Harnessing prebiotic formamide chemistry: a novel platform for antiviral exploration

  • Sci Rep. 2025 Aug 2;15(1):28197. doi: 10.1038/s41598-025-14001-3.
Maria Grazia Martina  1 ,  Chiara Vagaggini  2 ,  Elena Dreassi  2 ,  Marta De Angelis  3  4 ,  Lucia Nencioni  3 ,  Filippo Dragoni  5 ,  Federica Giammarino  5 ,  Adele Boccuto  5 ,  Maurizio Zazzi  5 ,  Ilaria Vicenti  5 ,  Marco Radi  6
Affiliations
  • 1. Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Viale delle Scienze, 27/A, Parma, 43124, Italy.
  • 2. Department of Biotechnology, Chemistry and Pharmacy (DBCF), University of Siena, Siena, 53100, Italy.
  • 3. Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, P.le Aldo Moro 5, Rome, 00185, Italy.
  • 4. Laboratory of Virology, Department of Molecular Medicine, Sapienza University, Rome, 00185, Italy.
  • 5. Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, Siena, 53100, Italy.
  • 6. Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Viale delle Scienze, 27/A, Parma, 43124, Italy. [email protected].
PMID: 40750837 DOI: 10.1038/s41598-025-14001-3
Abstract

Viruses and host cells are intricately connected through a shared "chemical language" that may trace back to the prebiotic chemistry of early Earth. In this study, we present an innovative platform for Antiviral exploration inspired by this primordial chemical framework. By "doping" the formamide-based prebiotic chemistry model with orotic acid derivatives, we generated complex, non-natural chemical mixtures capable of disrupting the replication of multiple viruses with minimal or no toxicity for eukaryotic cells. This strategy underscores the potential of an evolution-inspired approach in Antiviral discovery, offering a novel avenue for identifying new agents with unconventional mechanisms that might elude traditional discovery methods.

Keywords
Antiviral activity; Co-evolution; Complexity; Formamide model; Prebiotic chemistry.
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