Ebselen, Disulfiram, Carmofur, PX-12, Tideglusib, and Shikonin Are Nonspecific Promiscuous SARS-CoV-2 Main Protease Inhibitors.

ACS Pharmacology & Translational Science
Chunlong MaJun Wang


Among the drug targets being investigated for SARS-CoV-2, the viral main protease (Mpro) is one of the most extensively studied. Mpro is a cysteine protease that hydrolyzes the viral polyprotein at more than 11 sites. It is highly conserved and has a unique substrate preference for glutamine in the P1 position. Therefore, Mpro inhibitors are expected to have broad-spectrum antiviral activity and a high selectivity index. Structurally diverse compounds have been reported as Mpro inhibitors. In this study, we investigated the mechanism of action of six previously reported Mpro inhibitors, ebselen, disulfiram, tideglusib, carmofur, shikonin, and PX-12, using a consortium of techniques including FRET-based enzymatic assay, thermal shift assay, native mass spectrometry, cellular antiviral assays, and molecular dynamics simulations. Collectively, the results showed that the inhibition of Mpro by these six compounds is nonspecific and that the inhibition is abolished or greatly reduced with the addition of reducing reagent 1,4-dithiothreitol (DTT). Without DTT, these six compounds inhibit not only Mpro but also a panel of viral cysteine proteases including SARS-CoV-2 papain-like protease and 2Apro and 3Cpro from enterovirus A71 (EV-A7...Continue Reading


Jan 12, 2021·Expert Review of Clinical Pharmacology·Chiranjib ChakrabortyGovindasamy Agoramoorthy
Jan 25, 2021·Journal of Ethnopharmacology·Zhonglei Wang, Liyan Yang
Feb 12, 2021·ACS Infectious Diseases·Kas SteutenMatthew Bogyo
Feb 12, 2021·Proceedings of the National Academy of Sciences of the United States of America·Chunlong Ma, Jun Wang
Mar 20, 2021·Journal of Molecular Graphics & Modelling·Sheng GuoZhili Zuo
Apr 2, 2021·Archives of Toxicology·Cristina W NogueiraJoão B T Rocha
Apr 24, 2021·Journal of Medicinal Chemistry·Naoya KitamuraJun Wang
Apr 22, 2021·Advances and Applications in Bioinformatics and Chemistry : AABC·Bruno O VilloutreixPhilippe Beaune
May 22, 2021·Molecular Informatics·Pablo Andrei NogaraJoão Batista Teixeira Rocha
May 26, 2021·Nature Communications·Kangsa AmporndanaiS Samar Hasnain
Jun 1, 2021·Frontiers in Molecular Biosciences·Miao Mei, Xu Tan
Jun 12, 2021·SLAS Discovery·Kathryn M Nelson, Michael A Walters
Jun 19, 2021·Biomedit︠s︡inskai︠a︡ khimii︠a︡·A V SulimovV B Sulimov

❮ Previous
Next ❯

Datasets Mentioned


Methods Mentioned

enzymatic assay
thermal shift

Related Concepts

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Epigenetics Insights from Twin Studies

Find the latest research on epigenetics and twin studies here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.


Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.