A Putative Prophylactic Solution for COVID-19: Development of Novel Multiepitope Vaccine Candidate against SARS‐COV‐2 by Comprehensive Immunoinformatic and Molecular Modelling Approach

Abstract

The outbreak of 2019-novel coronavirus (SARS-CoV-2) that causes severe respiratory infection (COVID-19) has spread in China, and the world health organization declared it pandemic. However, no approved drug or vaccines are available, and treatment is mainly supportive and through a few repurposed drugs. In this urgency situation, development of SARS-CoV-2 based vaccines is immediately required. Immunoinformatic and molecular modelling are generally used time-efficient methods to accelerate the discovery and design of the candidate peptides for vaccine development. In recent years, the use of multiepitope vaccines is proved to be a promising immunization strategy against viruses and pathogens, which induce more comprehensive protective immunity. The current study demonstrated a comprehensive in-silico strategy to design stable multiepitope vaccine construct (MVC) from B-cell and T-cell epitopes of essential SARS-CoV-2 proteins with the help of adjuvants and linkers. The integrated molecular dynamics simulations analysis revealed the stability of MVC and its interaction with human Toll-like receptors (TLRs), which trigger an innate and adaptive immune response. Later, the in-silico cloning in a known pET28a vector system also estimated the possibility of MVC expression in E. Coli. Despite this study lacks validation of this vaccine construct in terms of its efficacy, the current integrated strategy encompasses the initial multiple epitope vaccine design concepts. After validation, this MVC can present to be a better prophylactic solution against COVID-19.

A Candidate multi-epitope vaccine against SARS-CoV-2

“…Generally, a protein whose instability index is lesser than 40 are predicted to be stable and values above that predicts the protein as unstable [55]. The stability of the vaccine candidate in this study was found to be better than the recently published multiepitope vaccine candidate against SARS-CoV-2 in which instability index was found higher than the vaccine candidate of this study [56,57]. The theoretical pI of the vaccine was calculated to be 9.96.…”

Immunoinformatics and molecular modeling approach to design universal multi-epitope vaccine for SARS-CoV-2

“…Though a research group has recently conducted a study like us, it never considered accessory proteins for probable vaccine construction. Rather, the have designed a multi-epitope vaccine from four proteins (Spike, Mpro, RdRp, and Nsp13) of SARS-CoV-2 which showed a lower antigenicity score (0.4259) [ 93 ] when compared to our study.…”

Multi-epitope vaccine against SARS-CoV-2 applying immunoinformatics and molecular dynamics simulation approaches

“…For instance, spike glycoprotein of SARS-CoV-2 has been evaluated extensively to design different multi-epitope vaccines (Abraham Peele et al., 2020 ; Kar et al., 2020 , Samad et al., 2020 ). Additionally, spike protein has also been used in combination of epitopes from other viral proteins including nucleocapsid and membrane (Kalita et al., 2020 ), protein 8 (Nsp8) and 3 C-like proteinase (Ahmad et al., 2020 ), main protease, Nsp12 (polymerase) and Nsp13 (helicase) (Rehman et al., 2020 ) for construction of peptide-based vaccines. These vaccine candidates were found to be antigenic, non-allergenic and stable in nature, but presence of additional epitopes from other region of S protein or other viral proteins might result into excessive antigenic load along with increased chances of allergenic response.…”