A review of the current landscape of SARS-CoV-2 main protease inhibitors: Have we hit the bullseye yet?

Identificador:  imarina:9242334

Handle: https://hdl.handle.net/20.500.11797/imarina9242334

Autors:  Macip, G; Garcia-Segura, P; Mestres-Truyol, J; Saldivar-Espinoza, B; Pujadas, G; Garcia-Vallvé, S

Resum:
In this review, we collected 1765 severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) M-pro inhibitors from the bibliography and other sources, such as the COVID Moonshot project and the ChEMBL database. This set of inhibitors includes only those compounds whose in-hibitory capacity, mainly expressed as the half-maximal inhibitory concentration (IC50) value, against M-pro from SARS-CoV-2 has been determined. Several covalent warheads are used to treat covalent and non-covalent inhibitors separately. Chemical space, the variation of the IC50 inhibitory activity when measured by different methods or laboratories, and the influence of 1,4-dithiothreitol (DTT) are discussed. When available, we have collected the values of inhibition of viral replication measured with a cellular antiviral assay and expressed as half maximal effective concentration (EC50) values, and their possible relationship to inhibitory potency against M-pro is analyzed. Finally, the most potent covalent and non-covalent inhibitors that simultaneously inhibit the SARS- CoV-2 M-pro and the virus replication in vitro are discussed. © 2021 by the authors. Li-censee MDPI, Basel, Switzerland.