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<p>Emerging pathogens such as SARS-CoV-2 are always the cause of extremely high morbidity and mortality. Despite a shared history with humanity spanning more than half a decade, COVID-19 treatment is still challenging, especially in people with comorbidities. The RBD of the S-glycoprotein is a promising target because it plays a key role in the tropism of SARS-CoV-2. Using AutoDock Vina together with a bash script FDA-approved compounds were virtually screened for their binding affinity to the RBD pocket, which was identified in our previous work. Nine promising compounds were selected based on the noncovalent interaction pattern and were studied by short molecular dynamics simulation. Bicalutamide and ketodarolutamide formed sufficiently stable complexes and were studied by longer molecular dynamics. Ketodarolutamide was the only ligand whose parameters had acceptable values for a potential RBD inhibitor. A characteristic component of both compounds was halogenated benzonitrile, which in the case of ketodarolutamide stabilized the complex. Further ELISA also partially confirmed the inhibitory effect of ketodarolutamide on the RBD/hACE2 interaction, which is consistent with known reports of a milder course of COVID-19 in patients on antiandrogen therapy. We suggest that ketodarolutamide can be considered as a promising scaffold for the development of a benzonitrile-containing RBD inhibitor.</p>

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Ketodarolutamide may interact with the receptor-binding domain of the SARS-CoV-2 spike glycoprotein: the importance of halogenated benzonitrile

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月7日

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  • Andrii Zaremba,
  • Polina Zaremba,
  • Svіtlana Zahorodnia

摘要

Emerging pathogens such as SARS-CoV-2 are always the cause of extremely high morbidity and mortality. Despite a shared history with humanity spanning more than half a decade, COVID-19 treatment is still challenging, especially in people with comorbidities. The RBD of the S-glycoprotein is a promising target because it plays a key role in the tropism of SARS-CoV-2. Using AutoDock Vina together with a bash script FDA-approved compounds were virtually screened for their binding affinity to the RBD pocket, which was identified in our previous work. Nine promising compounds were selected based on the noncovalent interaction pattern and were studied by short molecular dynamics simulation. Bicalutamide and ketodarolutamide formed sufficiently stable complexes and were studied by longer molecular dynamics. Ketodarolutamide was the only ligand whose parameters had acceptable values for a potential RBD inhibitor. A characteristic component of both compounds was halogenated benzonitrile, which in the case of ketodarolutamide stabilized the complex. Further ELISA also partially confirmed the inhibitory effect of ketodarolutamide on the RBD/hACE2 interaction, which is consistent with known reports of a milder course of COVID-19 in patients on antiandrogen therapy. We suggest that ketodarolutamide can be considered as a promising scaffold for the development of a benzonitrile-containing RBD inhibitor.