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<p>Dengue viruses (DENVs) usually cause a mild febrile illness which might flare up in some patients as dengue haemorrhagic fever (DHF) or dengue shock syndrome. Altered expression of autoimmune markers and development of autoimmune diseases was observed in patients exhibiting prolonged dengue symptoms, suggesting a possible correlation between DENVs and autoimmune diseases. Molecular mimicry of the blood coagulation pathway proteins by DENVs might be a potential factor underlying clinical manifestations of DHF. Inhibition of protein-protein interactions (PPIs) in DENV mimicry proteins and human proteins can potentially treat both DHF and, associated autoimmune diseases. In this study, we have performed a systematic in silico analysis of human proteins interacting with DENV mimicry proteins (HPIDMP) as novel drug targets. Potential inhibitors of the HPIDMP were discerned from the DrugBank database following stringent parameters. The protein–ligand interactions were predicted using molecular docking and evaluated with decoy-based validation, molecular dynamics simulations, and MM-PBSA binding free energy calculations. RAF1 targeting drugs Sorafenib and Regorafenib exhibited the most consistent interaction profile across all computational analyses, followed by the SIRT1-targeting compounds selisistat and resveratrol, which demonstrated moderate but consistent computational support. In contrast, the MYH9–artenimol and HSPE1–phenethyl isothiocyanate systems showed comparatively weaker support. On the basis of our results, we propose Sorafenib and Regorafenib as the most promising candidates for in vitro or clinical studies for treatment of DHF and/or DENV-associated autoimmune diseases, followed by Selisistat and Resveratrol. Thus these DrugBank molecules can be incorporated in clinical studies or in vitro testing for treatment of DHF and/or DENV-associated autoimmune diseases. Also, the methods adopted in this study can guide the repurposing of known drugs to treat other pathogen-associated autoimmune diseases.</p> Graphical abstract <p></p>

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Repurposing drugs for treating dengue haemorrhagic fever and associated autoimmune diseases

  • 期刊论文

  • 发表日期：

    2026年7月31日

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  • Govinda Rao Dabburu,
  • Anjali Garg,
  • Anchal Vishnoi,
  • Neelja Singhal,
  • Manish Kumar

摘要

Dengue viruses (DENVs) usually cause a mild febrile illness which might flare up in some patients as dengue haemorrhagic fever (DHF) or dengue shock syndrome. Altered expression of autoimmune markers and development of autoimmune diseases was observed in patients exhibiting prolonged dengue symptoms, suggesting a possible correlation between DENVs and autoimmune diseases. Molecular mimicry of the blood coagulation pathway proteins by DENVs might be a potential factor underlying clinical manifestations of DHF. Inhibition of protein-protein interactions (PPIs) in DENV mimicry proteins and human proteins can potentially treat both DHF and, associated autoimmune diseases. In this study, we have performed a systematic in silico analysis of human proteins interacting with DENV mimicry proteins (HPIDMP) as novel drug targets. Potential inhibitors of the HPIDMP were discerned from the DrugBank database following stringent parameters. The protein–ligand interactions were predicted using molecular docking and evaluated with decoy-based validation, molecular dynamics simulations, and MM-PBSA binding free energy calculations. RAF1 targeting drugs Sorafenib and Regorafenib exhibited the most consistent interaction profile across all computational analyses, followed by the SIRT1-targeting compounds selisistat and resveratrol, which demonstrated moderate but consistent computational support. In contrast, the MYH9–artenimol and HSPE1–phenethyl isothiocyanate systems showed comparatively weaker support. On the basis of our results, we propose Sorafenib and Regorafenib as the most promising candidates for in vitro or clinical studies for treatment of DHF and/or DENV-associated autoimmune diseases, followed by Selisistat and Resveratrol. Thus these DrugBank molecules can be incorporated in clinical studies or in vitro testing for treatment of DHF and/or DENV-associated autoimmune diseases. Also, the methods adopted in this study can guide the repurposing of known drugs to treat other pathogen-associated autoimmune diseases.

Graphical abstract