The SARS-CoV-2 ORF10 is not essential in vitro or in vivo in humans

Pancer, Katarzyna; Milewska, Aleksandra; Owczarek, Katarzyna; Dąbrowska, Agnieszka; Kowalski, Michał; Łabaj, Paweł P.; Branicki, Wojciech; Sanak, Marek; Pyrć, Krzysztof

doi:10.1371/journal.ppat.1008959

Cited by 79 publications

(68 citation statements)

References 14 publications

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“…In addition, ORF10 has highly antigenic epitopes ( Table 3 and Table 4 ), which are promising subunit vaccine candidates awaiting further validation studies in vivo. The role of ORF10 is still controversial, as there are two different views: one view relies on the lack of evidence on ORF10 expression or function in host cells, suggesting that ORF10 is a non-essential and most likely non-expressed protein [ 53 ], while the second view suggests ORF10 as a potential target for vaccine development [ 54 ], which supports our prediction.…”

Section: Resultssupporting

confidence: 79%

Identification of Highly Conserved SARS-CoV-2 Antigenic Epitopes with Wide Coverage Using Reverse Vaccinology Approach

Hisham

Ashhab

Hwang

et al. 2021

Viruses

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One of the most effective strategies for eliminating new and emerging infectious diseases is effective immunization. The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) warrants the need for a maximum coverage vaccine. Moreover, mutations that arise within the virus have a significant impact on the vaccination strategy. Here, we built a comprehensive in silico workflow pipeline to identify B-cell- and T-cell-stimulating antigens of SARS-CoV-2 viral proteins. Our in silico reverse vaccinology (RV) approach consisted of two parts: (1) analysis of the selected viral proteins based on annotated cellular location, antigenicity, allele coverage, epitope density, and mutation density and (2) analysis of the various aspects of the epitopes, including antigenicity, allele coverage, IFN-γ induction, toxicity, host homology, and site mutational density. After performing a mutation analysis based on the contemporary mutational amino acid substitutions observed in the viral variants, 13 potential epitopes were selected as subunit vaccine candidates. Despite mutational amino acid substitutions, most epitope sequences were predicted to retain immunogenicity without toxicity and host homology. Our RV approach using an in silico pipeline may potentially reduce the time required for effective vaccine development and can be applicable for vaccine development for other pathogenic diseases as well.

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Section: Resultssupporting

confidence: 79%

Identification of Highly Conserved SARS-CoV-2 Antigenic Epitopes with Wide Coverage Using Reverse Vaccinology Approach

Hisham

Ashhab

Hwang

et al. 2021

Viruses

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“…4 ), these data suggest that the ORF10 protein may only be fleetingly present during infection, if expressed at all. Third, a strain of SARS-CoV-2 in which ORF10 contains a premature stop codon at residue 29 was isolated, and it can still replicate in vivo and in vitro ( 22 ). While most of ORF10, including the N terminus used to bind ZYG11B, is still retained in this strain, this nonetheless implies that the full open reading frame is not required for infection.…”

Section: Discussionmentioning

confidence: 99%

ORF10–Cullin-2–ZYG11B complex is not required for SARS-CoV-2 infection

Mena

Donahue

Vaites

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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In order to understand the transmission and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is necessary to understand the functions of each of the gene products encoded in the viral genome. One feature of the SARS-CoV-2 genome that is not present in related, common coronaviruses is ORF10, a putative 38-amino acid protein-coding gene. Proteomic studies found that ORF10 binds to an E3 ubiquitin ligase containing Cullin-2, Rbx1, Elongin B, Elongin C, and ZYG11B (CRL2ZYG11B). Since CRL2ZYG11B mediates protein degradation, one possible role for ORF10 is to “hijack” CRL2ZYG11B in order to target cellular, antiviral proteins for ubiquitylation and subsequent proteasomal degradation. Here, we investigated whether ORF10 hijacks CRL2ZYG11B or functions in other ways, for example, as an inhibitor or substrate of CRL2ZYG11B. While we confirm the ORF10−ZYG11B interaction and show that the N terminus of ORF10 is critical for it, we find no evidence that ORF10 is functioning to inhibit or hijack CRL2ZYG11B. Furthermore, ZYG11B and its paralog ZER1 are dispensable for SARS-CoV-2 infection in cultured cells. We conclude that the interaction between ORF10 and CRL2ZYG11B is not relevant for SARS-CoV-2 infection in vitro.

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“…A hypothetical 38aa long protein has been described as ORF10. Perhaps this one is the least attractive of the accessory proteins, since it has been shown that it is not essential in human SARS-CoV-2 infection ( 65 ). Its sequence is not similar to other coronavirus, and specific biological functions have not been described yet.…”

Section: Accessory Proteins Of Sars-cov-2mentioning

confidence: 99%

SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns

et al. 2021

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There are still many unanswered questions concerning viral SARS-CoV-2 pathogenesis in COVID-19. Accessory proteins in SARS-CoV-2 consist of eleven viral proteins whose roles during infection are still not completely understood. Here, a review on the current knowledge of SARS-CoV-2 accessory proteins is summarized updating new research that could be critical in understanding SARS-CoV-2 interaction with the host. Some accessory proteins such as ORF3b, ORF6, ORF7a and ORF8 have been shown to be important IFN-I antagonists inducing an impairment in the host immune response. In addition, ORF3a is involved in apoptosis whereas others like ORF9b and ORF9c interact with cellular organelles leading to suppression of the antiviral response in infected cells. However, possible roles of ORF7b and ORF10 are still awaiting to be described. Also, ORF3d has been reassigned. Relevant information on the knowns and the unknowns in these proteins is analyzed, which could be crucial for further understanding of SARS-CoV-2 pathogenesis and to design strategies counteracting their actions evading immune responses in COVID-19.

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The SARS-CoV-2 ORF10 is not essential in vitro or in vivo in humans

Cited by 79 publications

References 14 publications

Identification of Highly Conserved SARS-CoV-2 Antigenic Epitopes with Wide Coverage Using Reverse Vaccinology Approach

Identification of Highly Conserved SARS-CoV-2 Antigenic Epitopes with Wide Coverage Using Reverse Vaccinology Approach

ORF10–Cullin-2–ZYG11B complex is not required for SARS-CoV-2 infection

SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns

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