The evolving proteome of SARS-CoV-2 predominantly uses mutation combination strategy for survival

Patro, L. Ponoop Prasad; Sathyaseelan, Chakkarai; Uttamrao, Patil Pranita; Rathinavelan, Thenmalarchelvi

doi:10.1016/j.csbj.2021.05.054

Cited by 10 publications

(15 citation statements)

References 29 publications

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“… Flowchart depicting the branching of SARS‐CoV‐2 clades/sub‐clades in non‐human hosts phyloproteogram. Comparison of the non‐human hosts SARS‐CoV‐2 clades (nodes 1–19) with the previously defined SARS‐CoV‐2 human clades (grey coloured) (Patro et al, 2021a ) are given at the bottom. Note that the mutations specific to different countries are represented by their flags and the corresponding non‐human hosts are indicated pictorially …”

Section: Resultsmentioning

confidence: 99%

“…By considering the translated proteome sequence of the first published SARS‐CoV‐2 genome sequence (Genbank ID: NC_045512.2) as the reference sequence, the sequences in the local database were subjected to the mutational occurrence analysis. Following the definition used in the previous investigations, high (HR), moderate (MR) and low (LR) recurring mutations (Patro et al, 2021a , Patro et al, 2021b , Uttamrao et al, 2021 ) were calculated based on the percentage frequency (PF) of occurrence in 1016 sequences. A mutation was defined as high, moderate and low recurring respectively if it occurred above 10%, 1%–10% and <1% (but, occurring at least 3 times) percentage frequency.…”

Section: Methodsmentioning

confidence: 99%

“…Pymol software (The PyMOL Molecular Graphics System, Version 2.0, Schrödinger, LLC) was used to project the HR mutations onto the 3D structures of SARS‐CoV‐2 proteins ( Figure S2 ) that were either I‐TASSER generated ( https://zhanggroup.org//COVID‐19/ ) or deposited in PDB. Subsequently, non‐human hosts SARS‐CoV‐2 variant (combination of different amino acids mutations in the proteome (Patro et al, 2021a ) analysis was performed. Further, frequency of different unique variants was also calculated.…”

Section: Methodsmentioning

confidence: 99%

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Geographical distribution of SARS‐CoV‐2 amino acids mutations and the concomitant evolution of seven distinct clades in non‐human hosts

Saras

Patro

Uttamrao

et al. 2022

Zoonoses and Public Health

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Since its first emergence in December 2019, the world has witnessed the eruption of mutations in the SARS‐CoV‐2 genome that have led to increased viral transmissibility and pathogenicity due to sustained local viral transmission. Zooanthroponotic and zoonotic transmissions have further raised concerns as they could result in the emergence of viral variants with a novel antigenicity and transmissibility that could jeopardize the vaccine efficacy. To understand the viral evolution during such transmissions, 1016 whole‐genome sequences (deposited in GISAID as of March 7, 2022) (from 18 countries) corresponding to mink, cat, deer, dog, hyena, tiger, lion, gorilla, Syrian hamster, leopard cat, fishing cat, bear cat, coati, ferret, snow leopard and green monkey have been analysed here. Intriguingly, phyloproteome analysis indicate that Nsp2:R218C, Nsp2:D268‐(deletion), Spike:D614G, Nsp12:P323L, Nsp2:A192V, ORF3a protein:Q57H, N protein:R203K and N protein:G204R/L, Spike:A222V, ORF10 protein:V30L and N protein:A220V are moderate or high recurring and clade decisive mutations, leading to 6 primary clades during the early stage of pandemic. Most interestingly, the human evolved delta variant having a combination of 26 (clade decisive) mutations defines the seventh clade and transmits to non‐human hosts across the globe without exhibiting any country‐specific mutation(s). Nonetheless, Spike:D614G and Nsp12:P323L together with (i)N protein:R203K,N protein:G204R/L,Spike:V70‐, Spike:H69‐, Nsp12:T739I, and Nsp1:M85‐, (ii)Nsp2:A192V, Nsp3:D178Y, (iii)Nsp2:T85I, N protein:P67S and ORF3a protein:Q57H and (iv)Spike:A222V, ORF10 protein:V30L, N protein:A220V and Spike:F486I are specific to Denmark, Netherlands, USA and Latvia respectively and, (v)Nsp2:D268‐ and Nsp13:R292C that are devoid of Spike:D614G and Nsp12:P323L is specific to Netherlands. SARS‐CoV‐2 variants consisting of these mutations are also seen in the human SARS‐CoV‐2 sequences from the same country. Independent country‐specific SARS‐CoV‐2 variant evolution further indicates distinct epidemiological dynamics during zooanthroponotic and zoonotic transmissions. Thus, the results presented here indicate the need for the surveillance of viral evolution in non‐human hosts also during the future pandemic.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Geographical distribution of SARS‐CoV‐2 amino acids mutations and the concomitant evolution of seven distinct clades in non‐human hosts

