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<p>Dengue is a frequent mosquito borne infection with no antiviral medications approved and drug repurposing is an economical and time-saving method of creating an efficient therapy. This research has chosen RNA-dependent RNA polymerase (RdRp) of non-structural protein 5 (NS5) of dengue virus serotype 2 (DENV-2) as a therapeutic. PyRx software was used to perform virtual screening of FDA-approved drugs available in the ZINC database based on their structure. Out of the top15, doxorubicin and rifamycin were selected as candidate drugs to undergo molecular docking and molecular dynamics (MD) studies. Docking showed binding energies of − 8.9&#xa0;kcal/mol for doxorubicin and − 8.6&#xa0;kcal/mol for rifamycin. Simulations of MD confirmed that interactions of doxorubicin with the palm domain of RdRp occur in a stable way, which may result in the inability to promote viral replication. In Vero cells, cytotoxicity tests showed that concentrations below 12.25&#xa0;µg/mL of doxorubicin were not toxic, whereas higher concentrations had morphological effects with a CC<sub>50</sub> of approximately 150&#xa0;µg/mL. MTT-based cell viability assays in DENV-2–infected Vero cells showed dose-dependent effects on cell viability, with an IC<sub>50</sub> of 86.52&#xa0;µg/mL. Conclusively, doxorubicin exhibited indirect, cell viability–based effects in DENV-2–infected Vero cells at non-cytotoxic concentrations, however, a low selectivity index (SI ≈ 1.7) and cytotoxicity highlights a narrow therapeutic window, limiting its potential for direct clinical use. The development of safer derivatives, optimized dosing and targeted delivery systems, e.g., nanocarriers should be considered in future research to improve efficacy and decrease toxicity.</p>

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In Silico and in vitro antiviral activity of FDA approved drugs from ZINC database against RNA-dependent RNA polymerase of dengue virus

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月19日

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  • Alia Uzma,
  • Adiba,
  • Ammara Kausar,
  • Muhammad Waseem Aslam,
  • Liaqat Ali,
  • Mahwish Ali,
  • Asma Saleem Qazi,
  • Abdul Haq,
  • Deeba Amraiz,
  • Emad Rashad Sindi,
  • Taha Alqahtani,
  • Magdi E. A. Zaki,
  • Molalign Assefa

摘要

Dengue is a frequent mosquito borne infection with no antiviral medications approved and drug repurposing is an economical and time-saving method of creating an efficient therapy. This research has chosen RNA-dependent RNA polymerase (RdRp) of non-structural protein 5 (NS5) of dengue virus serotype 2 (DENV-2) as a therapeutic. PyRx software was used to perform virtual screening of FDA-approved drugs available in the ZINC database based on their structure. Out of the top15, doxorubicin and rifamycin were selected as candidate drugs to undergo molecular docking and molecular dynamics (MD) studies. Docking showed binding energies of − 8.9 kcal/mol for doxorubicin and − 8.6 kcal/mol for rifamycin. Simulations of MD confirmed that interactions of doxorubicin with the palm domain of RdRp occur in a stable way, which may result in the inability to promote viral replication. In Vero cells, cytotoxicity tests showed that concentrations below 12.25 µg/mL of doxorubicin were not toxic, whereas higher concentrations had morphological effects with a CC50 of approximately 150 µg/mL. MTT-based cell viability assays in DENV-2–infected Vero cells showed dose-dependent effects on cell viability, with an IC50 of 86.52 µg/mL. Conclusively, doxorubicin exhibited indirect, cell viability–based effects in DENV-2–infected Vero cells at non-cytotoxic concentrations, however, a low selectivity index (SI ≈ 1.7) and cytotoxicity highlights a narrow therapeutic window, limiting its potential for direct clinical use. The development of safer derivatives, optimized dosing and targeted delivery systems, e.g., nanocarriers should be considered in future research to improve efficacy and decrease toxicity.