Bioinformatics study of the A222V substitution in SARS-CoV-2 Spike Protein

Authors

  • Kiky Martha Ariesaka Department of Medicine, Faculty of Medicine, State University of Malang, Malang, Indonesia
  • Moh Mirza Nuryady Biology Education Department, Faculty of Teacher and Training Education, University of Muhammadiyah Malang, Malang, Indonesia , Institute of Parasitology, Department of Biological Science and Pathobiology, Veterinary Medicine University of Vienna, Vienna, Austria
  • Ika Agus Rini Biology Study Program, Institut Teknologi Sumatera, Indonesia , Department of Integrative Biotechnology, Sungkyunkwan University Gyeonggi-do, Suwon, Jangan-gu, Cheoncheon-dong, Seobu-ro 2066, South Korea
Published 2025-12-05
Issue Vol. 16 No. 2 (2025): December 2025
Section Original Research Articles
DOI: https://doi.org/10.30659/sainsmed.v16i2.39242
Keywords: SARS-CoV-2, A222V substitution, Spike protein, Phylogenetic analysis, COVID-19, Mutations

Abstract

COVID-19, caused by the SARS-CoV-2 virus, has resulted in over 200 million infections and 4.3 million global deaths, including more than 3.7 million cases and 110,000 fatalities in Indonesia. SARS-CoV-2, a single-stranded RNA virus, encodes several proteins, including Spike (S), Envelope (E), Membrane (M), and Nucleocapsid (N). The S protein, which consists of S1 and S2 domains, plays a critical role in binding to the ACE2 receptor and facilitating membrane fusion. This study investigates the phylogenetic relationship of the A222V substitution in the S protein relative to various global isolates. We analysed 25 complete SARS-CoV-2 sequences sourced from the GISAID database, conducted multiple sequence alignments using Clustal W in MEGA-X, and constructed phylogenetic trees through the neighbour-joining method. The urgency of this research stems from the need to understand how the A222V mutation affects the virus's infectivity and transmission, which is vital for developing targeted treatments and vaccines. Initially identified in Spain in the summer of 2020, the A222V variant has rapidly spread across Europe, raising concerns about its potential to increase transmissibility or undermine vaccine efficacy. This variant appears to affect protein conformation or stability rather than receptor binding or membrane fusion, underscoring the need to understand these alterations, as they could influence the virus's behaviour and the effectiveness of public health measures. Our findings indicate high mutation rates in the S gene, characterised by diverse point mutations. Phylogenetic analysis demonstrated that A222V isolates are closely clustered with D614G variants. In conclusion, although not all mutations result in amino acid changes, the A222V variant has a limited impact on ACE2 binding but may affect protein stability.

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© 2025 Author(s). Published by Sains Medika: Jurnal Kedokteran dan Kesehatan. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

How to Cite

Ariesaka, K. M., Nuryady, M. M., & Rini, I. A. (2025). Bioinformatics study of the A222V substitution in SARS-CoV-2 Spike Protein. Sains Medika: Jurnal Kedokteran Dan Kesehatan, 16(2), 48-55. https://doi.org/10.30659/sainsmed.v16i2.39242

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