Comprehensive annotations of the mutational spectra of SARS‐CoV‐2 spike protein: a fast and accurate pipeline

Rahman, M. Shaminur; Islam, M. Rafiul; Hoque, M. Nazmul; Alam, A. S. M. Rubayet Ul; Akther, Masuda; Puspo, J. Akter; Akter, Salma; Anwar, Azraf; Sultana, Munawar; Hossain, M. Anwar

doi:10.1111/tbed.13834

Cited by 38 publications

(46 citation statements)

References 58 publications

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Section: Methodsmentioning

confidence: 99%

“…Frequencies of SARS-CoV-2 Spike protein variants were previously reported [24,25]. Dataset S1 of Supplementary material [24] contains more than 32.000 sequences of SARS-CoV-2 Spike; Dataset S2 of Supplementary material [25] contains the relative frequency of each SARS-CoV-2 Spike missense. Dataset S3 of Supplementary material includes 29 sequences of SARS-CoV previously reported [26,27]The functional domains of protein were mapped by CD-search [43] while the trans-membrane and inner domains were predicted by TMHMM Server v. 2.0.…”

Section: Methodsmentioning

confidence: 99%

“…On June 2020 the frequencies of the individual amino acid substitutions (N501Y, A570D, D614G, P681H, T716I, S982A, D1118Y) in COVD-19 clinical samples were quite low except the frequency of the D614G that was already high suggesting that the punctual mutation D614G represented already a selective advantage for the virus [24,25] (Table 1). Figure 1C illustrates the relative distribution of annotated SARS-CoV-2 Spike mutations with respect to each protein domain as inferred from [24] (Dataset S1), and [25] (Dataset S2), and also shows the results of this analysis with SARS-CoV Spike mutations [26,27] (Dataset S3). Spike protein variants encompassing 7 domains (N-terminal, receptor-binding domain (RBD), fusion peptide, HR1, HR2, trans-membrane domain and inner domain), and 3 inter-domain regions (RBD-fusion peptide, fusion peptide-HR1 and HR1-HR2) were analyzed.…”

Section: The Emerging Variant Of Sars-cov-2 Spike With Multiple Aminomentioning

confidence: 99%

“…The data show distinct patterns in the different geographical regions. Specifically, in Eastern Asia the D614G variant was described in January 2020 at low frequency (3.8%) and then it was subject to a decremental trend over time ( The database was constructed from the data in Rhaman et al, 2020 [24].…”

Section: The Emerging Variant Of Sars-cov-2 Spike With Multiple Aminomentioning

confidence: 99%

“…Frequencies of SARS-CoV-2 Spike protein variants were previously reported [24,25]. Dataset S1 of [26,27]The functional domains of protein were mapped by CD-search [43] while the trans- Bat coronavirus (taxid:1508220).…”

Section: Dataset Analysismentioning

confidence: 99%

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The lethal triad: SARS-CoV-2 Spike, ACE2 and TMPRSS2. Mutations in host and pathogen may affect the course of pandemic

Calcagnile

Forgez

Alifano

et al. 2021

Preprint

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Variants of SARS-CoV-2 have been identified rapidly after the beginning of pandemic. One of them, involving the spike protein and called D614G, represents a substantial percentage of currently isolated strains. While research on this variant was ongoing worldwide, on December 20th 2020 the European Centre for Disease Prevention and Control reported a Threat Assessment Brief describing the emergence of a new variant of SARS-CoV-2, named B.1.1.7, harboring multiple mutations mostly affecting the Spike protein. This viral variant has been recently associated with a rapid increase in COVID-19 cases in South East England, with alarming implications for future virus transmission rates. Specifically, of the nine amino acid replacements that characterize the Spike in the emerging variant, four are found in the region between the Fusion Peptide and the RBD domain (namely the already known D614G, together with A570D, P681H, T716I), and one, N501Y, is found in the Spike Receptor Binding Domain – Receptor Binding Motif (RBD-RBM). In this study, by using in silico biology, we provide evidence that these amino acid replacements have dramatic effects on the interactions between SARS-CoV-2 Spike and the host ACE2 receptor or TMPRSS2, the protease that induces the fusogenic activity of Spike. Mostly, we show that these effects are strongly dependent on ACE2 and TMPRSS2 polymorphism, suggesting that dynamics of pandemics are strongly influenced not only by virus variation but also by host genetic background.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: The Emerging Variant Of Sars-cov-2 Spike With Multiple Aminomentioning

confidence: 99%

Section: The Emerging Variant Of Sars-cov-2 Spike With Multiple Aminomentioning

confidence: 99%

Section: Dataset Analysismentioning

confidence: 99%

See 3 more Smart Citations

The lethal triad: SARS-CoV-2 Spike, ACE2 and TMPRSS2. Mutations in host and pathogen may affect the course of pandemic

