THERMAL SCIENCE

International Scientific Journal

Marko E Popović

,

Vojin M Tadić

,

Dong Pei

CHIKUNGUNYA VIRUS 2004-2025: MECHANISTIC BIOTHERMODYNAMIC MODEL OF CHIKUNGUNYA VIRUS ANTIGEN-RECEPTOR BINDING AND MULTIPLICATION DRIVEN BY GIBBS ENERGY

ABSTRACT
Chikungunya, Dengue and West Nile viruses are among the emerging arboviruses worldwide. In this research, chemical and thermodynamic properties of the Chikungunya virus were determined with the atom counting method and Patel-Erickson-Battley model, based on genetic sequences, protein sequences and virus morphology. This paper reports chemical and thermodynamic properties of the Chikungunya virus, which include molecular formulas, empirical formulas, molar masses, biosynthesis reactions, as well as thermodynamic properties of live matter, biosynthesis and antigen-receptor binding. Moreover, a mechanistic model was developed of pathogenesis during infection with Chikungunya virus. The mechanistic model is based on chemical and nonequilbrium thermodynamics. Based on the mechanistic model, an explanation is given why certain symptoms appear in Dengue infections, while other symptoms appear in Chikungunya infections, even though both are arboviruses. This methodology allows application of omics data to analyze virus-host interactions.
KEYWORDS
thermodynamics, enthalpy, entropy, Molecular formula, empirical formula, Thermochemical equations, Biosynthesis, Susceptibility, Permissiveness, Virus-host interaction
PAPER SUBMITTED: 2025-07-29
PAPER REVISED: 2025-11-01
PAPER ACCEPTED: 2025-11-10
PUBLISHED ONLINE: 2025-12-06
DOI REFERENCE: https://doi.org/10.2298/TSCI250729209P
REFERENCES
[1] Ozilgen, M., Sorguven Oner, E. Biothermodynamics: Principles and Applications (1st ed.). CRC Press, USA, 2016., 10.1201/9781315374147
[2] Popović, M. E. et al., (R)evolution of Viruses: Introduction to biothermodynamics of viruses. Virology, 603 (2025), 110319., 10.1016/j.virol.2024.110319
[3] Popović, M.E. et al., Biothermodynamic analysis of the Dengue virus: empirical formulas, biosynthesis reactions and thermodynamic properties of antigen-receptor binding and biosynthesis. Microbial Risk Analysis, 27-28 (2024), 100326., 10.1016/j.mran.2024.100326
[4] Gould, E. et al., Emerging arboviruses: Why today?. One health (Amsterdam, Netherlands), 4 (2017), 1-13., 10.1016/j.onehlt.2017.06.001
[5] Riedel, S. et al., Jawetz, Melnick and Adelberg's Medical Microbiology, 28th ed. McGraw-Hill, New York, USA, 2019. ISBN-13: 978-1260012026
[6] Wong, K. Z., Chu, J. J. H., The Interplay of Viral and Host Factors in Chikungunya Virus Infection: Targets for Antiviral Strategies. Viruses, 10 (2018), 6, 294., 10.3390/v10060294
[7] Chamberlain, J. et al., Attenuation of Chikungunya Virus by a Single Amino Acid Substitution in the nsP1 Component of a Non-Structural Polyprotein. Viruses, 17 (2025), 2, 281., 10.3390/v17020281
[8] Sharma, R. et al., Structure-function insights into chikungunya virus capsid protein: Small molecules targeting capsid hydrophobic pocket. Virology, 515 (2018), 223-234., 10.1016/j.virol.2017.12.020
[9] Mangala Prasad, V. et al., Visualization of conformational changes and membrane remodeling leading to genome delivery by viral class-II fusion machinery. Nature Communications, 13 (2022), 4772., 10.1038/s41467-022-32431-9
[10] Constant, L. E. C. et al., Overview on Chikungunya Virus Infection: From Epidemiology to State-of-the-Art Experimental Models. Frontiers in microbiology, 12 (2021), 744164., 10.3389/fmicb.2021.744164
[11] Basore, K. et al., Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor. Cell, 177 (2019), 7, 1725-1737.e16., 10.1016/j.cell.2019.04.006
[12] Monteiro, V. V. S. et al., Aedes-Chikungunya Virus Interaction: Key Role of Vector Midguts Microbiota and Its Saliva in the Host Infection. Frontiers in microbiology, 10 (2019), 492., 10.3389/fmicb.2019.00492
[13] Schwartz, O., Albert, M. Biology and pathogenesis of chikungunya virus. Nature Reviews Microbiology, 8 (2010), 491-500., 10.1038/nrmicro2368
[14] Salomão, N. G. et al., Chikungunya virus infection in the skin: histopathology and cutaneous immunological response. Frontiers in microbiology, 16 (2025), 1497354., 10.3389/fmicb.2025.1497354
[15] Paul, B. J., Sadanand, S. Chikungunya Infection: A Re-emerging Epidemic. Rheumatology and therapy, 5 (2018), 2, 317-326., 10.1007/s40744-018-0121-7
