Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies

Ahmed, Syed Faraz; Quadeer, Ahmed Abdul; McKay, Matthew R.

doi:10.3390/v12030254

Cited by 1,053 publications

(972 citation statements)

References 50 publications

(75 reference statements)

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“…This shortlist of peptides is proposed by the authors for experimental validation. Another relevant paper was published by Ahmed et al [18], who combined experimental, in silico and populational approaches. Based on previous knowl-edge, the authors first identified experimentally determined SARS-CoV-1 derived T cell epitopes in the immunogenic structural spike (S) and nucleocapsid (N) proteins of SARS-CoV-1 that were associated with positive T cell or HLA binding assays, based on the high genetic similarity between the two viruses.…”

Section: Bioinformatic and Experimental Studiesmentioning

confidence: 99%

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HLA studies in the context of coronavirus outbreaks

Sanchez‐Mazas¹

2020

Swiss Med Wkly

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The unique health situation that we humans are currently living in at the global scale due to the COVID-19 pandemic urges scientists to gain maximum understanding about the characteristics of the new SARS-CoV-2 coronavirus, the way it contaminates individuals, and the genetic and non-genetic factors that influence our susceptibility or protection to its too often severe consequences. Little is known at the moment about specific immune mechanisms that would work against SARS-CoV-2, although such knowledge is expected to play a vital role in the absence of efficient drugs and vaccines, as is the case today. In this context, a particular focus has to be given to the human leucocyte antigen (HLA) system that governs our adaptive immunity.HLA genes are known to display the highest level of diversity of our genome, with thousands of different alleles reported nowadays, each allele being also a combination of multiple single nucleotide polymorphisms (SNPs). This unique level of polymorphism likely results from thousands of generations (since the emergence of modern humans) of HLA molecular evolution where natural selection favoured genetic variation, balancing selection in the form of heterozygous advantage (in its different versions) being the most widely accepted model. The idea of such a model is that heterozygous individuals would display a higher fitness than homozygotes in pathogen-rich environments, different HLA molecules assuming complementary abilities to present pathogen-derived peptides to T cells and elicit an immune response. The consequence of this kind of selection, at the population level, is that HLA allele frequency distributions are more even than expected under neutral evolution, most human populations displaying between 85% and 95% heterozygosity at each HLA locus.

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Section: Bioinformatic and Experimental Studiesmentioning

confidence: 99%

“…Ahmed et al 2020 [18] SARS-CoV-2 Peptide-binding and immunogenetic predictions for SARS-CoV-2 derived peptides and population coverage analysis of the associated HLA alleles.…”

Section: Virus Bioinformatic Approach Experimental Approach Main Concmentioning

confidence: 99%

HLA studies in the context of coronavirus outbreaks

Sanchez‐Mazas¹

2020

Swiss Med Wkly

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“…Specifically, we have extensively studied the free energies and dynamics of RBD-ACE2 binding, spike protein, and free RBD protein systems. Given that the spike protein is not only a potential drug target but also the virus antigen [35], the present study will be beneficial for the drug design, vaccine development, and disease prevention of SARS-CoV-2.…”

