2. Academic Validation
  3. Identification of nsp16 inhibitors of SARS -CoV-2, SARS -CoV-1 and MERS-CoV from FDA-approved drugs using in silico and in vitro methods

Identification of nsp16 inhibitors of SARS -CoV-2, SARS -CoV-1 and MERS-CoV from FDA-approved drugs using in silico and in vitro methods

  • Biomed Pharmacother. 2025 Aug:189:118246. doi: 10.1016/j.biopha.2025.118246.
Ejlal A Omer 1,  Sara Abdelfatah 1,  Nasim Shahhamzehei 1,  Axel Guthart 1,  Kathrin Sutter 2,  Hannah S Schwarzer-Sperber 3,  Roland Schwarzer 4,  Thomas Efferth 5
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, Mainz 55128, Germany.
  • 2 Institute for Virology, University Hospital Essen, University Duisburg-Essen, Essen, Germany; Institute for the Research on HIV and AIDS-associated Diseases (HIV-AAD), University Hospital Essen, University Duisburg-Essen, Essen, Germany.
  • 3 Institute for Virology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
  • 4 Institute for the Research on HIV and AIDS-associated Diseases (HIV-AAD), University Hospital Essen, University Duisburg-Essen, Essen, Germany. Electronic address: Roland.Schwarzer@uk-essen.de.
  • 5 Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, Mainz 55128, Germany. Electronic address: efferth@uni-mainz.de.
PMID: 40543162 DOI: 10.1016/j.biopha.2025.118246
Abstract

The methyltransferase nsp16 is a key enzyme that catalyses coronavirus replication. In this study, we virtually screened 1577 FDA-approved drugs against nsp16 of SARS-CoV-2, SARS-CoV-1, and MERS-CoV to identify compounds potentially serving as pan-coronavirus inhibitors. Microscale thermophoresis (MST) was used to verify the in-silico results obtained by virtual drug screening, followed by molecular docking and molecular dynamics simulation to test the binding affinities between the target and the candidates. Finally, the candidates were tested against a clinical isolate of SARS-CoV-2 in Cell Culture. The MST binding assay and molecular docking results showed that four of the candidates showed strong binding affinities to nsp16 of one or two coronaviruses. Nilotinib and simeprevir interacted with nsp16 protein of all three coronaviruses, viz., SARS-CoV-2, SARS-CoV-1, and MERS-CoV, suggesting their potential to act as pan-coronavirus inhibitors. The drugs inhibited the virus with IC50 values ranging between 8.34 and 36.1 µM when tested against a clinical isolate of SARS-CoV-2 in Cell Culture.

Keywords

FDA-approved drugs; Nsp16; Pan-coronavirus inhibitors; SARS-CoV-2.

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