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<p>Considering the risk of potential future outbreaks similar to the COVID-19 pandemic, this study highlights the importance of repurposing in silico drugs as a proactive approach. We report the findings from docking drug libraries onto three key drug targets of SARS-CoV-2: nsp15 Endoribonuclease, main protease, and the nsp16-nsp10 complex. This study evaluated 128 viral compounds, including 89 FDA-approved drugs and 39 phytocompounds. The molecular docking was conducted using the reliable and licensed Schrödinger tool. The results were assessed through glide scores and energy (kcal/mol). The virtual screening identified remdesivir, ribavirin, and letermovir as leading candidates for targeting nsp15 in SARS-CoV-2. Similarly, adefovir, entecavir, and penciclovir emerged as promising leads against the main protease, while vidarabine, tenofovir, fosamprenavir, zidovudine, and saquinavir were highlighted as potential inhibitors of the SAM binding site of the nsp16-nsp10 complex. Notably, zidovudine exhibited a lower binding energy (-80.07&#xa0;kcal/mol) at the SAM site than SAM (76.49&#xa0;kcal/mol), indicating binding solid potential. Among the screened phytocompounds, apigenin, quercetin, silymarin, amentoflavone, hippomannin A, saikosaponin B2, ent-epiafzelechin, epigallocatechin, and chebulagic acid showed significant interactions with the selected SARS-CoV-2 proteins. Notably, the glide scores of epigallocatechin (-7.596), amentoflavone (-7.417), and quercetin (-7.408) suggest a stronger affinity for nsp15 than even remdesivir (-7.22). The results emphasize the potential of drug repurposing in quickly identifying effective therapeutic options during future viral outbreaks. This work demonstrates that repurposing existing drugs, especially those with known safety profiles, can be a vital strategy to expedite treatment availability and reduce the impact of emerging infectious diseases.</p>

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Drug repurposing in silico screening of antiviral drugs and evidence-based plant-derived anti-oxidant molecules targeting nsp15, main protease, and nsp16-nsp10 complex of SARS-CoV-2: strategic insights for managing future recurrence

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月14日

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  • Triveni Singirisetty,
  • Naresh Babu Chilamakuru,
  • Anoop Bodapati,
  • Sudha Divya Madhuri Kallam,
  • Selvankumar Thangaswamy,
  • Vinod Kumar Nelson,
  • Punna Rao Suryadevara

摘要

Considering the risk of potential future outbreaks similar to the COVID-19 pandemic, this study highlights the importance of repurposing in silico drugs as a proactive approach. We report the findings from docking drug libraries onto three key drug targets of SARS-CoV-2: nsp15 Endoribonuclease, main protease, and the nsp16-nsp10 complex. This study evaluated 128 viral compounds, including 89 FDA-approved drugs and 39 phytocompounds. The molecular docking was conducted using the reliable and licensed Schrödinger tool. The results were assessed through glide scores and energy (kcal/mol). The virtual screening identified remdesivir, ribavirin, and letermovir as leading candidates for targeting nsp15 in SARS-CoV-2. Similarly, adefovir, entecavir, and penciclovir emerged as promising leads against the main protease, while vidarabine, tenofovir, fosamprenavir, zidovudine, and saquinavir were highlighted as potential inhibitors of the SAM binding site of the nsp16-nsp10 complex. Notably, zidovudine exhibited a lower binding energy (-80.07 kcal/mol) at the SAM site than SAM (76.49 kcal/mol), indicating binding solid potential. Among the screened phytocompounds, apigenin, quercetin, silymarin, amentoflavone, hippomannin A, saikosaponin B2, ent-epiafzelechin, epigallocatechin, and chebulagic acid showed significant interactions with the selected SARS-CoV-2 proteins. Notably, the glide scores of epigallocatechin (-7.596), amentoflavone (-7.417), and quercetin (-7.408) suggest a stronger affinity for nsp15 than even remdesivir (-7.22). The results emphasize the potential of drug repurposing in quickly identifying effective therapeutic options during future viral outbreaks. This work demonstrates that repurposing existing drugs, especially those with known safety profiles, can be a vital strategy to expedite treatment availability and reduce the impact of emerging infectious diseases.