A Fusion Peptide in the Spike Protein of MERS Coronavirus

Abstract

Coronaviruses represent current and emerging threats for many species, including humans. Middle East respiratory syndrome-related coronavirus (MERS-CoV) is responsible for sporadic infections in mostly Middle Eastern countries, with occasional transfer elsewhere. A key step in the MERS-CoV replication cycle is the fusion of the virus and host cell membranes mediated by the virus spike protein, S. The location of the fusion peptide within the MERS S protein has not been precisely mapped. We used isolated peptides and giant unilamellar vesicles (GUV) to demonstrate membrane binding for a peptide located near the N-terminus of the S2 domain. Key residues required for activity were mapped by amino acid replacement and their relevance in vitro tested by their introduction into recombinant MERS S protein expressed in mammalian cells. Mutations preventing membrane binding in vitro also abolished S-mediated syncytium formation consistent with the identified peptide acting as the fusion peptide for the S protein of MERS-CoV.

Progress and Prospects on Vaccine Development against SARS-CoV-2

“…The FP domain of the S2 subunit is involved in the membrane fusion of the virus, which is also a key step in viral pathogenicity [32]. Therefore, it may also serve as a vaccine candidate antigen.…”

Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein

“…Moreover, COVID-19 patients sera could strongly detect SARS-CoV S library pool S51, which partially overlaps with SARS-CoV-2 pool S21 ( Figure 1c, Supplementary Figure 1b). This region encompasses the fusion peptide, which is highly conserved among coronaviruses [10,11], suggesting a potential pan-coronavirus epitope at this location. Interestingly, targeting this region was also demonstrated to neutralize infection with a pan-coronavirus fusion inhibitor peptide [12].…”

“…A total of 25 convalescence serum samples collected during the current COVID-19 outbreak in Singapore were screened at 1:1000 dilution for neutralizing antibodies against a pseudotyped lentivirus expressing SARS-CoV-2 S glycoprotein tagged with a luciferase reporter(Figure 1a). Of the 25 patients tested, six patients(2,4,6,7,11, 20) with sufficient amount of serum samples that displayed a good neutralizing activity were selected for further functional characterization. Sera from all patients showed similar IC 50 , ranging from a titre of 694 to 836, except patient 20, who showed the strongest neutralizing activity with an IC 50 of 1603 (Figure 1b).Next, we assessed the antigenic targets of these sera using a linear B-cell peptide library spanning the entire S protein of either SARS-CoV or SARS-CoV-2 with pools of five overlapping peptides(Figure 1c, Supplementary Figure 1b).…”

Special Issue “Emerging Viruses: Surveillance, Prevention, Evolution, and Control”

“…Coronaviruses, in particular, are addressed in three papers. Kandeil et al [1] demonstrate a high seroprevalence of MERS coronavirus in adult dromedary camels from Asia and Africa, and Alsaadi et al [2] characterize a fusion peptide in the spike protein of MERS-CoV. Avian coronaviruses are also addressed in the article from Fan et al [3], which reveals the changes in genetic diversity, dominant genotypes, and selection pressure on the bronchitis virus (IBV) circulating in yellow chickens in China.…”