SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines (original) (raw)
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International Journal of Pathogen Research, 2020
In time past, to date combating against diseases and fatal disorders (of known or idiopathic cause) is a major effort among the human race. The emergence of several, novel and pathogenic viral infections have posed a great threat to humanity and could wipe us out of existence if there are no counter measures. Among the increasing number of pathogenic viruses in this past decade, the advent of the recent imperial SARS-CoV-2 coronavirus type cannot be underestimated as it is not just a malady endemic to a nation, but have also triggered an emergency of public health across the globe. SARS-CoV-2 a memorial of the initial Severe Acute Respiratory Syndrome (SARS) reported in China in (2003) is the etiological agent of the mysterious COVID-19 reported to originate from Wuhan, Hubei province, China in 2019. Though the virus exhibit mild pathogenicity compared to other previously emerged human coronaviruses (HCoV-OC43, HCoV-HKU1, MERS-CoV, and SARS-CoV), however, the high transmissibility and infectivity among human is alarming. In spite the evidences from the increasing number of substantiated global cases and deaths resulting from the epidemic outbreak to date, curative measures to curtail and treat this disease are still lacking. Just like SARS-CoV, it has been revealed that SARS-CoV-2 also uses similar receptor for infectivity and shares similar disease pathogenesis. This knowledge presents a therapeutic target against COVID-19. The presence of cross-reactive epitopes in the spike protein subunit of SARS-CoV and SARS-CoV-2 present the use of neutralization antibodies from convalescent SARS challenged patients against COVID 19. However, limited cross-neutralization due to lower sequence conservation in the Spike protein subunit could render this approach ineffective. Realizing the urgent need for developing potent therapeutics against the imminent risk of COVID-19 on humanity, this review article, suggests the use of SARS-CoV-2 recombinant Spike protein-based vaccine as an immunotherapeutic target to combat COVID-19 based on garnered knowledge from researches on consanguineal coronaviruses (SARS-CoV, and MERS-CoV), and current trends in vaccine development against this infection.
Immune Epitopes of SARS-CoV-2 Spike Protein and Considerations for Universal Vaccine Development
Despite the success of global vaccination programs in slowing the spread of COVID-19, these efforts have been hindered by the emergence of new SARS-CoV-2 strains capable of evading prior immunity. The mutation and evolution of SARS-CoV-2 have created a demand for persistent efforts in vaccine development. SARS-CoV-2 Spike protein has been the primary target for COVID-19 vaccine development, but it is also the hotspot of mutations directly involved in host susceptibility and immune evasion. Our ability to predict emerging mutants and select conserved epitopes is critical for the development of a broadly neutralizing therapy or a universal vaccine. In this article, we review the general paradigm of immune responses to COVID-19 vaccines, highlighting the immunological epitopes of Spike protein that are likely associated with eliciting protective immunity resulting from vaccination. Specifically, we analyze the structural and evolutionary characteristics of the SARS-CoV-2 Spike protein ...
Prospect of SARS-CoV-2 spike protein: Potential role in vaccine and therapeutic development
Virus Research
The recent outbreak of the betacoronavirus SARS-CoV-2 has become a significant concern to public health care worldwide. As of August 19, 2020, more than 22,140,472 people are infected, and over 781,135 people have died due to this deadly virus. In the USA alone, over 5,482,602 people are currently infected, and more than 171,823 people have died. SARS-CoV-2 has shown a higher infectivity rate and a more extended incubation period as compared to previous coronaviruses. SARS-CoV-2 binds much more strongly than SARS-CoV to the same host receptor, angiotensin-converting enzyme 2 (ACE2). Previously, several methods to develop a vaccine against SARS-CoV or MERS-CoV have been tried with limited success. Since SARS-CoV-2 uses the spike (S) protein for entry to the host cell, it is one of the most preferred targets for making vaccines or therapeutics against SARS-CoV-2. In this review, we have summarised the characteristics of the S protein, as well as the different approaches being used for the development of vaccines and/or therapeutics based on the S protein.
2021
Recombinant protein approaches offer major promise for safe and effective vaccine prevention of SARS-CoV-2 infection. We developed a recombinant spike protein vaccine (called NARUVAX-C19) and characterized its ability when formulated with a nanoemulsion adjuvant to induce anti-spike antibody and T-cell responses and provide protection including against viral transmission in rodent. In mice, NARUVAX-C19 vaccine administered intramuscularly twice at 21-day interval elicited balanced Th1/Th2 humoral and T-cell responses with high titers of neutralizing antibodies against wild-type (D614G) and delta (B.1.617.2) variants. In Syrian hamsters, NARUVAX-C19 provided complete protection against wild-type (D614G) infection and prevented its transmission to naïve animals placed in the same cage as challenged animals. The results contrasted with only weak protection seen with a monomeric spike receptor binding domain (RBD) vaccine even when formulated with the same adjuvant. These encouraging re...
SARS-CoV-2 spike protein: pathogenesis, vaccines, and potential therapies
Infection
Purpose COVID-19 pandemic has emerged as a result of infection by the deadly pathogenic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causing enormous threats to humans. Coronaviruses are distinguished by a clove-like spike (S) protein, which plays a key role in viral pathogenesis, evolutions, and transmission. The objectives of this study are to investigate the distinctive structural features of SARS-CoV-2 S protein, its essential role in pathogenesis, and its use in the development of potential therapies and vaccines. Methodology A literature review was conducted to summarize, analyze, and interpret the available scientific data related to SARS-CoV-2 S protein in terms of characteristics, vaccines development and potential therapies. Results The data indicate that S protein subunits and their variable conformational states significantly affect the virus pathogenesis, infectivity, and evolutionary mutation. A considerable number of potential natural and synthetic therapies were proposed based on S protein. Additionally, neutralizing antibodies were recently approved for emergency use. Furthermore, several vaccines utilizing the S protein were developed. Conclusion A better understanding of S protein features, structure and mutations facilitate the recognition of the importance of SARS-CoV-2 S protein in viral infection, as well as the development of therapies and vaccines. The efficacy and safety of these therapeutic compounds and vaccines are still controversial. However, they may potentially reduce or prevent SARS-CoV-2 infection, leading to a significant reduction of the global health burden of this pandemic.
