapies. Currently, MERS-CoV is not considered to have pandemic potential. However, the high mortality rate and potential for mutations that could increase transmissibility give urgency to the search for direct, effective therapies. Well-designed and controlled clinical trials are needed, both for existing therapies and for prospective direct therapies.

Highlights

Middle East respiratory syndrome coronavirus overviewMiddle East respiratory syndrome coronavirus (MERSCoV) was first isolated in Jeddah in the Kingdom of Saudi Arabia (KSA) from a 60-year-old male hospital patient, who died 24 June 2012, 11 days after presenting with acute pneumonia and subsequent renal failure [1]
Most cases have occurred in the Middle East, in KSA
The outbreak in Korea resulted in MERS-CoV emergence in second- and third-generation contacts, highlighting the potential for mutational changes that could increase the likelihood of human–human transmission [14, 18]

Summary

Introduction

Middle East respiratory syndrome coronavirus overviewMiddle East respiratory syndrome coronavirus (MERSCoV) was first isolated in Jeddah in the Kingdom of Saudi Arabia (KSA) from a 60-year-old male hospital patient, who died 24 June 2012, 11 days after presenting with acute pneumonia and subsequent renal failure [1]. Vaccination of mice by subcutaneous or intraperitoneal injection with MVA expressing full-length S protein induces robust and sustained MERS-CoV-specific neutralizing antibody and cytotoxic T lymphocyte responses, including in mice expressing human DPP4 [98].

Results

Conclusion