Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives

Andrea Citarella; Alessandro Dimasi; Davide Moi; Daniele Passarella; Angela Scala; Anna Piperno; Nicola Micale

doi:10.3390/biom13091339

Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives

Biomolecules. 2023 Sep 2;13(9):1339. doi: 10.3390/biom13091339.

Authors

Andrea Citarella¹, Alessandro Dimasi¹, Davide Moi², Daniele Passarella¹, Angela Scala³, Anna Piperno³, Nicola Micale³

Affiliations

¹ Department of Chemistry, University of Milan, Via Golgi 19, 20133 Milano, Italy.
² Department of Chemical and Geological Sciences, University of Cagliari, S.P. 8 CA, 09042 Cagliari, Italy.
³ Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, 98166 Messina, Italy.

Abstract

The main protease (M^pro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of M^pro produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 M^pro inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new M^pro inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.

Keywords: COVID-19; Paxlovid; SARS-CoV-2 Mpro; coronavirus; nirmatrelvir; peptidomimetics; protease inhibitors.

Publication types

Review

Grants and funding

FFABR_PA_MICALE_NICOLA_ATENEO_2022/University of Messina