Abstract
Since emerging in 2012, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has been a global public health threat with a high fatality rate and worldwide distribution. There are no approved vaccines or therapies for MERS until now. Passive immunotherapy with neutralizing monoclonal antibodies (mAbs) is an effective prophylactic and therapeutic reagent against emerging viruses. In this article, we review current advances in neutralizing mAbs against MERS-CoV. The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. A major problem with neutralizing mAb therapy is mutant escape under selective pressure, which can be solved by combination of neutralizing mAbs targeting different epitopes. Neutralizing mAbs are currently under preclinical evaluation, and they are promising candidate therapeutic agents against MERS-CoV infection.
Highlights
Middle East Respiratory Syndrome (MERS) emerged in 2012 in Saudi Arabia with the death of a man with pneumonia; the causative agent was subsequently identified as MERS-CoV, which belonged to lineage C betacoronaviruses [1]
We review the current knowledge on neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of MERS-CoV
The 4C2 complex interfered with MERS-CoV binding to DPP4 by both steric hindrance and interface-residue competition. 2E6 competed with 4C2 to bind to MERS-RBD, indicating that they recognized proximate or overlapping epitopes [10]
Summary
Middle East Respiratory Syndrome (MERS) emerged in 2012 in Saudi Arabia with the death of a man with pneumonia; the causative agent was subsequently identified as MERS-CoV, which belonged to lineage C betacoronaviruses [1]. Given the potential risk of causing worldwide public health emergencies and the absence of licensed vaccines and antiviral therapeutics, the World Health Organization has listed MERS-CoV in the “List of Blueprint priority diseases” (http://www.who.int/blueprint/priority-diseases/en/). Vaccines are the most important approach against viral infections, but usually take a long time to develop They are unable to provide either immediate prophylactic protection or treat ongoing viral infections. The S protein (1353 aa) plays an important role in virus infection and consists of a receptor-binding subunit S1 (aa 18–751) and a membrane-fusion subunit S2 Neutralizing mAbs binding to the S protein of MERS-CoV can prevent viral attachment to the cell receptor and inhibit viral entry [7]. We review the current knowledge on neutralizing mAbs targeting the RBD of MERS-CoV
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