Outbreak.info genomic reports: scalable and dynamic surveillance of SARS-CoV-2 variants and mutations

Gangavarapu, Karthik; Latif, Alaa Abdel; Mullen, Julia; Alkuzweny, Manar; Hufbauer, Emory; Tsueng, Ginger; Haag, Emily; Zeller, Mark; Aceves, Christine M.; Zaiets, Karina; Cano, Marco Alvarado; Zhou, Jerry; Qian, Zhongchao; Sattler, Rachel A.; Matteson, Nathaniel L.; Levy, Joshua I.; Lee, Raphael Tc; Freitas, Lucas; Maurer‐Stroh, Sebastian; Suchard, Marc A.; Wu, Chunlei; Su, Andrew I.; Andersen, Kristian G.; Hughes, Laura D.

doi:10.1101/2022.01.27.22269965

Cited by 96 publications

(116 citation statements)

References 59 publications

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“…To assess the suitability of different SNP targets for lineage specification in the ASP-PCR platform, global sequencing data published as part of the GISAID repository were utilized, leveraging the collation performed by https://www.Outbreak.info ( 16 , 23 ). The country-specific positive percent agreement (PPA), negative percent agreement (NPA), positive predictive value (PPV), and negative predictive value (NPV) for various lineage-defining SNPs were calculated ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Highly Sensitive Lineage Discrimination of SARS-CoV-2 Variants through Allele-Specific Probe PCR

et al. 2022

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Tools to detect SARS-CoV-2 variants of concern and track the ongoing evolution of the virus are necessary to support public health efforts and the design and evaluation of novel COVID-19 therapeutics and vaccines. Although next-generation sequencing (NGS) has been adopted as the gold standard method for discriminating SARS-CoV-2 lineages, alternative methods may be required when processing samples with low viral loads or low RNA quality.

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Section: Resultsmentioning

confidence: 99%

Highly Sensitive Lineage Discrimination of SARS-CoV-2 Variants through Allele-Specific Probe PCR

et al. 2022

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“…Finally, we observe three high-frequency combinations of mutations, including the S:E484K mutation of concern as well as other mutations of interest according to outbreak.info [ 19 ] (notably S:Δ140–142, S:Δ136–144 and nsp6:Δ106–108, also referred to as ORF1a:Δ3675–3677; columns 7, 8 and 10 in Fig 4 ). These combinations have later been designated as Pango lineages B.1.1.524, AT.1 and B.1.1.525 (for columns 7, 8 and 10 in Fig 4 , respectively).…”

Section: Resultsmentioning

confidence: 99%

“…This loop is a part of the NTD antigenic supersite ( Fig 10 ; [ 42 ]), and nearby residues, including S:152, were recently shown to bind highly neutralizing 4A8 antibody from a convalescent patient [ 43 ]. Besides Russia, S:M153T was prevalent in several other countries including Kazakhstan and Mongolia ( S2 Table ) [ 19 ] which has a long border with Russia, suggesting common ancestry of this change in these countries.…”

Section: Resultsmentioning

confidence: 99%

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Spread of endemic SARS-CoV-2 lineages in Russia before April 2021

et al. 2022

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In 2021, the COVID-19 pandemic was characterized by global spread of several lineages with evidence for increased transmissibility. Throughout the pandemic, Russia has remained among the countries with the highest number of confirmed COVID-19 cases, making it a potential hotspot for emergence of novel variants. Here, we show that among the globally significant variants of concern that have spread globally by late 2020, alpha (B.1.1.7), beta (B.1.351) or gamma (P.1), none have been sampled in Russia before the end of 2020. Instead, between summer 2020 and spring 2021, the epidemic in Russia has been characterized by the spread of two lineages that were rare in most other countries: B.1.1.317 and a sublineage of B.1.1 including B.1.1.397 (hereafter, B.1.1.397+). Their frequency has increased concordantly in different parts of Russia. On top of these lineages, in late December 2020, alpha (B.1.1.7) emerged in Russia, reaching a frequency of 17.4% (95% C.I.: 12.0%-24.4%) in March 2021. Additionally, we identify three novel distinct lineages, AT.1, B.1.1.524 and B.1.1.525, that have started to spread, together reaching the frequency of 11.8% (95% C.I.: 7.5%-18.1%) in March 2021. These lineages carry combinations of several notable mutations, including the S:E484K mutation of concern, deletions at a recurrent deletion region of the spike glycoprotein (S:Δ140–142, S:Δ144 or S:Δ136–144), and nsp6:Δ106–108 (also known as ORF1a:Δ3675–3677). Community-based PCR testing indicates that these variants have continued to spread in April 2021, with the frequency of B.1.1.7 reaching 21.7% (95% C.I.: 12.3%-35.6%), and the joint frequency of B.1.1.524 and B.1.1.525, 15.2% (95% C.I.: 7.6%-28.2%). Although these variants have been displaced by the onset of delta variant in May-June 2021, lineages B.1.1.317, B.1.1.397+, AT.1, B.1.1.524 and B.1.1.525 and the combinations of mutations comprising them that are found in other lineages merit monitoring.

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“…During the submission of this work, Omicron's sister strains, BA.2 (B.1.1.529.2), BA.3 (B.1.1.529.3), BA.4 (B.1.1.529.4) and BA.5 (B.1.1.529.5) were identified and were shown to have higher transmissibility [47][48][49][50] . Interestingly, the mutations found in the β-core region of BA.1 remain in the other four Omicron strains.…”

mentioning

confidence: 99%

S373P Mutation Stabilizes the Receptor-binding Domain of Spike Protein in Omicron and Promotes Binding

Zheng

Xiao

Tong

et al. 2022

Preprint

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Recently, a cluster of several newly occurring mutations on Omicron, which is currently the dominant SARS-CoV-2 variant, are found at the (mechanically) stable β-core region of spike protein's receptor-binding domain (RBD), where mutation rarely happened before. Notably, the binding of SARS-CoV-2 to human receptor ACE2 via RBD happens in a dynamic airway environment, where mechanical force caused by coughing or sneezing occurs and applies to the proteins. Thus, we used atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) to measure the stability of RBDs and found that the unfolding force of Omicron RBD increased by 20% compared with the wild-type. Molecular dynamics simulations revealed that Omicron RBD showed more hydrogen bonds in the β-core region due to the closing of the α-helical motif caused primarily by the S373P mutation, which was further confirmed by the experiment. This work reveals the stabilizing effect of the S373P mutation and suggests mechanical stability becomes another important factor in SARS-CoV-2 mutation selection.

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Outbreak.info genomic reports: scalable and dynamic surveillance of SARS-CoV-2 variants and mutations

Cited by 96 publications

References 59 publications

Highly Sensitive Lineage Discrimination of SARS-CoV-2 Variants through Allele-Specific Probe PCR

Highly Sensitive Lineage Discrimination of SARS-CoV-2 Variants through Allele-Specific Probe PCR

Spread of endemic SARS-CoV-2 lineages in Russia before April 2021

S373P Mutation Stabilizes the Receptor-binding Domain of Spike Protein in Omicron and Promotes Binding

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