The Potential of Developing Pan-Coronaviral Antibodies to Spike Peptides in Convalescent COVID-19 Patients

Abstract

Coronaviruses share conservative spike protein (S) on their enveloped membrane surface, where S1 subunit recognizes and binds the cellular receptor, and the S2 subunit mediates membrane fusion. This similarity raises the question: does coronaviral infection by one create protection to others? Convalescent SARS-CoV-2 (COVID-19) sera were tested for cross reactivity with peptides from Middle East respiratory syndrome coronavirus (MERS-CoV) which shares 74% homology. Our results showed significant cross-reactivity with a peptide of the heptad repeat 2 (HR2) domain of the MERS-CoV spike protein. Sera samples of 47 validated seropositive convalescent COVID-19 patients and 40 sera samples of control patients, collected in pre-COVID time were used to establish cross-bind reactivity with the MERS-CoV peptide. Significantly stronger binding (p < 0.0001) was observed for IgG antibodies in convalescent COVID-19 patients compared to the control group. In ELISA, MERS-CoV peptide helps to discriminate post-COVID-19 populations and non-infected ones by the presence of antibodies in blood samples. This suggests that polyclonal antibodies established during SARS-CoV-2 infection can recognize and probably decrease severity of MERS-CoV and other coronaviral infections. The high homology of the spike protein domain also suggests that the opposite effect can be true: coronaviral infections produce cross-reactive antibodies effective against SARS-CoV-2. The collected data prove that despite the core HR2 region is hidden in the native viral conformation, its exposure during cell entry makes it highly immunogenic. Since inhibitory peptides to this region were previously described, this opens new possibilities in fighting coronaviral infections and developing vaccines effective even after possible viral mutations.

Keywords: Antibodies; COVID-9; Coronavirus; Immunoglobulins; SARS-CoV-2.

Fig. 1

Similarity of HR2 regions between different coronaviruses. a Image of Spike protein (S1) of SARS-CoV-2. b S1 upon host cell interaction: conformational changes in trimer are occurring, exposing previously hidden HR2 domain regions (Wrapp et al. 2020), c monomeric part of (b), exposing domain with structural similarity (yellow—identical, orange—similar amino acids) towards corresponding MERS peptide, depicted on (d) and pan. (f). Protein BLAST analysis of used MERS protein is showing similarity towards the sequence in the genome of SARS-CoV-19. Sequence ID: QKJ68605.1. Crystal structure of HR2 domain for SARS-CoV-2 is currently not available, thus it is represented as a rectangle in (a) based on the last connected coordinates available in 6VSB structure

Fig. 2

Antibody cross-reactivity between coronaviruses: sera of convalescent COVID-19 patients possess antibodies recognizing MERS-specific peptide of HR2 spike protein domain. a Difference between IgG levels recognizing peptide of HR2 domain in S protein of MERS in convalescent SARS-CoV-2 patients and non-infected healthy donors. b ROC curve for discrimination of “anti-coronaviral” IgG antibodies using indicated MERS peptide as antigen. c IgG reactivity in convalescent plasma of SARS-CoV-2 patients towards HR2 domain in S protein of MERS vs RBD part of S protein of SARS-CoV-2. ****p < 0.0001