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<p>Acute respiratory distress syndrome (ARDS) is the leading cause of mortality in pathogen-mediated lung inflammation. Viral-induced cytokine release syndrome (CRS) has emerged as a global pandemic, characterized by a hyperactive immune response and excessive cytokine production causing irreversible lung injury. This study aimed to evaluate FDA-approved drugs for their potential to target hyperactive immune response and SARS-CoV-2 viral replication simultaneously. Six potential 3-CL<sup>pro</sup> inhibitors were identified by molecular docking using MOE software, including ebastine (<b>1</b>), orlistat (<b>2</b>), atracurium besylate (<b>3</b>), piperaquine phosphate (<b>4</b>), valsartan (<b>5</b>), and acarbose (<b>6</b>), among which <b>1</b>–<b>3</b> binds strongly to the target protein with binding affinity of − 8.22, − 9.12, and − 7.81, kcal/mol, respectively. Additionally, all identified inhibitors except <b>4</b> revealed significant anti-viral potential, with a 50–100% reduction in SARS-CoV-2 plaques. Significant attenuation of phagocyte oxidative burst and inflammatory cytokines (IFN-γ, GM-CSF, IL-6, IL-2, IL-1β, TNF-α) demonstrated the immunomodulatory potential of these drugs. This study demonstrates the potential of pre-existing drugs to ameliorate the cytokine storm and oxidative damage with simultaneous anti-viral effects. The data provide pre-clinical support to develop these drugs as potential therapeutic agent against ARDS.</p>

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Identification of effective synthetic molecules against viral-induced cytokine release syndrome using in silico and in vitro approaches

  • 期刊论文

  • 发表日期：

    2025年2月25日

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  • Hira Noor Malik,
  • Almas Jabeen,
  • Sajda Ashraf,
  • Saba Farooq,
  • Hana’a Iqbal,
  • Zaheer Ul-Haq

摘要

Acute respiratory distress syndrome (ARDS) is the leading cause of mortality in pathogen-mediated lung inflammation. Viral-induced cytokine release syndrome (CRS) has emerged as a global pandemic, characterized by a hyperactive immune response and excessive cytokine production causing irreversible lung injury. This study aimed to evaluate FDA-approved drugs for their potential to target hyperactive immune response and SARS-CoV-2 viral replication simultaneously. Six potential 3-CLpro inhibitors were identified by molecular docking using MOE software, including ebastine (1), orlistat (2), atracurium besylate (3), piperaquine phosphate (4), valsartan (5), and acarbose (6), among which 1–3 binds strongly to the target protein with binding affinity of − 8.22, − 9.12, and − 7.81, kcal/mol, respectively. Additionally, all identified inhibitors except 4 revealed significant anti-viral potential, with a 50–100% reduction in SARS-CoV-2 plaques. Significant attenuation of phagocyte oxidative burst and inflammatory cytokines (IFN-γ, GM-CSF, IL-6, IL-2, IL-1β, TNF-α) demonstrated the immunomodulatory potential of these drugs. This study demonstrates the potential of pre-existing drugs to ameliorate the cytokine storm and oxidative damage with simultaneous anti-viral effects. The data provide pre-clinical support to develop these drugs as potential therapeutic agent against ARDS.