MERS-CoV spike protein: a key target for antivirals
EXPERT OPINION ON THERAPEUTIC TARGETS
Authors: Du, Lanying; Yang, Yang; Zhou, Yusen; Lu, Lu; Li, Fang; Jiang, Shibo
Abstract
Introduction: The continual Middle East respiratory syndrome (MERS) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat MERS coronavirus (MERS-CoV) infection. A surface spike (S) protein guides MERS-CoV entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (DPP4), followed by fusion between virus and host cell membranes. MERS-CoV S protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion.Areas covered: This review illustrates MERS-CoV S protein's structure and function, particularly S1 receptor-binding domain (RBD) and S2 heptad repeat 1 (HR1) as therapeutic targets, and summarizes current advancement on developing anti-MERS-CoV therapeutics, focusing on neutralizing monoclonal antibodies (mAbs) and antiviral peptides.Expert opinion: No anti-MERS-CoV therapeutic is approved for human use. Several S-targeting neutralizing mAbs and peptides have demonstrated efficacy against MERS-CoV infection, providing feasibility for development. Generally, human neutralizing mAbs targeting RBD are more potent than those targeting other regions of S protein. However, emergence of escape mutant viruses and mAb's limitations make it necessary for combining neutralizing mAbs recognizing different neutralizing epitopes and engineering them with improved efficacy and reduced cost. Optimization of the peptide sequences is expected to produce next-generation anti-MERS-CoV peptides with improved potency.
Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease Patients
EMERGING INFECTIOUS DISEASES
Authors: Okba, Nisreen M. A.; Mueller, Marcel A.; Li, Wentao; Wang, Chunyan; GeurtsvanKessel, Corine H.; Corman, Victor M.; Lamers, Mart M.; Sikkema, Reina S.; de Bruin, Erwin; Chandler, Felicity D.; Yazdanpanah, Yazdan; Le Hingrat, Quentin; Descamps, Diane; Houhou-Fidouh, Nadhira; Reusken, Chantal B. E. M.; Bosch, Berend-Jan; Drosten, Christian; Koopmans, Marion P. G.; Haagmans, Bart L.
Abstract
A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein-specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2-infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.