Synthetic proteins for COVID-19 diagnostics

2022

Sci Rep

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SARS-CoV-2 has steadily mutated during its spread to > 300 million people throughout the world. The WHO has designated strains with certain mutations, “variants of concern” (VOC), as they may have higher infectivity and/or resist neutralization by antibodies in sera of vaccinated individuals and convalescent patients. Methods to detect regionally emerging VOC are needed to guide treatment and vaccine design. Cluster and network analysis was applied to over 1.2 million sequences of the SARS-CoV-2 spike protein from 36 countries in the GISAID database. While some mutations rapidly spread throughout the world, regionally specific groups of variants were identified. Strains circulating in each country contained different sets of high frequency mutations, many of which were known VOCs. Mutations within clusters increased in frequency simultaneously. Low frequency, but highly correlated mutations detected by the method could signal emerging VOCs, especially if they occur at higher frequency in other regions. An automated version of our method to find high frequency mutations in a set of SARS-COV-2 spike sequences is available online at http://curie.utmb.edu/SAR.html.

Section: Resultsmentioning

confidence: 99%

Regional and temporal coordinated mutation patterns in SARS-CoV-2 spike protein revealed by a clustering and network analysis

Negi

2022

Sci Rep

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“…Polyclonal antibodies can have overlapping binding sites even to the same peptide epitope [71, 72] and may recognize multiple similar epitopes. For example, in other experiments, we showed that polyclonal antibodies from sera of SARS-CoV-2-infected patients recognize the spike protein of the SARS-2003 virus, despite <80% sequence identity [73]. In the continuation of this alphavirus work, we will analyze the epitope specificity of the antibody ensemble produced in response to our antigens, with the goal of elevating the protective effect of the promiscuous immunogens to that of the species-specific ones against each AV.…”

Section: Discussionmentioning

confidence: 99%

Peptide and protein alphavirus antigens for broad spectrum vaccine design

Schmidt

et al. 2022

Preprint

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Vaccines based on proteins and peptides may be safer and more broad-spectrum than other approaches Physicochemical property consensus (PCPcon) alphavirus antigens from the B-domain of the E2 envelope protein were designed and synthesized recombinantly. Those based on individual species (eastern or Venezuelan equine encephalitis (EEEVcon, VEEVcon), or chikungunya (CHIKVcon) viruses generated species-specific antibodies. Peptides designed to surface exposed areas of the E2-A-domain were added to the inocula to provide neutralizing antibodies against CHIKV. EVCcon, based on the three different alphavirus species, combined with E2-A-domain peptides from AllAV, a PCPcon of 24 diverse alphavirus, generated broad spectrum antibodies. The antibodies in the sera bound and neutralized diverse alphaviruses with less than 35% amino acid identity to each other. These included VEEV and its relative Mucambo virus, EEEV and the related Madariaga virus, and CHIKV strain 181/25. Further understanding of the role of coordinated mutations in the envelope proteins may yield a single, protein and peptide vaccine against all alphaviruses.

“…For β-COVs the evolutionary path is still debated and the zoonotic origin of the SARS-CoV-2 pandemic is still being investigated. However, most observations indicate that CoVs can move from one species to another, as for example from camels to man (for MERS) and from human to mink and vice versa for SARS-CoV-2 59 , emphasizing the need for antigen based testing for animals that may be asymptomatic carriers 60 Our β-CoV PD-Graph (Figure 4) is consistent with those observations, separating the diverse strains mainly according to their receptor types and not to host types.…”

Section: Discussionmentioning

confidence: 99%

DGraph Clusters Flaviviruses and β-Coronaviruses According to Their Hosts, Disease Type, and Human Cell Receptors

Bioinform Biol Insights

2021

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Motivation: There is a need for rapid and easy-to-use, alignment-free methods to cluster large groups of protein sequence data. Commonly used phylogenetic trees based on alignments can be used to visualize only a limited number of protein sequences. DGraph, introduced here, is an application developed to generate 2-dimensional (2D) maps based on similarity scores for sequences. The program automatically calculates and graphically displays property distance (PD) scores based on physico-chemical property (PCP) similarities from an unaligned list of FASTA files. Such “PD-graphs” show the interrelatedness of the sequences, whereby clusters can reveal deeper connectivities. Results: Property distance graphs generated for flavivirus (FV), enterovirus (EV), and coronavirus (CoV) sequences from complete polyproteins or individual proteins are consistent with biological data on vector types, hosts, cellular receptors, and disease phenotypes. Property distance graphs separate the tick- from the mosquito-borne FV, cluster viruses that infect bats, camels, seabirds, and humans separately. The clusters correlate with disease phenotype. The PD method segregates the β-CoV spike proteins of severe acute respiratory syndrome (SARS), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Middle East respiratory syndrome (MERS) sequences from other human pathogenic CoV, with clustering consistent with cellular receptor usage. The graphs also suggest evolutionary relationships that may be difficult to determine with conventional bootstrapping methods that require postulating an ancestral sequence.