biostudies-literatureAgost-Beltran LJaume I University2523https://www.ebi.ac.uk/biostudies/studies/S-EPMC9026863biostudies-literatureUnknown27(8)Since the outbreak of COVID-19, one of the strategies used to search for new drugs has been to find inhibitors of the main protease (Mpro) of the virus SARS-CoV-2. Initially, previously reported inhibitors of related proteases such as the main proteases of SARS-CoV and MERS-CoV were tested. A huge effort was then carried out by the scientific community to design, synthesize and test new small molecules acting as inactivators of SARS-CoV-2 Mpro. From the chemical structure view, these compounds can be classified into two main groups: one corresponds to modified peptides displaying an adequate sequence for high affinity and a reactive warhead; and the second is a diverse group including chemical compounds that do not have a peptide framework. Although a drug including a SARS-CoV-2 main proteMolecules (Basel, Switzerland)Advances in the Development of SARS-CoV-2 Mpro Inhibitors.PMC9026863(UJI-2021-71); SomUJIContraCovid (crowdfunding campaign)Fernandez-de-la-Pradilla AAgost-Beltran LGonzalez FVRodriguez Sde la Hoz-Rodriguez SBou-Iserte LfalseAdvances in the Development of SARS-CoV-2 Mpro Inhibitors.Since the outbreak of COVID-19, one of the strategies used to search for new drugs has been to find inhibitors of the main protease (Mpro) of the virus SARS-CoV-2. Initially, previously reported inhibitors of related proteases such as the main proteases of SARS-CoV and MERS-CoV were tested. A huge effort was then carried out by the scientific community to design, synthesize and test new small molecules acting as inactivators of SARS-CoV-2 Mpro. From the chemical structure view, these compounds can be classified into two main groups: one corresponds to modified peptides displaying an adequate sequence for high affinity and a reactive warhead; and the second is a diverse group including chemical compounds that do not have a peptide framework. Although a drug including a SARS-CoV-2 main prote2022-01-01T00:00:00Z2022 Apr2025-04-20T00:18:33.732Z2025-02-19T01:53:45.811ZS-EPMC90268633545872110.3390/molecules27082523