Unveiling diffusion pattern and structural impact of the most invasive SARS-CoV-2 spike mutation

  1. Emiliano Trucchi
  2. Paolo Gratton
  3. Fabrizio Mafessoni
  4. Stefano Motta
  5. Francesco Cicconardi
  6. Giorgio Bertorelle
  7. Ilda D’Annessa
  8. Daniele Di Marino

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Abstract

Starting in Wuhan, China, SARS-CoV-2 epidemics quickly propagated worldwide in less than three months, geographically sorting genomic variants in newly established propagules of infections. Stochasticity in transmission within and between countries and/or actual advantage in virus transmissibility could explain the high frequency reached by some genomic variants during the course of the outbreak.

Using a suite of statistical, population genetics, and theoretical approaches, we show that the globally most represented spike protein variant ( i.e. , the G clade, A → G nucleotide change at genomic position 23,403; D → G amino acid change at spike protein position 614) i) underwent a significant demographic expansion in most countries not explained by stochastic effects or enhanced pathogenicity; ii) affects the spike S1/S2 furin-like site increasing its conformational plasticity (short range effect), and iii) modifies the internal motion of the receptor-binding domain affecting its cross-connection with other functional domains (long-range effect).

Our study unambiguously links the spread of the G614 with a non-random process, and we hypothesize that this process is related to the selective advantage produced by a specific structural modification of the spike protein. We conclude that the different conformation of the S1/S2 proteolytic site is at the basis of the higher transmission rate of this invasive SARS-CoV-2 variant, and provide structural information to guide the design of selective and efficient drugs.

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    SciScore for 10.1101/2020.05.14.095620: (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
    Alignment was checked by eye in Aliview (Larsson 2014) to remove indels, and then parsed using a custom python script to trim sequences before position 150 and after position 29150, and discard sequences with more than 500 missing bases.
    python
    suggested: (IPython, RRID:SCR_001658)
    The demographic history of the D/G614 SARS-CoV-2 variants in each territory was reconstructed using the Bayesian Skyline plot analyses as implemented in Beast v2.6 (Bouckaert et al 2019).
    Beast
    suggested: (BEAST, RRID:SCR_010228)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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  2. Version published to 10.1101/2020.05.14.095620 on bioRxiv