Inhibitors of SARS-CoV-2 main protease: Biological efficacy and toxicity aspects

Jana Viskupicova; Petronela Rezbarikova; Lucia Kovacikova; Helena Kandarova; Magdalena Majekova

doi:10.1016/j.tiv.2023.105640

Inhibitors of SARS-CoV-2 main protease: Biological efficacy and toxicity aspects

Toxicol In Vitro. 2023 Oct:92:105640. doi: 10.1016/j.tiv.2023.105640. Epub 2023 Jul 5.

Authors

Jana Viskupicova¹, Petronela Rezbarikova¹, Lucia Kovacikova², Helena Kandarova³, Magdalena Majekova⁴

Affiliations

¹ Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia.
² Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia; Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia.
³ Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia; Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovakia.
⁴ Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia. Electronic address: magdalena.majekova@savba.sk.

PMID: 37419426
DOI: 10.1016/j.tiv.2023.105640

Abstract

The emergence of the highly contagious respiratory disease, COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a significant global public health concern. To combat this virus, researchers have focused on developing antiviral strategies that target specific viral components, such as the main protease (M^pro), which plays a crucial role in SARS-CoV-2 replication. While many compounds have been identified as potent inhibitors of M^pro, only a few have been translated into clinical use due to the potential risk-benefit trade-offs. Development of systemic inflammatory response and bacterial co-infection in patients belong to severe, frequent complications of COVID-19. In this context, we analysed available data on the anti-inflammatory and antibacterial activities of the SARS-CoV-2 M^pro inhibitors for possible implementation in the treatment of complicated and long COVID-19 cases. Synthetic feasibility and ADME properties were calculated and included for better characterisation of the compounds' predicted toxicity. Analysis of the collected data resulted in several clusters pointing to the most prospective compounds for further study and design. The complete tables with collected data are attached in Supplementary material for use by other researchers.

Keywords: ADMET; Anti-inflammatory; Antibacterial; COVID-19; M(pro) inhibitors; Specific; toxicity..

MeSH terms

Antiviral Agents / pharmacology
COVID-19*
Humans
Molecular Docking Simulation
Post-Acute COVID-19 Syndrome
Prospective Studies
SARS-CoV-2

Substances

3C-like proteinase, SARS-CoV-2
Antiviral Agents