Calcagnile

Forgez

Alifano

et al. 2021

Preprint

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Evolutionary dynamics of SARS‐CoV‐2 nucleocapsid protein and its consequences

Rahman

Islam

Alam³

et al. 2020

Journal of Medical Virology

114

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The emerged novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has created a global health crisis that warrants an accurate and detailed characterization of the rapidly evolving viral genome for understanding its epidemiology, pathogenesis, and containment. Here, we explored 61,485 sequences of the nucleocapsid (N) protein, a potent diagnostic and prophylactic target, for identifying the mutations to review their roles in real‐time polymerase chain reaction based diagnosis and observe consequent impacts. Compared to the Wuhan reference strain, a total of 1034 unique nucleotide mutations were identified in the mutant strains (49.15%, n = 30,221) globally. Of these mutations, 367 occupy primer binding sites including the 3′‐end mismatch to the primer‐pair of 11 well‐characterized primer sets. Noteworthily, CDC (USA) recommended the N2 primer set contained a lower mismatch than the other primer sets. Moreover, 684 amino acid (aa) substitutions were located across 317 (75.66% of total aa) unique positions including 82, 21, and 83 of those in the RNA binding N‐terminal domain (NTD), SR‐rich region, and C‐terminal dimerization domain, respectively. Moreover, 11 in‐frame deletions, mostly (n = 10) within the highly flexible linker region, were revealed, and the rest was within the NTD region. Furthermore, we predicted the possible consequence of high‐frequency mutations (≥20) and deletions on the tertiary structure of the N protein. Remarkably, we observed that a high frequency (67.94% of mutated sequences) co‐occuring mutations (R203K and G204R) destabilized and decreased overall structural flexibility. The N protein of SARS‐CoV‐2 comprises an average of 1.2 mutations per strain compared to 4.4 and 0.4 in Middle East respiratory syndrome‐related coronavirus and SARS‐CoV, respectively. Despite being proposed as the alternative target to spike protein for vaccine and therapeutics, the ongoing evolution of the N protein may challenge these endeavors, thus needing further immunoinformatics analyses. Therefore, continuous monitoring is required for tracing the ongoing evolution of the SARS‐CoV‐2 N protein in prophylactic and diagnostic interventions.

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A rapid and cost‐effective multiplex ARMS‐PCR method for the simultaneous genotyping of the circulating SARS‐CoV‐2 phylogenetic clades

Islam¹,

Alam²,

Sakib³

et al. 2021

Journal of Medical Virology

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Tracing the globally circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) phylogenetic clades by high-throughput sequencing is costly, timeconsuming, and labor-intensive. We here propose a rapid, simple, and cost-effective amplification refractory mutation system (ARMS)-based multiplex reverse-transcription polymerase chain reaction (PCR) assay to identify six distinct phylogenetic clades: S, L, V, G, GH, and GR. Our multiplex PCR is designed in a mutually exclusive way to identify V-S and G-GH-GR clade variants separately. The pentaplex assay included all five variants and the quadruplex comprised of the triplex variants alongside either V or S clade mutations that created two separate subsets. The procedure was optimized with 0.2-0.6 µM primer concentration, 56-60°C annealing temperature, and 3-5 ng/µl complementary DNA to validate on 24 COVID-19-positive samples. Targeted Sanger sequencing further confirmed the presence of the clade-featured mutations with another set of primers. This multiplex ARMS-PCR assay is a fast, low-cost alternative and convenient to discriminate the circulating phylogenetic clades of SARS-CoV-2.

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Comprehensive annotations of the mutational spectra of SARS‐CoV‐2 spike protein: a fast and accurate pipeline

Cited by 38 publications

References 58 publications

The lethal triad: SARS-CoV-2 Spike, ACE2 and TMPRSS2. Mutations in host and pathogen may affect the course of pandemic

The lethal triad: SARS-CoV-2 Spike, ACE2 and TMPRSS2. Mutations in host and pathogen may affect the course of pandemic

Evolutionary dynamics of SARS‐CoV‐2 nucleocapsid protein and its consequences

A rapid and cost‐effective multiplex ARMS‐PCR method for the simultaneous genotyping of the circulating SARS‐CoV‐2 phylogenetic clades

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