Antigenic sites in SARS-CoV-2 spike RBD show molecular similarity with pathogenic antigenic determinants and harbors peptides for vaccine development

Abstract

The spike protein of coronavirus is key target for drug development and other pharmacological interventions. In current study, we performed an integrative approach to predict antigenic sites in SARS-CoV-2 spike receptor binding domain and found nine potential antigenic sites. The predicted antigenic sites were then assessed for possible molecular similarity with other known antigens in different organisms. Out of nine sites, seven sites showed molecular similarity with 54 antigenic determinants found in twelve pathogenic bacterial species ( Mycobacterium tuberculosis, Mycobacterium leprae, Bacillus anthracis, Borrelia burgdorferi, Clostridium perfringens, Clostridium tetani, Helicobacter Pylori, Listeria monocytogenes, Staphylococcus aureus, Streptococcus pyogenes, Vibrio cholera and Yersinia pestis ), two malarial parasites ( Plasmodium falciparum and Plasmodium knowlesi ) and influenza virus A. Most of the bacterial antigens that displayed molecular similarity with antigenic sites in SARS-CoV-2 RBD (receptor binding domain) were toxins and virulent factors. Antigens from Mycobacterium that showed similarity were mainly involved in modulating host cell immune response and ensuring persistence and survival of pathogen in host cells. Presence of a large number of antigenic determinants, similar to those in highly pathogenic microorganisms, not merely accounts for complex etiology of the disease but also provides an explanation for observed pathophysiological complications, such as deregulated immune response, unleashed or dysregulated cytokine secretion (cytokine storm), multiple organ failure etc., that are more evident in aged and immune-compromised patients. Over-representation of antigenic determinants from Plasmodium and Mycobacterium in all antigenic sites suggests that anti-malarial and anti-TB drugs can prove to be clinical beneficial for COVID-19 treatment. Besides this, anti-leprosy, anti-lyme, anti-plague, anti-anthrax drugs/vaccine etc. are also expected to be beneficial in COVID-19 treatment. Moreover, individuals previously immunized/vaccinated or had previous history of malaria, tuberculosis or other disease caused by fifteen microorganisms are expected to display a considerable degree of resistance against SARS-CoV-2 infection. Out of the seven antigenic sites predicted in SARS-CoV-2, a part of two antigenic sites were also predicted as potent T-cell epitopes (KVGGNYNYL 444-452 and SVLYNSASF 366-374 ) against MHC class I and three (KRISNCVADYSVLYN 356-370 , DLCFTNVYADSFVI 389-402 , and YRVVVLSFELLHA 508-520 ) against MHC class II. All epitopes possessed significantly lower predicted IC50 value which is a prerequisite for a preferred vaccine candidate for COVID-19.

The Pandemic Experience in Southeast Asia: Interface Between SARS-CoV-2, Malaria, and Dengue

“…Additionally, there may be shared epitopes between SARS-CoV-2 and Plasmodium spp. that could further explain production of cross-reactive antibodies (65)(66)(67), though these appear to be non-functional (43).…”

Maternal COVID-19 Vaccination and Its Potential Impact on Fetal and Neonatal Development

“…This supports Classen's concern that COVID-19 vaccines could potentially induce prion disease [82]. The third region of interest within the RBD contains seven predicted molecular sites that share similarities to different toxins or virulence factors from 12 different bacterial species, 2 malarial parasites and influenza A [83] (Figure 1).…”

Recombinant COVID-19 vaccine based on recombinant RBD/Nucleoprotein and saponin adjuvant induces long-lasting neutralizing antibodies and cellular immunity

“…Lymphocyte proliferation of splenocytes was evaluated (three mice/group) one week after the last vaccination. The splenocytes at a concentration of 2 × 10 5 cells/well were propagated in the 96 well plates containing RPMI-1640 supplemented with 10% FBS, 1% L-glutamine, 1% HEPES, and 0.1% penicillin/streptomycin in the presence of 1μg of synthetic RBD (366-374aa)/N (223-231aa)-specific CTL epitope (Biomatik, Canada) ( 24 – 27 ) or culture media as mock stimulated control.…”