Evolutionary history of the SARS-CoV-2 Gamma variant of concern (P.1): a perfect storm

Yépez, Yuri; Marcano-Ruiz, Mariana; Bezerra, Rafael Santos; Fam, Bibiana Sampaio de Oliveira; Ximenez, João Pb; Silva, Wilson A.; Bortolini, María Cátira

doi:10.1590/1678-4685-gmb-2021-0309

Cited by 9 publications

(4 citation statements)

References 115 publications

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“…This mutation plays a role in enhancing binding with ACE2 [29,30]. The Gamma variant contains mutations, such as N501Y, E484K, and K417T in the RBD [31]. Compar-ing the Alpha variant with Gamma, we found two more pockets for the Gamma variant, which could be attributed to the different number of mutations between the two variants.…”

Section: Discussionmentioning

confidence: 84%

Different In Silico Approaches Using Heterocyclic Derivatives against the Binding between Different Lineages of SARS-CoV-2 and ACE2

et al. 2023

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Over the last few years, the study of the SARS-CoV-2 spike protein and its mutations has become essential in understanding how it interacts with human host receptors. Since the crystallized structure of the spike protein bound to the angiotensin-converting enzyme 2 (ACE2) receptor was released (PDB code 6M0J), in silico studies have been performed to understand the interactions between these two proteins. Specifically, in this study, heterocyclic compounds with different chemical characteristics were examined to highlight the possibility of interaction with the spike protein and the disruption of the interaction between ACE2 and the spike protein. Our results showed that these compounds interacted with the spike protein and interposed in the interaction zone with ACE2. Although further studies are needed, this work points to these heterocyclic push–pull compounds as possible agents capable of interacting with the spike protein, with the potential for the inhibition of spike protein–ACE2 binding.

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Section: Discussionmentioning

confidence: 84%

Different In Silico Approaches Using Heterocyclic Derivatives against the Binding between Different Lineages of SARS-CoV-2 and ACE2

et al. 2023

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“…Future therapies can target these regions of positive selection since they affect the fitness of the SARS-CoV-2 virus [44]. Previous studies have similarly observed positive selection in the SARS-CoV-2 spike protein open reading frame [44,45] and ORF1a [46,47]. SARS-CoV-2 ORF1a and ORF1b genomic RNAs are translated and cleaved into 16 NSPs [48] associated with viral genomic replication as well as suppression of host immune response and gene expression [49].…”

Section: Discussionmentioning

confidence: 96%

Mutational Patterns Observed in SARS-CoV-2 Genomes Sampled From Successive Epochs Delimited by Major Public Health Events in Ontario, Canada: Genomic Surveillance Study

