Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) has continuously posed a threat to public health worldwide, yet no therapeutics or vaccines are currently available to prevent or treat MERS-CoV infection. We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, m336 was found to have reduced efficacy against MERS-CoV strains with mutations in RBD, and HR2P-M2 showed low potency, thus limiting the clinical application of each when administered separately. However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. Thus, this combinatorial strategy could be used in clinics for the urgent treatment of MERS-CoV-infected patients.
Highlights
Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), a lineage C beta-coronavirus, was reported to cause severe respiratory tract infection [1,2]
We found that IC50 values of HR2P-M2 and m336 for inhibiting MERS-CoV pseudovirus infection were about 600 nM and 0.06 nM, respectively
MERS-CoV pseudovirus infection with combination index (CI) values of 0.13–0.20 for 50–90% inhibition, including potency enhancement of 12.9- to 18.9-fold for m336 and 8.4- to 12.9-fold for HR2P-M2. This result suggested that the MERS-CoV fusion inhibitory peptide HR2P-M2 and the MERS-CoV neutralizing mAb m336 could be used in combination to enhance anti-MERS-CoV activity
Summary
Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), a lineage C beta-coronavirus, was reported to cause severe respiratory tract infection [1,2]. 2266 laboratory-confirmed cases of infection with MERS-CoV, including 804 MERS-CoV associated deaths, have been reported to the. No effective therapeutics or vaccines are available to treat or prevent MERS-CoV infection. The spike (S) protein of MERS-CoV plays important roles in virus attachment, fusion, and entry into the target cell [3,4,5]. The S protein of MERS-CoV consists of S1 and. The S1 subunit is responsible for the binding of the virion by its receptor binding domain (RBD) to the cellular receptor, dipeptidyl peptidase-4 (DPP4), while the S2 subunit mediates the fusion
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