There is an urgent need of effective drugs for the treatment of the SARS-CoV-2 infection. Remdesivir (Veklury®), a nucleotide analogue, is the only drug that was approved by FDA on October 22nd, 2020, for certain COVID-19 patients. We performed virtual screening studies of a proprietary compound library of >6000 molecules against conserved SARS-CoV-2 enzymes, namely papain-like protease (PLpro), 3C-like proteinase (3CLpro) e RNA-dependent RNA polymerase (RdRp). In these preliminary docking studies, we identified compounds with EC50 values in low micromolar range of concentration in cell viability assay in VeroE6 cells against SARS-CoV-2-mucIMB and SARS-CoV2-mucIMB-CB (alpha variant) strains. In particular, compound RS2523 inhibited SARS-CoV-2 PLpro with IC50= 27 μM and SARS-HCoV-OC43 strain with IC50= 4.30 μM. Compound RS2523 was selected as a lead compound for optimization studies. References [1] J. Osipiuk, SA. Azizi, S. Dvorkin, M. Endres, R. Jedrzejczak, K. A Jones, S. Kang, R. Youngchang Kim, V. G Lisnyak, S. L Maki, V. Nicolaescu, C. A Taylor, C. Tesar, Y. Zhang, Z. Zhou, G. Randall, K. Michalska, S. A Snyder, B. C Dickinson, A. Joachimiak, Nat Commun. 12 (2021) 743.
Discovery of new PLpro inhibitors against SARS-CoV-2 / Pecora, D.; Hucke, F.; Mastrangelo, E.; Milani, M.; Nalli, M.; La Regina, G.; Bugert, J. J.; Silvestri, R.. - (2021). (Intervento presentato al convegno Merck Young Chemists’ Symposium tenutosi a Rimini, Italia).
Discovery of new PLpro inhibitors against SARS-CoV-2
Pecora, D.;Nalli, M.;La Regina, G.;Silvestri, R.
2021
Abstract
There is an urgent need of effective drugs for the treatment of the SARS-CoV-2 infection. Remdesivir (Veklury®), a nucleotide analogue, is the only drug that was approved by FDA on October 22nd, 2020, for certain COVID-19 patients. We performed virtual screening studies of a proprietary compound library of >6000 molecules against conserved SARS-CoV-2 enzymes, namely papain-like protease (PLpro), 3C-like proteinase (3CLpro) e RNA-dependent RNA polymerase (RdRp). In these preliminary docking studies, we identified compounds with EC50 values in low micromolar range of concentration in cell viability assay in VeroE6 cells against SARS-CoV-2-mucIMB and SARS-CoV2-mucIMB-CB (alpha variant) strains. In particular, compound RS2523 inhibited SARS-CoV-2 PLpro with IC50= 27 μM and SARS-HCoV-OC43 strain with IC50= 4.30 μM. Compound RS2523 was selected as a lead compound for optimization studies. References [1] J. Osipiuk, SA. Azizi, S. Dvorkin, M. Endres, R. Jedrzejczak, K. A Jones, S. Kang, R. Youngchang Kim, V. G Lisnyak, S. L Maki, V. Nicolaescu, C. A Taylor, C. Tesar, Y. Zhang, Z. Zhou, G. Randall, K. Michalska, S. A Snyder, B. C Dickinson, A. Joachimiak, Nat Commun. 12 (2021) 743.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
