SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants

Sk Sarif Hassan; Tanishta Bhattacharya; Debaleena Nawn; Ishana Jha; Pallab Basu; Elrashdy M Redwan; Kenneth Lundstrom; Debmalya Barh; Bruno Silva Andrade; Murtaza M Tambuwala; Alaa A Aljabali; Altijana Hromić-Jahjefendić; Wagner Baetas-da-Cruz; Ángel Serrano-Aroca; Vladimir N Uversky

doi:10.1016/j.compbiomed.2023.107899

SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants

Comput Biol Med. 2024 Mar:170:107899. doi: 10.1016/j.compbiomed.2023.107899. Epub 2024 Jan 12.

Authors

Sk Sarif Hassan¹, Tanishta Bhattacharya², Debaleena Nawn³, Ishana Jha⁴, Pallab Basu⁵, Elrashdy M Redwan⁶, Kenneth Lundstrom⁷, Debmalya Barh⁸, Bruno Silva Andrade⁹, Murtaza M Tambuwala¹⁰, Alaa A Aljabali¹¹, Altijana Hromić-Jahjefendić¹², Wagner Baetas-da-Cruz¹³, Ángel Serrano-Aroca¹⁴, Vladimir N Uversky¹⁵

Affiliations

¹ Department of Mathematics, Pingla Thana Mahavidyalaya, Maligram, Paschim Medinipur, 721140, West Bengal, India. Electronic address: [email protected].
² Department of Biological Sciences, Indian Institute of Science Education and Research, Berhampur, IISER Berhampur Transit campus (Govt. ITI Building), Engg. School Junction, Berhampur, 760010, Odisha, India. Electronic address: [email protected].
³ Indian Research Institute for Integrated Medicine (IRIIM), Unsani, Howrah, 711302, West Bengal, India. Electronic address: [email protected].
⁴ Department of Bioinformatics, Pondicherry University, Chinna Kalapet, Kalapet, Puducherry 605014, India. Electronic address: [email protected].
⁵ School of Physics, University of the Witwatersrand, Johannesburg, Braamfontein 2000, 721140, South Africa; Adjunct Faculty, Woxsen School of Sciences, Woxsen University, Telangana, 500 033, India. Electronic address: [email protected].
⁶ Biological Science Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Therapeutic and Protective Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications, New Borg EL-Arab, 21934, Alexandria, Egypt. Electronic address: [email protected].
⁷ PanTherapeutics, Rte de Lavaux 49, CH1095 Lutry, Switzerland. Electronic address: [email protected].
⁸ Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, 721172, India; Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, 31270-901, Brazil. Electronic address: [email protected].
⁹ Laboratory of Bioinformatics and Computational Chemistry, Department of Biological Sciences, State University of Southwest of Bahia (UESB), Jequié 45083-900, Brazil. Electronic address: [email protected].
¹⁰ Lincoln Medical School, University of Lincoln, Brayford Pool Campus, Lincoln LN6 7TS, UK; College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates. Electronic address: [email protected].
¹¹ Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Yarmouk University, Irbid 21163, Jordan. Electronic address: [email protected].
¹² Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnicka cesta 15, 71000 Sarajevo, Bosnia and Herzegovina. Electronic address: [email protected].
¹³ Centre for Experimental Surgery, Translational Laboratory in Molecular Physiology, College of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. Electronic address: [email protected].
¹⁴ Biomaterials and Bioengineering Lab, Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, c/Guillem de Castro 94, 46001 Valencia, Spain. Electronic address: [email protected].
¹⁵ Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA. Electronic address: [email protected].

PMID: 38232455
DOI: 10.1016/j.compbiomed.2023.107899

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rapidly evolving RNA virus behind the COVID-19 pandemic, has spawned numerous variants since its 2019 emergence. The multifunctional Nonstructural protein 14 (NSP14) enzyme, possessing exonuclease and messenger RNA (mRNA) capping capabilities, serves as a key player. Notably, single and co-occurring mutations within NSP14 significantly influence replication fidelity and drive variant diversification. This study comprehensively examines 120 co-mutations, 68 unique mutations, and 160 conserved residues across NSP14 homologs, shedding light on their implications for phylogenetic patterns, pathogenicity, and residue interactions. Quantitative physicochemical analysis categorizes 3953 NSP14 variants into three clusters, revealing genetic diversity. This research underscoresthe dynamic nature of SARS-CoV-2 evolution, primarily governed by NSP14 mutations. Understanding these genetic dynamics provides valuable insights for therapeutic and vaccine development.

Keywords: Clustering; Co-mutations-flow; Invariant residues; Nonstructural protein 14 (NSP14); RdRp; SARS-CoV-2.

MeSH terms

COVID-19* / genetics
Exoribonucleases* / chemistry
Exoribonucleases* / genetics
Exoribonucleases* / metabolism
Humans
Mutation / genetics
Pandemics
Phylogeny
SARS-CoV-2* / genetics
SARS-CoV-2* / metabolism
Viral Nonstructural Proteins* / metabolism
Virus Replication / genetics

Substances

Exoribonucleases
NSP14 protein, SARS-CoV-2
Viral Nonstructural Proteins

Supplementary concepts

SARS-CoV-2 variants