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

• Published in: Journal of medical microbiology Vol. 66; no. 9; pp. 1261 - 1274
• Main Authors: Rabaan, Ali A., Alahmed, Shamsah H., Bazzi, Ali M., Alhani, Hatem M.
• Format: Journal Article
• Language: English
• Published: England Microbiology Society 01.09.2017
• Subjects: Antiviral Agents - therapeutic use; Cathepsin L - antagonists & inhibitors; Coronavirus Infections - therapy; Coronavirus Infections - virology; Host-Pathogen Interactions; Humans; Interferons - therapeutic use; Middle East Respiratory Syndrome Coronavirus - drug effects; Middle East Respiratory Syndrome Coronavirus - genetics; Middle East Respiratory Syndrome Coronavirus - isolation & purification; Middle East Respiratory Syndrome Coronavirus - physiology; Prospective Studies; Review; Serine Endopeptidases - metabolism; Serine Proteinase Inhibitors - therapeutic use; Viral Vaccines - administration & dosage; Viral Vaccines - therapeutic use; Antiviral peptide; PL(pro); glycopeptide antibiotic; MERS-CoV; interferon; DPP4; protease; vaccine; lopinavir; camostat; M(pro); S protein; GLS-5300; convalescent plasma; monoclonal antibodies
• ISSN: 0022-2615; 1473-5644; 1473-5644
• DOI: 10.1099/jmm.0.000565

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.