Chen¹,

Randhawa²,

Soltysiak³

et al. 2022

JMIR Bioinform Biotech

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Background The emergence of SARS-CoV-2 variants with mutations associated with increased transmissibility and virulence is a public health concern in Ontario, Canada. Characterizing how the mutational patterns of the SARS-CoV-2 genome have changed over time can shed light on the driving factors, including selection for increased fitness and host immune response, that may contribute to the emergence of novel variants. Moreover, the study of SARS-CoV-2 in the microcosm of Ontario, Canada can reveal how different province-specific public health policies over time may be associated with observed mutational patterns as a model system. Objective This study aimed to perform a comprehensive analysis of single base substitution (SBS) types, counts, and genomic locations observed in SARS-CoV-2 genomic sequences sampled in Ontario, Canada. Comparisons of mutational patterns were conducted between sequences sampled during 4 different epochs delimited by major public health events to track the evolution of the SARS-CoV-2 mutational landscape over 2 years. Methods In total, 24,244 SARS-CoV-2 genomic sequences and associated metadata sampled in Ontario, Canada from January 1, 2020, to December 31, 2021, were retrieved from the Global Initiative on Sharing All Influenza Data database. Sequences were assigned to 4 epochs delimited by major public health events based on the sampling date. SBSs from each SARS-CoV-2 sequence were identified relative to the MN996528.1 reference genome. Catalogues of SBS types and counts were generated to estimate the impact of selection in each open reading frame, and identify mutation clusters. The estimation of mutational fitness over time was performed using the Augur pipeline. Results The biases in SBS types and proportions observed support previous reports of host antiviral defense activity involving the SARS-CoV-2 genome. There was an increase in U>C substitutions associated with adenosine deaminase acting on RNA (ADAR) activity uniquely observed during Epoch 4. The burden of novel SBSs observed in SARS-CoV-2 genomic sequences was the greatest in Epoch 2 (median 5), followed by Epoch 3 (median 4). Clusters of SBSs were observed in the spike protein open reading frame, ORF1a, and ORF3a. The high proportion of nonsynonymous SBSs and increasing dN/dS metric (ratio of nonsynonymous to synonymous mutations in a given open reading frame) to above 1 in Epoch 4 indicate positive selection of the spike protein open reading frame. Conclusions Quantitative analysis of the mutational patterns of the SARS-CoV-2 genome in the microcosm of Ontario, Canada within early consecutive epochs of the pandemic tracked the mutational dynamics in the context of public health events that instigate significant shifts in selection and mutagenesis. Continued genomic surveillance of emergent variants will be useful for the design of public health policies in response to the evolving COVID-19 pandemic.

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“…Compared with the sequence of the Beta mutant, in the S protein RBD of the Gamma mutant, lysine at position 417 is replaced with threonine (K417T), while the E484K and N501Y mutations are retained. In addition, there is an L18F mutation in the NTD, and threonine at position 20 is replaced by asparagine (T20N), proline at position 26 is replaced by serine (P26S), etc., ( Raman et al, 2021 ; Yépez et al, 2022 ). Therefore, for the ACE2 receptor, the Gamma variant has a binding affinity similar to that of the Beta variant, and mutation at these sites significantly reduces the neutralizing efficacy of monoclonal antibodies against the RBD and NTD.…”

Section: Sars-cov-2 Is Mutatingmentioning

confidence: 99%

Novel receptor, mutation, vaccine, and establishment of coping mode for SARS-CoV-2: current status and future

et al. 2023

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Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant pneumonia in December 2019, the cumulative number of infected people worldwide has exceeded 670 million, with over 6.8 million deaths. Despite the marketing of multiple series of vaccines and the implementation of strict prevention and control measures in many countries, the spread and prevalence of SARS-CoV-2 have not been completely and effectively controlled. The latest research shows that in addition to angiotensin converting enzyme II (ACE2), dozens of protein molecules, including AXL, can act as host receptors for SARS-CoV-2 infecting human cells, and virus mutation and immune evasion never seem to stop. To sum up, this review summarizes and organizes the latest relevant literature, comprehensively reviews the genome characteristics of SARS-CoV-2 as well as receptor-based pathogenesis (including ACE2 and other new receptors), mutation and immune evasion, vaccine development and other aspects, and proposes a series of prevention and treatment opinions. It is expected to provide a theoretical basis for an in-depth understanding of the pathogenic mechanism of SARS-CoV-2 along with a research basis and new ideas for the diagnosis and classification, of COVID-19-related disease and for drug and vaccine research and development.

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Evolutionary history of the SARS-CoV-2 Gamma variant of concern (P.1): a perfect storm

Cited by 9 publications

References 115 publications

Different In Silico Approaches Using Heterocyclic Derivatives against the Binding between Different Lineages of SARS-CoV-2 and ACE2

Different In Silico Approaches Using Heterocyclic Derivatives against the Binding between Different Lineages of SARS-CoV-2 and ACE2

Mutational Patterns Observed in SARS-CoV-2 Genomes Sampled From Successive Epochs Delimited by Major Public Health Events in Ontario, Canada: Genomic Surveillance Study

Novel receptor, mutation, vaccine, and establishment of coping mode for SARS-CoV-2: current status and future

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