Common low complexity regions for SARS-CoV-2 and human proteomes as potential multidirectional risk factor in vaccine development

Gruca, Aleksandra; Ziemska-Legięcka, Joanna; Jarnot, Patryk; Sarnowska, Elżbieta; Sarnowski, Tadeusz; Grynberg, Marcin

doi:10.1101/2020.08.11.245993

Cited by 3 publications

(6 citation statements)

References 103 publications

(90 reference statements)

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“…NSP3a can be classified as a “low complexity region”, found in many viruses, including Coronaviridae. Such regions are considered to be highly immunogenic and, importantly, they share high simmilarity with human epitopes, thus making them a risk for antiviral drug or testing development [44]. The enrichment of glutamic acid was found as a feature of the highly immunogenic polypeptides, in other organisms as well [45].…”

Section: Discussionmentioning

confidence: 99%

Analysis of genome characteristics and transmission of SARS-CoV-2 strains in North-East of Romania during the first COVID-19 outbreak

Lobiuc

Dimian

Puscaselu

et al. 2020

Preprint

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Romania officially declared its first SARS-CoV-2 case on February 26, 2020. The first and largest COVID-19 outbreak in Romania was recorded in Suceava, N/E region of the country, and originated at the Suceava regional county hospital. Following sheltering-in-place measures, infection rates decreased, only to rise again after relaxation of measures. This study describes the incursion of SARS-CoV-2 in Suceava and other parts of Romania and analyzes the mutations and their association with clinical manifestation of the disease during the period of COVID-19 outbreak. Phylogenetic analysis indicated multiple sites of origin for SARS-CoV-2 strains in Suceava, specifically from Spain, Italy and Russia, but also other strains related to those from Czech Republic, Belgium and France. Most Suceava samples contained mutations common to European lineages, such as A20268G, however aproximately 10% of samples were missing such mutations, indicating a possible different origin. While overall genome regions ORF1ab, S and ORF7 were subject to most mutations, several recurring mutations such as C27707T were identified, and these were mainly present in severe forms of the disease. Non-synonymous mutations, such as C3225A (Thr987Asn in NSP3a domain), associated with changes in a protein responsible for decreasing viral tethering in human host were also present. Patients with diabetes and hypertension exhibited eight and three time,s respectively, higher odds ratios of acquiring severe forms of the disease and these were mainly related to C27707T mutation. These results will aid in tracing virus movement throughout Romania and identification of infectivity, virulence and pathogenicity.

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Section: Discussionmentioning

confidence: 99%

Analysis of genome characteristics and transmission of SARS-CoV-2 strains in North-East of Romania during the first COVID-19 outbreak

Lobiuc

Dimian

Puscaselu

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…NSP3a can be classified as a "low complexity region, " found in many viruses, including Coronaviridae. Such regions are considered to be highly immunogenic and, importantly, they share high similarity with human epitopes, thus placing them a risk for antiviral drug or testing development (Gruca et al, 2020). The enrichment of glutamic acid was found as a feature of the highly immunogenic polypeptides, in other organisms as well (Hou et al, 2020).…”

Section: Viral Protein Modificationsmentioning

confidence: 99%

Introduction and Characteristics of SARS-CoV-2 in North-East of Romania During the First COVID-19 Outbreak

et al. 2021

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Romania officially declared its first Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) case on February 26, 2020. The first and largest coronavirus disease 2019 (COVID-19) outbreak in Romania was recorded in Suceava, North-East region of the country, and originated at the Suceava regional county hospital. Following sheltering-in-place measures, infection rates decreased, only to rise again after relaxation of measures. This study describes the spread of SARS-CoV-2 in Suceava and other parts of Romania and analyses the mutations and their association with clinical manifestation of the disease during the period of COVID-19 outbreak. Sixty-two samples were sequenced via high-throughput platform and screened for variants. For selected mutations, putative biological significance was assessed, and their effects on disease severity. Phylogenetic analysis was conducted on Romanian genomes (n = 112) and on sequences originating from Europe, United Kingdom, Africa, Asia, South, and North America (n = 876). The results indicated multiple introduction events for SARS-CoV-2 in Suceava, mainly from Italy, Spain, United Kingdom, and Russia although some sequences were also related to those from the Czechia, Belgium, and France. Most Suceava genomes contained mutations common to European lineages, such as A20268G, however, approximately 10% of samples were missing such mutations, indicating a possible different arrival route. While overall genome regions ORF1ab, S, and ORF7 were subject to most mutations, several recurring mutations such as A105V were identified, and these were mainly present in severe forms of the disease. Non-synonymous mutations, such as T987N (Thr987Asn in NSP3a domain), associated with changes in a protein responsible for decreasing viral tethering in human host were also present. Patients with diabetes and hypertension exhibited higher risk ratios (RR) of acquiring severe forms of the disease and these were mainly related to A105V mutation. This study identified the arrival routes of SARS-CoV-2 in Romania and revealed potential associations between the SARS-CoV-2 genomic organization circulating in the country and the clinical manifestation of COVID-19 disease.