mentioning

confidence: 99%

Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2

Tao

Yan

et al. 2020

Viruses

159

190

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The outbreak of a novel coronavirus, which was later formally named the severe acute respiratory coronavirus 2 (SARS-CoV-2), has caused a worldwide public health crisis. Previous studies showed that SARS-CoV-2 is highly homologous to SARS-CoV and infects humans through the binding of the spike protein to ACE2. Here, we have systematically studied the molecular mechanisms of human infection with SARS-CoV-2 and SARS-CoV by protein-protein docking and MD simulations. It was found that SARS-CoV-2 binds ACE2 with a higher affinity than SARS-CoV, which may partly explain that SARS-CoV-2 is much more infectious than SARS-CoV. In addition, the spike protein of SARS-CoV-2 has a significantly lower free energy than that of SARS-CoV, suggesting that SARS-CoV-2 is more stable and may survive a higher temperature than SARS-CoV. This provides insights into the evolution of SARS-CoV-2 because SARS-like coronaviruses have originated in bats. Our computation also suggested that the RBD-ACE2 binding for SARS-CoV-2 is much more temperature-sensitive than that for SARS-CoV. Thus, it is expected that SARS-CoV-2 would decrease its infection ability much faster than SARS-CoV when the temperature rises. These findings would be beneficial for the disease prevention and drug/vaccine development of SARS-CoV-2.Viruses 2020, 12, 428 2 of 11 origin and is 96% identical at the whole-genome level to a bat SARS-like coronavirus [22]. In addition, SARS-CoV-2 is also closely related to other SARS-like coronaviruses and shares a 79.5% sequence identity to SARS-CoV [22]. For some encoded proteins like coronavirus main proteinase (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp), the sequence identity is even higher and can be as high as 96% between SARS-CoV-2 and SARS-CoV [23]. Therefore, it was thought that SARS-CoV-2 would function in a similar way to SARS-CoV in the human-infection and pathogenic mechanism [22][23][24].Coronaviruses use the surface spike (S) glycoprotein on the coronavirus envelope to attach host cells and mediate host cell membrane and viral membrane fusion during infection [25]. The spike protein includes two regions, S1 and S2, where S1 is for host cell receptor binding and S2 is for membrane fusion. The S1 region also includes an N-terminal domain (NTD) and three C-terminal domains (CTD1, CTD2, and CTD3) [26]. For SARS-CoV, the receptor binding domain (RBD) is located in the CTD1 of the S1 region. SARS-CoV attaches the human host cells through the binding of the RBD protein to the angiotensin-converting enzyme II (ACE2) [27,28]. Therefore, the interaction between RBD and ACE2 is a prerequisite for the human infection with SARS-CoV. Given the high homology between SARS-CoV and SARS-CoV-2, it was expected that SARS-CoV-2 would also use the ACE2 molecule as the receptor to enter human cells [24,29]. This hypothesis was further experimentally confirmed by the virus infectivity studies from the Shi group, in which SARS-CoV-2 is able to use the ACE2 proteins from humans, Chinese horseshoe bats, and civ...

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“…At the same time, already at the preclinical level, the administered vaccines based on the administration of the entire SARS-CoV-2 spike protein ( (56)(57)(58) or on the administration of the single SARS-CoV-2 spike RBD, will induce the production of specific antibodies that might be sequenced and modelled in silico. On this concern, the provided molecular network will help in quantifying interactions between SARS-CoV-2 RBD (also in cases of different RBD variants (86)) and the newly investigated antibodies, i.e.lower the calculated binding energy in the modelled complex, higher the likelihood to have more success with the investigated vaccines/antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…understanding virus invasion mechanisms, developing new vaccines or antibodies, identifying small molecules with high affinity for viral proteins and establishing quick/safe diagnosis selective/specific kits. Indeed, the scientific community is now focused in the development of new weapons for containing SARS-CoV-2 spread and COVID-19 complications as it could be observed in the enormous effort in developing new vaccines based on a virus protein/nucleic acid portion able to induce an efficient and specific immunogenic response(56)(57)(58)(59)(60), or in developing a neutralizing antibody highly specific for SARS-CoV-2 spike RBD(25,26,(61)(62)(63)(64), or in identifying chemicals with high affinity for SARS-CoV-2 crucial proteins (1-3, 65-67).…”

mentioning

confidence: 99%

Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies

Mercurio

Tragni

Busco

et al. 2020

Preprint

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Abbreviations: Severe acute respiratory syndrome, SARS; coronavirus CoV; receptor binding domain, RBD; angiotensin converting enzyme 2, ACE2; fragment antigen binding, FAB; Word Health Organizzation, WHO; complementary-determining regions, (CDR); SwissPDBViewer, SPDBV. ABSTRACT The recent severe acute respiratory syndrome, known as Corona Virus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim we performed an in silico comparative modeling analysis, which allows to gain new insights about the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor binding domain (RBD), along interactions with human cells angiotensin converting enzyme 2 (ACE2) receptor, that favour human cell invasion. Furthermore, our analysis provides i) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, for preventing interactions with the human ACE2, and ii) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico a high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high affinity antibodies against present and future coronavirus able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnosis kits and other treatments based on the usage or the targeting of SARS-CoV-2 spike protein.

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Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies

Cited by 1,053 publications

References 50 publications

HLA studies in the context of coronavirus outbreaks

HLA studies in the context of coronavirus outbreaks

Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2

Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies

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