Saras

Patro

Uttamrao

et al. 2022

Zoonoses and Public Health

Self Cite

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show abstract

“…For this, the gene sequences corresponding to the uORFs were translated using the reference sequences (36) with the help of in-house scripts. The amino acid mutation analyses were done as discussed elsewhere (9,10). The mutations were categorized as highly recurring (HR, occurring with ≥10% percentage frequency), moderately recurring (MR, occurring with 1%-10% percentage frequency), and low recurring (LR, occurring below 1% percentage frequency but should have occurred at least three times) based on their recurrence in the 775,392 viral proteomes.…”

Section: Determination Of Sars-cov-2 Uorf Sequence Conservationmentioning

confidence: 99%

“…Indeed, there are reports (7,8) about the reduced efficacy of the vaccines against the new variants (4). Reports indicate that the number of mutations in the spike protein has increased to 1.4-fold in a time span of 6 months (9,10). This is indicative of challenges in using the existing spike protein antigen-based vaccines (11) when new variants emerge.…”

Section: Introductionmentioning

confidence: 99%

Revelation of Potent Epitopes Present in Unannotated ORF Antigens of SARS-CoV-2 for Epitope-Based Polyvalent Vaccine Design Using Immunoinformatics Approach

et al. 2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kills thousands of people worldwide every day, thus necessitating rapid development of countermeasures. Immunoinformatics analyses carried out here in search of immunodominant regions in recently identified SARS-CoV-2 unannotated open reading frames (uORFs) have identified eight linear B-cell, one conformational B-cell, 10 CD4+ T-cell, and 12 CD8+ T-cell promising epitopes. Among them, ORF9b B-cell and T-cell epitopes are the most promising followed by M.ext and ORF3c epitopes. ORF9b40-48 (CD8+ T-cell epitope) is found to be highly immunogenic and antigenic with the highest allele coverage. Furthermore, it has overlap with four potent CD4+ T-cell epitopes. Structure-based B-cell epitope prediction has identified ORF9b61-68 to be immunodominant, which partially overlaps with one of the linear B-cell epitopes (ORF9b65-69). ORF3c CD4+ T-cell epitopes (ORF3c2-16, ORF3c3-17, and ORF3c4-18) and linear B-cell epitope (ORF3c14-22) have also been identified as the candidate epitopes. Similarly, M.ext and 7a.iORF1 (overlap with M and ORF7a) proteins have promising immunogenic regions. By considering the level of antigen expression, four ORF9b and five M.ext epitopes are finally shortlisted as potent epitopes. Mutation analysis has further revealed that the shortlisted potent uORF epitopes are resistant to recurrent mutations. Additionally, four N-protein (expressed by canonical ORF) epitopes are found to be potent. Thus, SARS-CoV-2 uORF B-cell and T-cell epitopes identified here along with canonical ORF epitopes may aid in the design of a promising epitope-based polyvalent vaccine (when connected through appropriate linkers) against SARS-CoV-2. Such a vaccine can act as a bulwark against SARS-CoV-2, especially in the scenario of emergence of variants with recurring mutations in the spike protein.

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The evolving proteome of SARS-CoV-2 predominantly uses mutation combination strategy for survival

Cited by 10 publications

References 29 publications

Geographical distribution of SARS‐CoV‐2 amino acids mutations and the concomitant evolution of seven distinct clades in non‐human hosts

Geographical distribution of SARS‐CoV‐2 amino acids mutations and the concomitant evolution of seven distinct clades in non‐human hosts

Revelation of Potent Epitopes Present in Unannotated ORF Antigens of SARS-CoV-2 for Epitope-Based Polyvalent Vaccine Design Using Immunoinformatics Approach

SARS-CoV-2 variants with NSP12 P323L/G671S mutations display enhanced virus replication in ferret upper airways and higher transmissibility

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