Translational suppression of SARS-COV-2 ORF8 protein mRNA as a Viable therapeutic target against COVID-19: Computational studies on potential roles of isolated compounds from Clerodendrum volubile leaves

Erukainure, Ochuko L.; Atolanı, Olubunmi; Muhammad, Aliyu; Abarshi, M.M.; Katsayal, Sanusi B.; Chukwuma, Chika I.; Preißner, Robert; Banerjee, Priyanka; Mesaik, M. Ahmed

doi:10.1016/j.compbiomed.2021.104964

Cited by 4 publications

(2 citation statements)

References 70 publications

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“…A recent study suggested that ORF8 mediates immune evasion by downregulating MHC-I molecules like HLA-A2 [22,23] and such finding clearly established the IgG domains similarity of ORF8 to modulate host immune functions and chromatin structure [24]. Dominant mutation of small regulatory protein ORF7a limits viral suppression of the interferon response [25] and we detected one such 62nt deletion abolishing the production of both ORF7a and ORF7b proteins (see, accession no.…”

Section: Resultssupporting

confidence: 75%

SARS-CoV-2 ORF8 gene CAA=TAA and AAA=TAA Termination Codon Mutations found mostly in B.1.1.7 Variants was Independent of Popular L84S Point Mutations

2022

IJCMER

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Five VOCs of SARS-CoV-2 mainly caused million deaths worldwide and named as B.1.1.7 (U.K.), B.1.351 (South Africa), P.1 (Brazil), B.1.617.2 (India), and B.1.1.529 (Africa). In HIV mediated pathogenesis, small trans activator proteins (TAT, NEF, REV) modulate transcription of cellular genes. Similarly, preliminary reports indicated that corona virus ORF8 protein acts as histone mimics disrupting chromatic structure with many epigenetic changes and immune modulator functions. ORF8 protein had also some similarities to immunoglobulin domains and inhibited HMC-1 and IFN-beta functions. During evolution a 382-nucleotide deletion (∆382) in the ORF8 region of the corona virus genome leads to weak virus load and weak pathogenicity (accession no.MT374101). We BLAST searched deletion boundary and was selected few ORF8 protein truncated mutants. The C>T base change at 27972nt and another A>T base change at 28095nt created two termination codons (CAA=TAA and AAA=TAA) to produce 26AA and 67AA long ORF8 truncated proteins. Similar Blast-N search with oligonucleotides selected at the mutation boundaries gave many ORF8 mutants with distinct S24L, V32L, P38S, R52I, A65V, Y73C, L84S, K92E and V100L mutations with or without TAA termination mutations. Major mutations found in B.1.1.7 lineage which had spike 69HV and 145Y mutations and ORF1ab polyprotein 3675KSF deletion. However, one ORF8 mutant (accession no. OW221449) belongs to Omicron BA.2 variant with 24LPP spike deletion and others to Omicron BA.5 variants (accession nos. OP733645 and OP671680) with 24LPP and 69HV deletion in the spike protein. One termination codon mutant (accession no. OP711842) has also 63nt ORF7a/b deletions. Mutation did not change the hairpin structure in the ORF8 gene and ORF8 protein formed dimeric stable globular 3-D structure to interact with many host proteins. Clearly, generation of such abundant B.1.1.7 lineage ORF8 protein truncated mutants may be one of the causes for the extinction of Alpha variant of corona virus in 2021. Roles of ORF8 mutants as host proteins modulator were explained in light of other deletions and mutations in corona virus genome.

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Section: Resultssupporting

confidence: 75%

SARS-CoV-2 ORF8 gene CAA=TAA and AAA=TAA Termination Codon Mutations found mostly in B.1.1.7 Variants was Independent of Popular L84S Point Mutations

2022

IJCMER

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show abstract

Section: Resultssupporting

confidence: 75%

Untitled

2022

IJCMER

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In HIV mediated pathogenesis, small trans activator proteins (TAT, NEF, REV) modulate transcription of cellular genes. Similarly, preliminary reports indicated that corona virus ORF8 protein acts as histone mimics disrupting chromatic structure with many epigenetic changes and immune modulator functions. ORF8 protein had also some similarities to immunoglobulin domains and inhibited HMC-1 and IFN-beta functions.During evolution a 382-nucleotide deletion (∆382) in the ORF8 region of the corona virus genome leads to weak virus load and weak pathogenicity (accession no.MT374101). We BLAST searched deletion boundary and was selected few ORF8 protein truncated mutants. The C>T base change at 27972nt and another A>T base change at 28095nt created two termination codons (CAA=TAA and AAA=TAA) to produce 26AA and 67AA long ORF8 truncated proteins. Similar Blast-N search with oligonucleotides selected at the mutation boundaries gave many ORF8 mutants with distinct S24L, V32L, P38S, R52I, A65V, Y73C, L84S, K92E and V100L mutations with or without TAA termination mutations.Major mutations found in B.1.1.7 lineage which had spike 69HV and 145Y mutations and ORF1ab polyprotein 3675KSF deletion. However, one ORF8 mutant (accession no. OW221449) belongs to Omicron BA.2 variant with 24LPP spike deletion and others to Omicron BA.5 variants (accession nos. OP733645 and OP671680) with 24LPP and 69HV deletion in the spike protein. One termination codon mutant (accession no. OP711842) has also 63nt ORF7a/b deletions. Mutation did not change the hairpin structure in the ORF8 gene and ORF8 protein formed dimeric stable globular 3-D structure to interact with many host proteins. Clearly, generation of such abundant B.1.1.7 lineage ORF8 protein truncated mutants may be one of the causes for the extinction of Alpha variant of corona virus in 2021. Roles of ORF8 mutants as host proteins modulator were explained in light of other deletions and mutations in corona virus genome.

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Predicting Compound-Protein Interaction by Deepening the Systemic Background via Molecular Network Feature Embedding

Wang

Zhu

et al. 2022

2022 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)

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Translational suppression of SARS-COV-2 ORF8 protein mRNA as a Viable therapeutic target against COVID-19: Computational studies on potential roles of isolated compounds from Clerodendrum volubile leaves

Cited by 4 publications

References 70 publications

SARS-CoV-2 ORF8 gene CAA=TAA and AAA=TAA Termination Codon Mutations found mostly in B.1.1.7 Variants was Independent of Popular L84S Point Mutations

SARS-CoV-2 ORF8 gene CAA=TAA and AAA=TAA Termination Codon Mutations found mostly in B.1.1.7 Variants was Independent of Popular L84S Point Mutations

Untitled

Predicting Compound-Protein Interaction by Deepening the Systemic Background via Molecular Network Feature Embedding

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