Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome: Current Therapeutic Options and Potential Targets for Novel Therapies

Abstract

No specific antivirals are currently available for two emerging infectious diseases, Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). A literature search was performed covering pathogenesis, clinical features and therapeutics, clinically developed drugs for repurposing and novel drug targets. This review presents current knowledge on the epidemiology, pathogenesis and clinical features of the SARS and MERS coronaviruses. The rationale for and outcomes with treatments used for SARS and MERS is discussed. The main focus of the review is on drug development and the potential that drugs approved for other indications provide for repurposing. The drugs we discuss belong to a wide range of different drug classes, such as cancer therapeutics, antipsychotics, and antimalarials. In addition to their activity against MERS and SARS coronaviruses, many of these approved drugs have broad-spectrum potential and have already been in clinical use for treating other viral infections. A wealth of knowledge is available for these drugs. However, the information in this review is not meant to guide clinical decisions, and any therapeutic described here should only be used in context of a clinical trial. Potential targets for novel antivirals and antibodies are discussed as well as lessons learned from treatment development for other RNA viruses. The article concludes with a discussion of the gaps in our knowledge and areas for future research on emerging coronaviruses.

Fig. 1

Maps of the severe acute respiratory syndrome (SARS) (a) and Middle East respiratory syndrome (MERS) (b) outbreaks with confirmed case numbers

Fig. 2

Genomes of Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) indicating the open reading frames for nonstructural (1a and 1b) and structural proteins (numbered 3–9, and E, M, N, S). E envelope, M membrane, N nucleocapsid, S Spike

Fig. 3

Candidate drugs for repurposing for coronaviral infections. Several drug classes (A through I) have been studied, and the steps/processes of the viral replication cycle that they most likely target are indicated. AKT serine/threonine kinase, CAD cationic amphiphilic drug, Cyps cytochrome P-450s, E envelope, ER endoplasmic reticulum, ERGIC ER–Golgi intermediate compartment, ERK extracellular signal-reduction kinase, IFN interferon, MAPK mitogen-activated protein kinase, M membrane, MPA mycophenolic acid, mTOR mechanistic target of rapamycin, N nucleocapsid, NFAT nuclear factor of activated T cells, ORF open reading frame, PI3K phosphoinositide 3-kinase, S Spike