Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus

Timothy M. Uyeki; Karl J. Erlandson; George Korch; Michael O'Hara; Michael Wathen; Jean Hu-Primmer; Sally Hojvat; Erik J. Stemmy; Armen Donabedian

Disclosures

Emerging Infectious Diseases. 2016;22(7):e1-e11. 

In This Article

Therapeutic Drugs

No investigational therapeutic drugs have been evaluated for treatment of MERS-CoV patients in prospective randomized controlled clinical trials. Potential therapeutic drugs for MERS-CoV patients include available approved drugs with nonspecific properties, such as immunomodulators, small-molecule drugs with broad antiviral activity, repurposed FDA-approved small-molecule drugs that show activity against MERS-CoV in vitro (Table 3),[34,35] and newly developed monoclonal or polyclonal antibody therapies with specific activity against MERS-CoV (Table 4).[54]

One promising approach has been to investigate libraries of drugs approved by the FDA and the European Medicines Agency. Considering development times and manufacturing requirements for new products, repurposing of existing drugs might potentially facilitate a rapid response to outbreaks of emerging viruses (see Regulatory section for a discussion on repurposing). Other early-stage work on MERS-CoV therapeutics includes studies focusing on the essential viral replication steps of fusion, proteolysis, and RNA polymerization (Table 3).[54]

Immunotherapeutics under evaluation consist of convalescent plasma and monoclonal and polyclonal antibodies. Most of the monoclonal antibodies in development have specific neutralizing activity against the MERS-CoV spike protein.[55,56] Platforms are being developed to rapidly discover monoclonal antibodies, either from fully human convalescent blood or from transgenic animals, which can be manufactured on a large scale and are likely to have a good safety profile. The most advanced immunotherapeutic for MERS-CoV uses a transchromosomal bovine production system to produce fully human polyclonal MERS-CoV antibodies; a phase I study of this product was recently implemented (;[57] https://clinicaltrials.gov/ct2/show/NCT02788188). Preliminary results from immunoprophylaxis or treatment studies have shown efficacy of fully human monoclonal or polyclonal antibodies in MERS-CoV-infected mice and NHPs (Table 4). Although fully human monoclonal antibodies typically have a good safety profile and a defined set of preclinical toxicology studies, challenges to development of immunotherapeutics include ensuring the absence of antibody-dependent enhancement of disease and reducing the risk for generation of escape mutant viruses that would be resistant to treatment.

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