{
  "abstract": "SARS-CoV-2 has undergone rapid genetic evolution, leading to the emergence of new variants with distinct mutations impacting global public health. Upon infection, the virus triggers a robust inflammatory response characterized by the release of pro-inflammatory cytokines, which play a central role in lung injury. It also alters the host antioxidant response, causing oxidative stress that supports viral replication and cytokine overproduction. This study investigated key pathogenic effectors in Calu-3 and A549-ACE2/TMPRSS2 cells infected with SARS-CoV-2 variants, focusing on replication kinetics, cellular redox state, and inflammatory cytokine profile. A dramatic redox alteration in terms of glutathione (GSH) and Cysteine (Cys) was observed at 48 h p.i., along with a strong pro-inflammatory cytokine response , likely via activation of the JNK/AP-1 signaling pathway. To counteract these effects, two thiol molecules were tested: I-152, a monothiol conjugate of N-Acetyl-Cysteine (NAC) and β-mercaptoethylamine (MEA) and its dithiol derivative, I-152SdAc. Thiols restored GSH balance by enhancing the expression of Nrf2-mediated genes, such as glutamate-Cys ligase modifier subunit (GCLM), and counteracted AP-1-mediated pathway, resulting in a significant reduction of inflammation and viral replication. Antiviral and anti-inflammatory activities of thiols were confirmed in NHBE cells. These findings highlight that redox imbalance is a key pathogenetic event in SARS-CoV-2 infection. Notably, besides Nrf2 and AP-1, other redox-sensitive factors, such as the CHAC glutathione-specific gamma-glutamyl-cyclotransferase 1 (CHAC1), seem to contribute to the pathogenesis and may represent a new potential therapeutic target of redox active compounds. Therefore, the thiol-derived molecules act as broadly effective compounds by limiting virus replication and inflammation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University, Rome, Italy",
    "Laboratory of Virology, Department of Molecular Medicine, Sapienza University, Rome, Lazio, Italy",
    "Department of Medical Biotechnologies, Policlinico Santa Maria delle Scotte, University of Siena, Siena, Italy",
    "Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy",
    "Department of Infectious Diseases, Istituto Superiore Di Sanità, Rome, Italy"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Marta De Angelis",
      "orcid": "0000-0002-1916-6508"
    },
    {
      "affs": [
        2
      ],
      "name": "Gianni Gori Savellini",
      "orcid": "0000-0003-2287-9258"
    },
    {
      "affs": [
        0
      ],
      "name": "Elena Piselli"
    },
    {
      "affs": [
        2
      ],
      "name": "Gabriele Anichini"
    },
    {
      "affs": [
        0
      ],
      "name": "Giulia Radocchia"
    },
    {
      "affs": [
        3
      ],
      "name": "Sofia Masini"
    },
    {
      "affs": [
        3
      ],
      "name": "Francesca Monittola"
    },
    {
      "affs": [
        3
      ],
      "name": "Francesca Bartoccini",
      "orcid": "0000-0003-0400-7771"
    },
    {
      "affs": [
        3
      ],
      "name": "Michela Bruschi"
    },
    {
      "affs": [
        3
      ],
      "name": "Mauro Magnani"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Anna Teresa Palamara"
    },
    {
      "affs": [
        2
      ],
      "name": "Maria Grazia Cusi"
    },
    {
      "affs": [
        3
      ],
      "name": "Rita Crinelli"
    },
    {
      "affs": [
        3
      ],
      "name": "Alessandra Fraternale",
      "orcid": "0000-0002-7893-3842"
    },
    {
      "affs": [
        0
      ],
      "name": "Lucia Nencioni",
      "orcid": "0000-0003-4427-4823"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6gptshmzbvrqk.bib",
  "cited_by": 0,
  "doi": "10.1128/aac.00518-26",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13712884/",
  "id": "6gptshmzbvrqk",
  "issns": [
    "0066-4804",
    "1098-6596"
  ],
  "landing_url": "https://doi.org/10.1128/aac.00518-26",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Antiviral Agents"
    ],
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7171740453",
  "pdf_url": "https://journals.asm.org/doi/pdf/10.1128/aac.00518-26?download=true",
  "pmcid": "PMC13712884",
  "pmid": "42524834",
  "published": "2026-07-29",
  "publisher": "American Society for Microbiology (ASM)",
  "ris": "https://research.draconitic.com/paper/6gptshmzbvrqk.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:23:23Z",
      "native_id": "PMC13712884",
      "source": "pmc",
      "url": "https://doi.org/10.1128/aac.00518-26"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|SARS-CoV-2 and COVID-19 Research",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Redox-sensitive factors as targets of thiol compounds to hinder SARS-CoV-2 replication and inflammatory response",
  "title_text": "Redox-sensitive factors as targets of thiol compounds to hinder SARS-CoV-2 replication and inflammatory response",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:23:23Z",
  "url": "https://research.draconitic.com/paper/6gptshmzbvrqk",
  "venue": "Antimicrobial Agents and Chemotherapy",
  "versions": []
}