A deletion in SARS‐CoV‐2 ORF7 identified in COVID‐19 outbreak in Uruguay

Panzera, Yanina; Ramos, Natália; Frabasile, Sandra; Calleros, Lucía; Marandino, Ana; Tomás, Gonzalo; Techera, Claudia; Grecco, Sofía; Fuques, Eddie; Goñi, Natalia; Ramas, Viviana; Cóppola, Leticia; Chiparelli, Héctor; Sorhouet, Cecilia; Mogdasy, Cristina; Arbiza, Juan; Delfraro, Adriana; Pérez, Ruben

doi:10.1111/tbed.14002

Cited by 26 publications

(28 citation statements)

References 39 publications

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“…The deletions within the ORF7a and ORF7b region have also previously been reported [ 15 - 18 ]. ORF7a activates the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) pathway and induces proinflammatory cytokine expression [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 63%

Expansion of a SARS-CoV-2 Delta variant with an 872 nt deletion encompassing ORF7a, ORF7b and ORF8, Poland, July to August 2021

et al. 2021

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Routine genomic surveillance on samples from COVID-19 patients collected in Poland during summer 2021 revealed the emergence of a SARS-CoV-2 Delta variant with a large 872 nt deletion. This change, confirmed by Sanger and deep sequencing, causes complete loss of ORF7a, ORF7b, and ORF8 genes. The index case carrying the deletion is unknown. The standard pipeline for sequencing may mask this deletion with a long stretch of N’s. Effects of this deletion on phenotype or immune evasion needs further study.

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Section: Discussionmentioning

confidence: 63%

Expansion of a SARS-CoV-2 Delta variant with an 872 nt deletion encompassing ORF7a, ORF7b and ORF8, Poland, July to August 2021

et al. 2021

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“…SARS-CoV-2 ORF7a is also linked to viral transmission and pathogenesis through inhibition of interferon signaling [ 13 , 14 ]. Several studies have reported deletions in the ORF7a gene in SARS-CoV-2 isolates, but were unable to place them in the clinical context [ 15 , 16 , 17 , 18 , 19 ]. However, in vitro deletion of ORF7a gene reduces replication of the synthetic virus [ 20 ], suggesting an important role of ORF7a in disease severity.…”

Section: Introductionmentioning

confidence: 99%

A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19

Lobiuc

Șterbuleac

Sturdza

et al. 2021

Biology

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The ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related factors such as mobility, vaccination status, and comorbidities and by pathogen-related ones. The pathogenicity of its causative agent, SARS-CoV-2 virus, relates to the functions of the proteins synthesized intracellularly, as guided by viral RNA. These functions are constantly altered through mutations resulting in increased virulence, infectivity, and antibody-evasion abilities. Well-characterized mutations in the spike protein, such as D614G, N439K, Δ69–70, E484K, or N501Y, are currently defining specific variants; however, some less studied mutations outside the spike region, such as p. 3691 in NSP6, p. 9659 in ORF-10, 8782C > T in ORF-1ab, or 28144T > C in ORF-8, have been proposed for altering SARS-CoV-2 virulence and pathogenicity. Therefore, in this study, we focused on A105V mutation of SARS-CoV-2 ORF7a accessory protein, which has been associated with severe COVID-19 clinical manifestation. Molecular dynamics and computational structural analyses revealed that this mutation differentially alters ORF7a dynamics, suggesting a gain-of-function role that may explain its role in the severe form of COVID-19 disease.

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“…The majority of drugs used for SARS-CoV-2 treatment are drugs currently in use for treatment of other diseases [243][244][245], and these have been evaluated for their efficacy using computational drug discovery analysis [246][247][248]. Although NGS has been used primarily for genome identification of SARS-CoV-2 [249][250][251][252], as well as for evaluation of mutations developed during viral spread in different countries [253][254][255], there are some studies wherein RNA sequencing is used for identifying new drug treatments. One such study has used NGS for evaluation of affected genes during SARS-CoV-2 infections.…”

Section: Ngs In Sars-cov-2 Drug Discoverymentioning

confidence: 99%

Microarrays and NGS for Drug Discovery

Pop¹,

Zănoagă²,

Chiroi³

et al. 2021

Drug Design - Novel Advances in the Omics Field and Applications

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Novel technologies and state of the art platforms developed and launched over the last two decades such as microarrays, next-generation sequencing, and droplet PCR have provided the medical field many opportunities to generate and analyze big data from the human genome, particularly of genomes altered by different diseases like cancer, cardiovascular, diabetes and obesity. This knowledge further serves for either new drug discovery or drug repositioning. Designing drugs for specific mutations and genotypes will dramatically modify a patient’s response to treatment. Among other altered mechanisms, drug resistance is of concern, particularly when there is no response to cancer therapy. Once these new platforms for omics data are in place, available information will be used to pursue precision medicine and to establish new therapeutic guidelines. Target identification for new drugs is necessary, and it is of great benefit for critical cases where no alternatives are available. While mutational status is of highest importance as some mutations can be pathogenic, screening of known compounds in different preclinical models offer new and quick strategies to find alternative frameworks for treating more diseases with limited therapeutic options.

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A deletion in SARS‐CoV‐2 ORF7 identified in COVID‐19 outbreak in Uruguay

Cited by 26 publications

References 39 publications

Expansion of a SARS-CoV-2 Delta variant with an 872 nt deletion encompassing ORF7a, ORF7b and ORF8, Poland, July to August 2021

Expansion of a SARS-CoV-2 Delta variant with an 872 nt deletion encompassing ORF7a, ORF7b and ORF8, Poland, July to August 2021

A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19

Microarrays and NGS for Drug Discovery

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