Evolutionary changes in the number of dissociable amino acids on spike proteins and nucleoproteins of SARS-CoV-2 variants

Rapoš Božič, Anže (author), Podgornik, Rudolf (author)

The spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for target recognition, cellular entry, and endosomal escape of the virus. At the same time, it is the part of the virus that exhibits the greatest sequence variation across the many variants which have emerged during its evolution. Recent studies have indicated that with progressive lineage emergence, the positive charge on the spike protein has been increasing, with certain positively charged amino acids (AAs) improving the binding of the spike protein to cell receptors. We have performed a detailed analysis of dissociable AAs of more than 1400 different SARS-CoV-2 lineages, which confirms these observations while suggesting that this progression has reached a plateau with Omicron and its subvariants and that the positive charge is not increasing further. Analysis of the nucleocapsid protein shows no similar increase in positive charge with novel variants, which further indicates that positive charge of the spike protein is being evolutionarily selected for. Furthermore, comparison with the spike proteins of known coronaviruses shows that already the wild-type SARS-CoV-2 spike protein carries an unusually large amount of positively charged AAs when compared to most other betacoronaviruses. Our study sheds light on the evolutionary changes in the number of dissociable AAs on the spike protein of SARS-CoV-2, complementing existing studies and providing a stepping stone towards a better understanding of the relationship between the spike protein charge and viral infectivity and transmissibility.

• Language: English
• Keywords: severe acute respiratory syndrome coronavirus 2, spike protein, nucleoprotein, dissociable amino acids, protein charge evolution
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FMF - Faculty of Mathematics and Physics
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 8 str.
• Numbering: Vol. 9, iss. 2, art. vead040
• PID: 20.500.12556/RUL-152409
• UDC: 61
• ISSN on article: 2057-1577
• DOI: 10.1093/ve/vead040
• COBISS.SI-ID: 159560963
• Publication date in RUL: 23.11.2023

Record is a part of a journal

• Title: Virus evolution
• Publisher: Oxford University Press
• ISSN: 2057-1577
• COBISS.SI-ID: 525045785

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0055
• Name: Biofizika polimerov, membran, gelov, koloidov in celic

• Funder: Other - Other funder or multiple funders
• Funding programme: National Natural Science Foundation of China, Key Project
• Project number: 12034019