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“…Given the immunological signi cance of pathogens' surface proteins in which many LCRs are located 6,7,9 , it is somewhat surprising that little attention has been given to their presence in viral proteomes. In sensu stricto, the presence and location of LCRs has only been reported in the HIV-1 8 and, more recently, in SARS-CoV-2 10 . They are rather abundant in the HIV-1 gp120 protein, and over 30% of them are located in the hypervariable regions of the connecting loops present in the protein, where they probably play a role in immune escape 8 .…”

Section: Introductionmentioning

confidence: 99%

“…They are rather abundant in the HIV-1 gp120 protein, and over 30% of them are located in the hypervariable regions of the connecting loops present in the protein, where they probably play a role in immune escape 8 . LCRs are scattered throughout the SARS-CoV-2 proteome, but are conspicuously absent in some proteins of the replication-transcription complex (RdRp, helicase, and NSP14 exonuclease), and in the NSP1, 3CL protease, NSP9-11, NSP15, ORF3a, membrane (M) protein, ORF6, ORF8 and ORF10 proteins 10 . This indicates that these proteins are under strong purifying selection, and that any compositional change is rapidly selected against.…”

Section: Introductionmentioning

confidence: 99%

“…This indicates that these proteins are under strong purifying selection, and that any compositional change is rapidly selected against. In SARS-CoV-2 LCRs are more prevalent in the nonstructural protein 3, spike protein, and the nucleocapsid protein, where they may simultaneously enhance immune evasion and induce a strong immunogenic response 10 .…”

Section: Introductionmentioning

confidence: 99%

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Two Short Low Complexity Regions (LCRs) are Hallmark Sequences of the Delta SARS-CoV- 2 Variant Spike Protein

Becerra

Muñoz-Velasco

Aguilar-Cámara

et al. 2021

Preprint

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Low complexity regions (LCRs) are protein sequences formed by a set of compositionally biased residues. LCRs are extremely abundant in cellular proteins and have also been reported in viruses, where they may partake in evasion of the host immune system. Here we report four novel extremely conserved LCRs in the spike proteins of several SARS-CoV-2 variants. With the exception of Iota, where it is absent, the Spike LCR-1 is present in the signal peptide of 80.57% of the Delta variant, and in other variants of concern and interest. The Spike LCR-2 is highly prevalent (79.87%) in Iota. Two distinctive LCRs are present in the Delta spike protein. The Delta Spike LCR-3 is present in 99.19% of the analyzed sequences, and the Delta Spike LCR-4 in 98.3% of the same set of proteins. These two LCRs are present in the furin cleavage site and HR1 domain, respectively, and may be considered hallmark traits of the Delta variant. The presence of two medically-important point mutations, P681R and D950N, in these LCRs, combined with the extraordinary conservation of these regions, suggests that they may be a trait associated with the rapid spread of the highly contagious Delta lineage.

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Common low complexity regions for SARS-CoV-2 and human proteomes as potential multidirectional risk factor in vaccine development

Cited by 3 publications

References 103 publications

Analysis of genome characteristics and transmission of SARS-CoV-2 strains in North-East of Romania during the first COVID-19 outbreak

Analysis of genome characteristics and transmission of SARS-CoV-2 strains in North-East of Romania during the first COVID-19 outbreak

Introduction and Characteristics of SARS-CoV-2 in North-East of Romania During the First COVID-19 Outbreak

Two Short Low Complexity Regions (LCRs) are Hallmark Sequences of the Delta SARS-CoV- 2 Variant Spike Protein

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