The SARS-CoV-2 infection in Thailand: analysis of spike variants complemented by protein structure insights

  1. Sirawit Ittisoponpisan
  2. Shalip Yahangkiakan
  3. Michael J E Sternberg
  4. Alessia David

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Abstract

Thailand was the first country outside China to officially report COVID-19 cases. Despite the strict regulations for international arrivals, up until February 2021, Thailand had been hit by two major outbreaks. With a large number of SARS-CoV-2 sequences collected from patients, the effects of many genetic variations, especially those unique to Thai strains, are yet to be elucidated. In this study, we analysed 439,197 sequences of the SARS-CoV-2 spike protein collected from NCBI and GISAID databases. 595 sequences were from Thailand and contained 52 variants, of which 6 had not been observed outside Thailand (p.T51N, p.P57T, p.I68R, p.S205T, p.K278T, p.G832C). These variants were not predicted to be of concern. We demonstrate that the p.D614G, although already present during the first Thai outbreak, became the prevalent strain during the second outbreak, similarly to what was described in other countries. Moreover, we show that the most common variants detected in Thailand (p.A829T, p.S459F and p.S939F) do not appear to cause any major structural change to the spike trimer or the spike-ACE2 interaction. Among the variants identified in Thailand was p.N501T. This variant, which involves an asparagine critical for spike-ACE2 binding, was not predicted to increase SARS-CoV-2 binding, thus in contrast to the variant of global concern p.N501Y. In conclusion, novel variants identified in Thailand are unlikely to increase the fitness of SARS-CoV-2. The insights obtained from this study could aid SARS-CoV-2 variants prioritisations and help molecular biologists and virologists working on strain surveillance.

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    SciScore for 10.1101/2022.01.01.474713: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The final dataset consisted of 53,050 sequences from NCBI and 386,147 from GISAID (439,197
    NCBI
    suggested: (NCBI, RRID:SCR_006472)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    One limitation in this study is that the Thai sequences available on NCBI and GISAID were from two sources: the state quarantines and domestic hospitals/research institutions. The strains collected in the state quarantine zones are likely imported in Thailand and less likely to cause local transmission. Unfortunately, the available data did not allow to distinguish the variant source. Hence, the number of variants found in Thailand in this study could be an overestimation of the variants that actually caused local transmissions. Nevertheless, it is always important to keep tracking of possible new strains as the mutation rate is very high in single-stranded RNA viruses compared to DNA viruses [44]. The high mutation rate poses a great challenge for developing vaccines [45], highlighting why incorporating conserved residue information into structural analyses could be essential for discovering other alternative measures for COVID-19 diagnosis, treatment, and prevention. Another limitation is that at the time of this study only the 3D coordinates of the spike trimer and the spike-hACE2 interaction were available. Recently, the spike protein was reported to bind to other human proteins, such as CD209 [46], HAVCR1 [47], and NRP1 [48, 49], and other mammal proteins [50]. Therefore, in this study, the number of interface residues could have been underestimated, and it is possible that in the future, additional variants will be classified according to their effect on additional viru...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2022.01.01.474713v1 on bioRxiv