[16] Freppel, W. et al., Pathogenicity and virulence of chikungunya virus. Virulence, 15 (2024), 1, 2396484., 10.1080/21505594.2024.2396484
[17] Sharp, T. M. et al., Clinical Characteristics, Histopathology, and Tissue Immunolocalization of Chikungunya Virus Antigen in Fatal Cases. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 73 (2021), 2, e345-e354., 10.1093/cid/ciaa837
[18] Beltrán-Silva, S. L. et al., Clinical and differential diagnosis: Dengue, chikungunya and Zika. Revista Médica del Hospital General de México, 81 (2018), 3, 146-153., 10.1016/j.hgmx.2016.09.011
[19] Sayers, E. W. et al., Database resources of the National Center for Biotechnology Information. Nucleic acids research, 52 (2024), D1, D33-D43., 10.1093/nar/gkad1044
[20] Khan, A. H. et al., Complete nucleotide sequence of chikungunya virus and evidence for an internal polyadenylation site. The Journal of general virology, 83 (2002), Pt 12, 3075-3084., 10.1099/0022-1317-83-12-3075
[21] ***, NCBI: Genome assembly ViralProj14998 (NCBI RefSeq assembly: GCF_000854045.1), www.ncbi.nlm.nih.gov/datasets/genome/GCF_000854045.1/
[22] UniProt Consortium, UniProt: the Universal Protein Knowledgebase in 2025. Nucleic acids research, 53 (2025), D1, D609-D617., 10.1093/nar/gkae1010
[23] ***, Q5XXP3 · POLS_CHIK3: Structural polyprotein, www.uniprot.org/uniprotkb/Q5XXP3/entry
[24] Vanlandingham, D. L. et al., Differential infectivities of o'nyong-nyong and chikungunya virus isolates in Anopheles gambiae and Aedes aegypti mosquitoes. The American journal of tropical medicine and hygiene, 72 (2005), 5, 616-621., 10.4269/ajtmh.2005.72.616
[25] Yap, M. L. et al., Structural studies of Chikungunya virus maturation. Proceedings of the National Academy of Sciences of the United States of America, 114 (2017), 52, 13703-13707., 10.1073/pnas.1713166114
[26] Reis, E. V. S. et al., In-Depth Characterization of the Chikungunya Virus Replication Cycle. Journal of virology, 96 (2022), 3, e0173221., 10.1128/JVI.01732-21
[27] Popovic, M. et al., Death from the Nile: Empirical formula, molar mass, biosynthesis reaction and Gibbs energy of biosynthesis of the West Nile virus. Microbial Risk Analysis, 25 (2023), 100281., 10.1016/j.mran.2023.100281
[28] Popović, M. et al., Breaking news: Empirical formulas, molar masses, biosynthesis reactions, and thermodynamic properties of virus particles, biosynthesis and binding of Omicron JN.1 variant of SARS-CoV-2. Journal of the Serbian Chemical Society, 89 (2024), 3, 305-320., 10.2298/JSC240119019P
[29] Popović, M.E. et al., Like a summer storm: Biothermodynamic analysis of Rotavirus A - Empirical formula, biosynthesis reaction and driving force of virus multiplication and antigen-receptor binding. Microbial Risk Analysis, 26 (2024), 100291., 10.1016/j.mran.2024.100291
[30] Popović, M.E. et al., The silent assassin: Empirical formulas, molar masses, biosynthesis reactions, enthalpies, entropies and Gibbs energies of biosynthesis and Gibbs energies of binding of Coxsackieviruses A and B. Thermal Science, 28 (2024), 6A, 4737-4757., 10.2298/TSCI240429213P
[31] Popovic, M. et al., Thermodynamics of microbial consortia: Enthalpies and Gibbs energies of microorganism live matter and macromolecules of E. coli, G. oxydans, P. fluorescens, S. thermophilus and P. chrysogenum. Journal of Biotechnology, 379 (2024), 6-17., 10.1016/j.jbiotec.2023.11.001
[32] Battley, E.H., The development of direct and indirect methods for the study of the thermodynamics of microbial growth. Thermochimica Acta, 309 (1998), 1-2, 17-37., 10.1016/S0040-6031(97)00357-2
[33] Popovic, M., Thermodynamic properties of microorganisms: determination and analysis of enthalpy, entropy, and Gibbs free energy of biomass, cells and colonies of 32 microorganism species. Helyon, 5 (2019), 6, e01950., 10.1016/j.heliyon.2019.e01950
[34] Popovic, M., Minceva, M., Thermodynamic properties of human tissues. Thermal Science, 24 (2020), 6B, 4115-4133., 10.2298/TSCI200109151P
[35] Popović, M.E. et al., Eris - another brick in the wall: Empirical formulas, molar masses, biosynthesis reactions, enthalpy, entropy and Gibbs energy of Omicron EG.5 Eris and EG.5.1 variants of SARS-CoV-2. Microbial Risk Analysis, 25 (2023), 100280., 10.1016/j.mran.2023.100280
[36] Popovic, M., Why doesn't Ebola virus cause pandemics like SARS-CoV-2? Microbial Risk Analysis, 22 (2022), 100236., 10.1016/j.mran.2022.100236
