SARS-CoV-2 spike protein: Site-specific breakpoints for the development of COVID-19 vaccines (original) (raw)
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SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines
Journal of Translational Medicine, 2020
COVID-19 has rapidly spread all over the world, progressing into a pandemic. This situation has urgently impelled many companies and public research institutes to concentrate their efforts on research for effective therapeutics. Here, we outline the strategies and targets currently adopted in developing a vaccine against SARS-CoV-2. Based on previous evidence and experience with SARS and MERS, the primary focus has been the Spike protein, considered as the ideal target for COVID-19 immunotherapies.
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.
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.
Viruses
Inactivated vaccines are promising tools for tackling the COVID-19 pandemic. We applied several protocols for SARS-CoV-2 inactivation (by β-propiolactone, formaldehyde, and UV radiation) and examined the morphology of viral spikes, protein composition of the preparations, and their immunoreactivity in ELISA using two panels of sera collected from convalescents and people vaccinated by Sputnik V. Transmission electron microscopy (TEM) allowed us to distinguish wider flail-like spikes (supposedly the S-protein’s pre-fusion conformation) from narrower needle-like ones (the post-fusion state). While the flails were present in all preparations studied, the needles were highly abundant in the β-propiolactone-inactivated samples only. Structural proteins S, N, and M of SARS-CoV-2 were detected via mass spectrometry. Formaldehyde and UV-inactivated samples demonstrated the highest affinity/immunoreactivity against the convalescent sera, while β-propiolactone (1:2000, 36 h) and UV-inactivate...
npj Vaccines, 2020
The ‘D614G’ mutation (Aspartate-to-Glycine change at position 614) of the SARS-CoV-2 spike protein has been speculated to adversely affect the efficacy of most vaccines and countermeasures that target this glycoprotein, necessitating frequent vaccine matching. Virus neutralisation assays were performed using sera from ferrets which received two doses of the INO-4800 COVID-19 vaccine, and Australian virus isolates (VIC01, SA01 and VIC31) which either possess or lack this mutation but are otherwise comparable. Through this approach, supported by biomolecular modelling of this mutation and the commonly-associated P314L mutation in the RNA-dependent RNA polymerase, we have shown that there is no experimental evidence to support this speculation. We additionally demonstrate that the putative elastase cleavage site introduced by the D614G mutation is unlikely to be accessible to proteases.
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.
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...
American Journal of Chemistry and Pharmacy
In December 2019, a mysterious pneumonia-causing sickness frightened the world. SARS-CoV-2 caused the acute respiratory illness. Since March 11, 2020, 220,563,227 COVID-19 cases and 4,565,483 deaths have been reported worldwide as of October 2021. SARS-CoV-2, like all coronavirus, appears to have crowns due to its S proteins and enters host cells using highly glycosylated spike (S) proteins. S1 and S2 are SARS-CoV-2 spike protein subunits. S2 controls transmembrane fusion, while S1 controls receptor binding. Antibody-mediated neutralization targets SARS-CoV-2 spike (S) proteins, which are essential for viral entry and fusion. This paper summarized how S protein was used in newly created and distributed SARS-CoV-2 vaccines and the implications for future advancements given the emergence of more lethal SARS-CoV-2 variants in this paper. It also discussed the role of S protein glycosylation in the viral entry and binding mechanism of SARS-CoV-2 and the implications for developing adapt...
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.