Synergistic antiviral effects of structure-guided peptides and a mutagenic base analog on SARS-CoV-2 replication
-fold reduction in infectious virus, achieving near-complete loss of infectivity at non-cytotoxic concentrations. Next-generation sequencing revealed that dual treatment increased mutation frequency, altered mutant spectra, and decreased genome stability, consistent with progression toward error catastrophe. Principal component analysis confirmed that combined treatment generated mutant spectra distinct from either monotherapy. These findings are consistent with a dual antiviral strategy in which structure-guided peptides designed to interact with components of the SARS-CoV-2 replication complex act in combination with lethal mutagenesis to produce a synergistic interaction between these two complementary processes. This integrated approach suggests a potential broad-spectrum antiviral strategy with applicability to other coronaviruses.
Authors
- Sergio Ortega del Campo
- Esteban Domingo (ORCID: https://orcid.org/0000-0002-0573-1676)
- Josefa Gómez Maldonado (ORCID: https://orcid.org/0000-0003-1570-1937)
- Ugo Bastolla (ORCID: https://orcid.org/0000-0001-9342-4678)
- Enrique Viguera (ORCID: https://orcid.org/0000-0001-5475-3807)
- Luis Díaz‐Martínez (ORCID: https://orcid.org/0000-0002-7659-4349)
- Celia Perales (ORCID: https://orcid.org/0000-0003-1618-1937)
- Encarnación Clavijo Frutos
- Clara Blanes‐Mira (ORCID: https://orcid.org/0000-0002-9625-6275)
- Ana Isabel de Ávila (ORCID: https://orcid.org/0000-0002-9381-0963)
- Gregorio Fernández‐Ballester (ORCID: https://orcid.org/0000-0002-5412-8611)
- Brenda Martínez‐González (ORCID: https://orcid.org/0000-0002-4482-5181)
- María Eugenia Soria (ORCID: https://orcid.org/0000-0002-4719-3351)
- Ana María Fernández‐Escamilla (ORCID: https://orcid.org/0000-0002-6615-4913)
- Ana Grande Pérez
- Francisco José Villena González (ORCID: https://orcid.org/0009-0006-9119-1093)
- Víctor Guirado Osorio
- María Isabel Viciana Ramos
- Jesús L. Santos González
Institutions
- Universitat de Miguel Hernández d'Elx (ES)
- Hospital Universitario Fundación Jiménez Díaz (ES)
- Centro de Biología Molecular Severo Ochoa (ES)
- Hospital Clínico Universitario Virgen de la Victoria (ES)
- Instituto de Investigación Biomédica de Málaga (ES)
- Universidad Autónoma de Madrid (ES)
- Universidad de Málaga (ES)
Publication Details
- Journal
- Antimicrobial Agents and Chemotherapy
- Published
- 2026-04-27
- DOI
- https://doi.org/10.1128/aac.01885-25
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fundación Ramón Areces
- Universidad de Málaga
- Comunidad de Madrid
- Ministerio de Ciencia, Innovación y Universidades
- Centro de Biología Molecular Severo Ochoa
- Generalitat Valenciana
- Junta de Andalucía
- Agencia Estatal de Investigación
- Centro Nacional de Biotecnología
- Ministerio de Universidades