SARS-CoV-2 spike protein: Site-specific breakpoints for the development of COVID-19 vaccines
Journal of King Saud University - Science, 2021
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Spike protein of SARS-CoV-2 variants: a brief review and practical implications
Brazilian Journal of Microbiology
The scientific community has been alarmed by the possible immunological evasion, higher infectivity, and severity of disease caused by the newest variants of SARS-CoV-2. The spike protein has an important role in the cellular invasion of viruses and is the target of several vaccines and therapeutic resources, such as monoclonal antibodies. In addition, some of the most relevant mutations in the different variants are on the spike (S) protein gene sequence that leads to structural alterations in the predicted protein, thus causing concern about the protection mediated by vaccines against these new strains. The present review highlights the most recent knowledge about COVID-19 and vaccines, emphasizing the different spike protein structures of SARS-CoV-2 and updating the reader about the emerging viral variants and their classifications, the more common viral mutations described and their distribution in Brazil. It also compiles a table with the most recent knowledge about all of the Omicron spike mutations.
Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design
Viruses
The spike protein in SARS-CoV-2 (SARS-2-S) interacts with the human ACE2 receptor to gain entry into a cell to initiate infection. Both Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273 vaccine candidates are based on stabilized mRNA encoding prefusion SARS-2-S that can be produced after the mRNA is delivered into the human cell and translated. SARS-2-S is cleaved into S1 and S2 subunits, with S1 serving the function of receptor-binding and S2 serving the function of membrane fusion. Here, I dissect in detail the various domains of SARS-2-S and their functions discovered through a variety of different experimental and theoretical approaches to build a foundation for a comprehensive mechanistic understanding of how SARS-2-S works to achieve its function of mediating cell entry and subsequent cell-to-cell transmission. The integration of structure and function of SARS-2-S in this review should enhance our understanding of the dynamic processes involving receptor binding, multiple cle...
The Future of the COVID-19 Pandemic: How Good (or Bad) Can the SARS-CoV2 Spike Protein Get?
Cells, 2022
Severe acute respiratory syndrome virus 2 (SARS-CoV2) has infected an estimated 400 million people world-wide, causing approximately 6 million deaths from severe coronavirus disease 2019 (COVID-19). The SARS-CoV2 Spike protein plays a critical role in viral attachment and entry into host cells. The recent emergence of highly transmissible variants of SARS-CoV2 has been linked to mutations in Spike. This review provides an overview of the structure and function of Spike and describes the factors that impact Spike’s ability to mediate viral infection as well as the potential limits to how good (or bad) Spike protein can become. Proposed here is a framework that considers the processes of Spike-mediated SARS-CoV2 attachment, dissociation, and cell entry where the role of Spike, from the standpoint of the virus, is to maximize cell entry with each viral-cell collision. Key parameters are identified that will be needed to develop models to identify mechanisms that new Spike variants migh...
Introduction: The rampant widespread of COVID-19 crossing continents in the year 2020 is primarily because of its unique spike protein architecture. Hence, the spike protein sequence similarities among the representatives of coronaviruses were evaluated so as to arrive at possible conservancy in its epitopes. Methods: Multiple sequence alignment and molecular phylogenetic analysis were done using MEGA software version X. Clustal omega open software was adapted to develop Percent Identity Matrix of spike proteins. Online IEDB tools were used to explore linear epitopes within the RBD region of spike protein of SARS CoV2 isolate of Wuhan-Hu-1 and their conservancy across the species of the chosen CoVs. Results: The constructed phylogenetic tree showed a primary cluster between SARS CoV2s of Wuhan and Bangladesh strains. The branch length of this primary cluster reflected their recency in emergence. Further, this primary cluster developed as an offshoot of yet another primary cluster between SARS CoV and bat SARS CoV. All betacoronaviruses grouped as one tertiary cluster, wherein MERS CoV formed as an independent offshoot and its branch length reflected that it is phylogenetically older. Both SARS CoV2s are the closest relatives to SARS CoV and Bat SARS CoV of China, and hence the similar pattern was confirmed through MEGA analysis. Ten linear epitopes were identified within the RBD region of the spike protein for the population of the State of Andhra Pradesh among Indian Asians based on their HLA haplotype diversity. Further, Conservancy Analysis of spike protein suggested that SARS CoV2 and SARS CoV shared 53% predicted epitopes. The physicochemical features of the envisaged polytope indicated the presence of 12.96% charged residues with instability index showing stable nature and more hydrophilicity as revealed through GRAVY values indicating that residues of polytope possibly interact well in aqueous environment. The secondary structure of the envisaged polytope showed predominantly coils, moderate number beta pleated sheets and α-helices with 41.2% residues in favoured region and 44.7% in allowed regions of Ramachandran Plot. Conclusion: The derived predicted scores of T-cell and B-cell immunogenicity, MHC class I binding, non-toxic and non-allergic due to the identified multi-epitope confirmed to be antigenic and elicit both T-cell and B-cell immune responses. Population coverage tool (IEDB) showed an adequate fraction of individuals predicted to respond to a given set of identified epitopes with known MHC restrictions in Indian Asian population.