UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Epidemiologically most successful SARS-CoV-2 variant: concurrent mutations in RNA-dependent RNA polymerase and spike protein

Ilmjärv, Sten; Abdul, Fabien; Acosta-Gutiérrez, Silvia; Estarellas, Carolina; Galdadas, Ioannis; Casimir, Marina; Alessandrini, Marco; ... Krause, Karl-Heinz; + view all (2020) Epidemiologically most successful SARS-CoV-2 variant: concurrent mutations in RNA-dependent RNA polymerase and spike protein. MedRxiv: Cold Spring Harbor, NY, USA. Green open access

[thumbnail of Epidemiologically most successful SARS-CoV-2 variant concurrent mutations in RNA-dependent RNA polymerase and spike protein.pdf]
Preview
Text
Epidemiologically most successful SARS-CoV-2 variant concurrent mutations in RNA-dependent RNA polymerase and spike protein.pdf - Other

Download (2MB) | Preview

Abstract

The D614G mutation of the Spike protein is thought to be relevant for SARS-CoV-2 infection. Here we report biological and epidemiological aspects of this mutation. Using pseudotyped lentivectors, we were able to confirm that the G614 variant of the Spike protein is markedly more infectious than the ancestral D614 variant. We demonstrate by molecular modelling that the replacement of aspartate by glycine in position 614 facilitates the transition towards an open state of the Spike protein. To understand whether the increased infectivity of the D614 variant explains its epidemiological success, we analysed the evolution of 27,086 high-quality SARS-CoV-2 genome sequences from GISAID. We observed striking coevolution of D614G with the P323L mutation in the viral polymerase. Importantly, exclusive presence of G614 or L323 did not become epidemiologically relevant. In contrast, the combination of the two mutations gave rise to a viral G/L variant that has all but replaced the initial D/P variant. There was no significant correlation between reported COVID mortality in different countries and the prevalence of the Wuhan versus G/L variant. However, when comparing the speed of emergence and the ultimate predominance in individual countries, the G/L variant displays major epidemiological supremacy. Our results suggest that the P323L mutation, located in the interface domain of the RNA-dependent RNA polymerase (RdRp), is a necessary alteration that led to the epidemiological success of the present variant of SARS-CoV-2.

Type: Working / discussion paper
Title: Epidemiologically most successful SARS-CoV-2 variant: concurrent mutations in RNA-dependent RNA polymerase and spike protein
Open access status: An open access version is available from UCL Discovery
DOI: 10.1101/2020.08.23.20180281
Publisher version: https://doi.org/10.1101/2020.08.23.20180281
Language: English
Additional information: The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
UCL classification: UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10142898
Downloads since deposit
5Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item