Immuno-informatics Characterization SARS-CoV-2 Spike Glycoprotein for Prioritization of Epitope based Multivalent Peptide Vaccine

Saba Ismail; Sajjad Ahmad; Syed Sikander Azam

In December 2019, a new strain of coronavirus emerged in Wuhan city of Hubei province in China and has since spread globally. The virus belongs to clade B of family Coronaviridae in the order Nidovirales, and genera Betacoronavirus and caused pulmonary disease outbreak [1, 2] . It is positive-sense RNA, enveloped and non-segmented virus and named as SARS-CoV-2 as it share 82% sequence identity with SARS coronavirus (SARS-CoV) [3, 4] . SARS-CoV-2 caused coronavirus disease-19 and evidence suggest a zoonotic origin of this disease [5] . Though the zoonotic transmission is not completely understood but facts provide the ground that it proliferates from the seafood market Huanan in Wuhan and human-to-human transmission resultant into the exponential increase in number of cases [6, 7] . As of March 24, 386,332 cases are reported worldwide with 16,747 deaths and 102,333 recovered patients. Among the active cases, 267,252 are currently infected, 255,166 (95%) are in mild conditions and 12,086 (5%) are seriously ill. serisouly illed. Among the 119,080 closed cases, 102,333 (86%) are recovered whereas 16,747 (14%) die. On March 11, the World Health Organization (WHO) affirmed COVID-19 as a pandemic (https://www.worldometers.info/coronavirus/). SARS-CoV-2 utilizes a highly glycosylated, homotrimeric class I viral fusion spike protein to enter into host cells [8] . This protein is found in a metastable pre-fusion state which undergoes a structural rearrangement facilitating viral membrane fusion with the host cell [9] [10] [11] . The binding of S1 subunit to a host-angiotensin-converting enzyme initiates this process and disrupts the prefusion trimeric structure resulting into S1 subunit dispersion and stabilizes the S2 subunit to a post-fusion conformation [12] . The receptor-binding domain (RBD) of S1 goes through a hingelike conformational change that temporarily hides or exposes the determinants of receptor binding in order to occupy a host-cell receptor [11] . Down and up conformation states are recognized where former is related to the receptor-inaccessible state and the later one explains receptor-accessible state and considered as less stable [13] [14] [15] [16] . This critical role of the spike protein makes it an important target for antibody-mediated neutralization, and detailed study of the pre-fusion S structure would provide information at atomic-level helping in the design and development of a vaccine [17] [18] [19] [20] [21] . Current data indicates that SARS-CoV-2 spike and SARS-CoV spike both share the same functional receptor (host cell) -angiotensin-converting enzyme 2 (ACE2) [22, 23] . Interestingly, ACE2 binds to SARS-CoV-2 spike ectodomain with ∼15 nM affinity, about 10-20 folds higher than ACE2 binding to SARS-CoV spike [24] . One possible reason for SARS-CoV-2 capability of spreading infection from human-to-human is SARS-CoV-2 spike's high affinity for human ACE2 [25] . Series of cellular immune and humoral responses can be triggered by SARS-CoV-2 infections [26] . Immunoglobulin G (IgG) and IgM were noticeable after the 2 weeks of onset of infection which are specific antibodies to SARS-CoV-2. High titers of neutralizing antibodies and SARS-CoV-2 specific cytotoxic T lymphocyte responses have been identified in the patients who have improved from SARS-CoV-2. This phenomenon clearly suggest that both cellular and humoral immune reactions are vital to clearing the SARS-CoV-2 infection [26] [27] [28] [29] [30] .