Global landscape of SARS-CoV-2 genomic surveillance and data sharing

Chen, Zhiyuan; Azman, Andrew S.; Chen, Xinhua; Zou, Jiong; Tian, Yuyang; Sun, Ruijia; Xu, Xiangyanyu; Wu, Yani; Lu, Wanying; Ge, Shijia; Zhao, Zeyao; Yang, Juan; Leung, Daniel; Domman, Daryl; Yu, Hongjie

doi:10.1038/s41588-022-01033-y

Cited by 185 publications

(166 citation statements)

References 43 publications

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“…Currently, most neutralizing antibodies or vaccines are developed to target the RBD to block or inhibit viral infection. 80 , 84 – 93 Furthermore, the binding with ACE2 of RBD requires conformational adaptation, and an easier transition from “closed” to “open” conformation of spike protein benefits the viral infection. 32 , 94 – 96 Therefore, mutations in the spike protein of SARS-CoV-2 variants could significantly influence the structure of the spike protein conformation and further the interaction with ACE2 or neutralizing antibodies 32 , 95 , 97 – 100 (Figs.…”

Section: Molecular Characteristics Of Sequence and The Encoded Protei...mentioning

confidence: 99%

Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

Sun

Xie

et al. 2022

Sig Transduct Target Ther

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The persistent COVID-19 pandemic since 2020 has brought an enormous public health burden to the global society and is accompanied by various evolution of the virus genome. The consistently emerging SARS-CoV-2 variants harboring critical mutations impact the molecular characteristics of viral proteins and display heterogeneous behaviors in immune evasion, transmissibility, and the clinical manifestation during infection, which differ each strain and endow them with distinguished features during populational spread. Several SARS-CoV-2 variants, identified as Variants of Concern (VOC) by the World Health Organization, challenged global efforts on COVID-19 control due to the rapid worldwide spread and enhanced immune evasion from current antibodies and vaccines. Moreover, the recent Omicron variant even exacerbated the global anxiety in the continuous pandemic. Its significant evasion from current medical treatment and disease control even highlights the necessity of combinatory investigation of the mutational pattern and influence of the mutations on viral dynamics against populational immunity, which would greatly facilitate drug and vaccine development and benefit the global public health policymaking. Hence in this review, we summarized the molecular characteristics, immune evasion, and impacts of the SARS-CoV-2 variants and focused on the parallel comparison of different variants in mutational profile, transmissibility and tropism alteration, treatment effectiveness, and clinical manifestations, in order to provide a comprehensive landscape for SARS-CoV-2 variant research.

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Section: Molecular Characteristics Of Sequence and The Encoded Protei...mentioning

confidence: 99%

Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

Sun

Xie

et al. 2022

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…With more than 5 million genomes of SARS-CoV-2 sequenced, naturally occurring mutations have been analyzed in a number of strains, including the most recent variants of concern to public health [ 57 , 58 , 59 ]. Overall, SARS-CoV-2 is a relatively conservative virus compared to other RNA viruses [ 60 ].…”

Section: Resultsmentioning

confidence: 99%

Identifying Structural Features of Nucleotide Analogues to Overcome SARS-CoV-2 Exonuclease Activity

Wang

Tao

Morozova

et al. 2022

Viruses

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With the recent global spread of new SARS-CoV-2 variants, there remains an urgent need to develop effective and variant-resistant oral drugs. Recently, we reported in vitro results validating the use of combination drugs targeting both the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and proofreading exonuclease (ExoN) as potential COVID-19 therapeutics. For the nucleotide analogues to be efficient SARS-CoV-2 inhibitors, two properties are required: efficient incorporation by RdRp and substantial resistance to excision by ExoN. Here, we have selected and evaluated nucleotide analogues with a variety of structural features for resistance to ExoN removal when they are attached at the 3′ RNA terminus. We found that dideoxynucleotides and other nucleotides lacking both 2′- and 3′-OH groups were most resistant to ExoN excision, whereas those possessing both 2′- and 3′-OH groups were efficiently removed. We also found that the 3′-OH group in the nucleotide analogues was more critical than the 2′-OH for excision by ExoN. Since the functionally important sequences in Nsp14/10 are highly conserved among all SARS-CoV-2 variants, these identified structural features of nucleotide analogues offer invaluable insights for designing effective RdRp inhibitors that can be simultaneously efficiently incorporated by the RdRp and substantially resist ExoN excision. Such newly developed RdRp terminators would be good candidates to evaluate their ability to inhibit SARS-CoV-2 in cell culture and animal models, perhaps combined with additional exonuclease inhibitors to increase their overall effectiveness.

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“…For each of the three sequences, we created a synthetic sequence with the variable fragments switched to the wildtype match ( Figure 4 , asterisks denote the synthetic variants). These two highly diverged Turkish B.1.1.523 sequences indicate that there are vast uncharted territories in COVID-19 evolution, as we have only sparse sequencing data obtained from central Asian, African, southeast Asian, and east Mediterranean regions where no more than 1.6% of confirmed cases are sequenced [ 34 ]. An evident third case emergent combination of immune response hindering mutations from distinct S protein regions is highlighted by E5 and E6 in Figure 3 a.…”

Section: Resultsmentioning

confidence: 99%

Determining the International Spread of B.1.1.523 SARS-CoV-2 Lineage with a Set of Mutations Highly Associated with Reduced Immune Neutralization

et al. 2022

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Here, we report the emergence of the variant lineage B.1.1.523 that contains a set of mutations including 156_158del, E484K and S494P in the spike protein. E484K and S494P are known to significantly reduce SARS-CoV-2 neutralization by convalescent and vaccinated sera and are considered as mutations of concern. Lineage B.1.1.523 presumably originated in the Russian Federation and spread across European countries with the peak of transmission in April–May 2021. The B.1.1.523 lineage has now been reported from 31 countries. In this article, we analyze the possible origin of this mutation subset and its immune response using in silico methods.

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Global landscape of SARS-CoV-2 genomic surveillance and data sharing

Cited by 185 publications

References 43 publications

Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

Identifying Structural Features of Nucleotide Analogues to Overcome SARS-CoV-2 Exonuclease Activity

Determining the International Spread of B.1.1.523 SARS-CoV-2 Lineage with a Set of Mutations Highly Associated with Reduced Immune Neutralization

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