MERS-CoV spike protein: a key target for antivirals

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.

An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies

“…The RBDs of SARS-CoV and MERS-CoV contain multiple conformation-dependent neutralizing epitopes that induce more potent neutralizing antibodies and protective efficacy against SARS-CoV and MERS-CoV infections, respectively, than other regions in S protein [5,8,9]. Modification of MERS-CoV S-RBD amino acid residues based on the structure design could improve its protection against MERS-CoV infection [9], suggesting that 2019-nCoV S-RBD or modified S-RBD of other coronavirus may be applied for developing 2019-nCoV vaccines.…”

A secretary bi-cistronic baculovirus expression system with improved production of the HA1 protein of H6 influenza virus in insect cells and Spodoptera litura larvae

“…The baculovirus expression system presented in this study may serve as an effective vector to construct virus-like particles for vaccine production. Although this system expressed H6HA1-His protein and secreted into the medium efficiently, we found that it was not successful in producing the spike protein (S1) of Middle East respiratory syndrome coronavirus (Du et al, 2017). The secretion of S1 was poor, even though it was expressed at adequate level in the cell (data not shown).…”

Preparation of virus-like particle mimetic nanovesicles displaying the S protein of Middle East respiratory syndrome coronavirus using insect cells

“…The S1 subunit contains the receptor binding domain, and the S2 subunit is required for the membrane fusion of MERS-CoV. Therefore, the S protein is one of the targets for the development of MERS-CoV therapeutics (Du et al, 2017). Some neutralizing antibodies have been developed against the receptor-binding domain of S protein, which blocks the interaction of S protein with it is coexpressed with the E or N protein in insect cells and mammalian cells (Mortola and Roy, 2004;Siu et al, 2008).…”