[37] Popovic, M., Atom counting method for determining elemental composition of viruses and its applications in biothermodynamics and environmental science. Computational Biology and Chemistry, 96 (2022), 107621., 10.1016/j.compbiolchem.2022.107621
[38] Rippe K. Making contacts on a nucleic acid polymer. Trends in biochemical sciences, 26 (2001), 12, 733-740., 10.1016/s0968-0004(01)01978-8
[39] Patel, S.A., Erickson, L.E., Estimation of heats of combustion of biomass from elemental analysis using available electron concepts. Biotechnology and Bioengineering, 23 (1981), 2051-2067., 10.1002/bit.260230910
[40] Battley, E.H., An empirical method for estimating the entropy of formation and the absolute entropy of dried microbial biomass for use in studies on the thermodynamics of microbial growth. Thermochimica Acta, 326 (1999), 1-2, 7-15., 10.1016/S0040-6031(98)00584-X
[41] Atkins, P. W., de Paula, J., Physical Chemistry for the Life Sciences (2nd edition), W. H. Freeman and Company, New York, USA, 2011. ISBN-13: 978-1429231145
[42] Du, X. et al., Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods. International journal of molecular sciences, 17 (2016), 2, 144., 10.3390/ijms17020144
[43] Wimmer E., The test-tube synthesis of a chemical called poliovirus. The simple synthesis of a virus has far-reaching societal implications. EMBO reports, 7 (2006), Special Number, S3-S9., 10.1038/sj.embor.7400728
[44] Degueldre C., Single virus inductively coupled plasma mass spectroscopy analysis: A comprehensive study. Talanta, 228 (2021), 122211., 10.1016/j.talanta.2021.122211
[45] te Velthuis, A.J.W. et al., Structural insights into RNA polymerases of negative-sense RNA viruses. Nat Rev Microbiol 19 (2021), 303-318., 10.1038/s41579-020-00501-8
[46] Ambroggio, E. E. et al., Dengue and Zika virus capsid proteins bind to membranes and self-assemble into liquid droplets with nucleic acids. The Journal of biological chemistry, 297 (2021), 3, 101059., 10.1016/j.jbc.2021.101059
[47] Wu, D. et al., Polymerization in living organisms. Chemical Society reviews, 52 (2023), 9, 2911-2945., 10.1039/d2cs00759b
[48] Newman, L.E. et al., Mitochondrial DNA replication stress triggers a pro-inflammatory endosomal pathway of nucleoid disposal. Nat Cell Biol, 26 (2024), 194-206., 10.1038/s41556-023-01343-1
[49] Cojocaru, R., Unrau, P. J., Processive RNA polymerization and promoter recognition in an RNA World. Science (New York, N.Y.), 371 (2021), 6535, 1225-1232., 10.1126/science.abd9191
[50] Du, S. et al., d-Amino acids in biological systems. Chirality, 35 (2023), 9, 508-534., 10.1002/chir.23562
[51] Katen, S., Zlotnick, A. The thermodynamics of virus capsid assembly. Methods in enzymology, 455 (2009), 395-417., 10.1016/S0076-6879(08)04214-6
[52] Demirel, Y. Nonequilibrium Thermodynamics: Transport and Rate Processes in Physical, Chemical and Biological Systems, 3rd ed., Elsevier, Amsterdam, Netherlands, 2014. ISBN: 9780444595812
[53] Von Stockar, U.. Biothermodynamics of live cells: energy dissipation and heat generation in cellular structures. In: Biothermodynamics: the role of thermodynamics in Biochemical Engineering (von Stockar, U., ed.) EPFL Press, Lausanne, Switzerland, 2013, pp. 475-534., 10.1201/b15428
[54] Duponchel, S., Fischer, M. G., Viva lavidaviruses! Five features of virophages that parasitize giant DNA viruses. PLoS pathogens, 15 (2019), 3, e1007592., 10.1371/journal.ppat.1007592
[55] Gazi, U., Martinez-Pomares, L., Influence of the mannose receptor in host immune responses. Immunobiology, 214 (2009), 7, 554-561., 10.1016/j.imbio.2008.11.004
[56] ***, Reuters: World Health Organization raises concern about spread of mosquito-borne Chikungunya virus, www.reuters.com/business/healthcare-pharmaceuticals/world-health-organization-raises-concern-about-spread-mosquito-borne-chikungunya-2025-07-22/
[57] ***, ECDC: Chikungunya virus disease worldwide overview, Situation update, June 2025, www.ecdc.europa.eu/en/chikungunya-monthly
[58] Zumla et al., Chikungunya virus disease returns to Europe: a turning point for the global arboviral landscape, The Lancet, (2025)., 10.1016/S0140-6736(25)01458-8
PDF VERSION [DOWNLOAD]
Chikungunya virus 2004-2025: Mechanistic biothermodynamic model of Chikungunya virus antigen-receptor binding and multiplication driven by gibbs energy

© 2026 Society of Thermal Engineers of Serbia. Published by the Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Belgrade, Serbia. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International licence