tetano
Editor, Senior Moderator
Biomed Pharmacother
. 2025 Jun 20:189:118246.
doi: 10.1016/j.biopha.2025.118246. Online ahead of print. 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
Ejlal A Omer[SUP] 1 [/SUP], Sara Abdelfatah[SUP] 1 [/SUP], Nasim Shahhamzehei[SUP] 1 [/SUP], Axel Guthart[SUP] 1 [/SUP], Kathrin Sutter[SUP] 2 [/SUP], Hannah S Schwarzer-Sperber[SUP] 3 [/SUP], Roland Schwarzer[SUP] 4 [/SUP], Thomas Efferth[SUP] 5 [/SUP]
Affiliations
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 IC[SUB]50[/SUB] 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.
. 2025 Jun 20:189:118246.
doi: 10.1016/j.biopha.2025.118246. Online ahead of print. 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
Ejlal A Omer[SUP] 1 [/SUP], Sara Abdelfatah[SUP] 1 [/SUP], Nasim Shahhamzehei[SUP] 1 [/SUP], Axel Guthart[SUP] 1 [/SUP], Kathrin Sutter[SUP] 2 [/SUP], Hannah S Schwarzer-Sperber[SUP] 3 [/SUP], Roland Schwarzer[SUP] 4 [/SUP], Thomas Efferth[SUP] 5 [/SUP]
Affiliations
- PMID: 40543162
- DOI: 10.1016/j.biopha.2025.118246
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 IC[SUB]50[/SUB] 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.