Two anti-inflammatory drugs found that inhibit the replication of the COVID-19 virus

May 27, 2020

Since the outbreak of the COVID-19 pandemic and its rapid spread, the scientific community has been working on developing an effective treatment for the virus responsible for the disease. Finding drugs that can inhibit the infection caused by SARS-CoV-2 is an essential step to finding the vaccine that can definitively bring the spread of the virus to an end. In this regard, the URV's Cheminformatics and Nutrition research group has carried out a computational screening to predict whether there is a medicine authorised for treating another pathology that can inhibit the main protease of the virus (M-pro). This is key to the whole process because this enzyme plays an essential role in the replication of the virus.

The study demonstrates that a human and a veterinary anti-inflammatory drug - Carprofen and Celecoxib - inhibit a key enzyme in the replication and transcription of the virus responsible for COVID-19. The aim of the study was to use computer techniques to analyze whether 6,466 drugs authorized by various drug agencies for both human and veterinary use could be used to inhibit the M-pro enzyme. This enzyme is a protease that is responsible for cutting two polypeptides (generated by the virus itself) and generating a number of proteins that are essential for the reproduction of the virus. Some of the trials coordinated by the WHO against the COVID-19 pandemic also aim to inhibit M-pro using two antiretrovirals such as Lopinavir and Ritonavir (drugs initially designed to treat HIV).

As a result of the study conducted at the URV, it has been predicted that 7 of these 6,466 drugs may inhibit M-pro. The results have been shared with the international initiative COVID Moonshot which has selected 2 of these 7 compounds (i.e., Carprofen and Celecoxib) in order to test their ability to inhibit M-pro in vitro. The results obtained show that at a concentration of 50 μM of Celecoxib or Carprofen, the inhibition of the in vitro activity of M-pro is 11.90 and 4.0%, respectively. Therefore, both molecules could be used as a starting point for further lead optimization to obtain even more potent derivatives.

The study by the Cheminformatics and Nutrition research group from the Biochemistry and Biotechnology Department of the URV has been led by Drs. Gerard Pujadas and Santi Garcia-Vallvé with the collaboration of Drs. Aleix Gimeno, María José Ojeda-Montes and Adrià Cereto-Massagué, the PhD students Guillem Macip and Bryan Saldivar-Espinoza and student Júlia Mestres-Truyol (double degree student in Biotechnology and in Biochemistry and Molecular Biology at the URV). It has been published by the International Journal of Molecular Sciences (IJMS) and is the first to be published worldwide on drug repositioning as inhibitors of SARS-CoV-2 M-pro where computational predictions are experimentally corroborated. The remaining 5 molecules are expected to be selected soon by COVID Moonshot so that their bioactivity can be tested as well.
Reference: Gimeno, A.; Mestres-Truyol, J.; Ojeda-Montes, M.J.; Macip, G.; Saldivar-Espinoza, B.; Cereto-Massagué, A.; Pujadas, G.; Garcia-Vallvé, S. "Prediction of Novel Inhibitors of the Main Protease (M-pro) of SARS-CoV-2 through Consensus Docking and Drug Reposition". Int. J. Mol. Sci. 2020, 21, 3793.

Universitat Rovira i Virgili

Related Transcription Articles from Brightsurf:

Circular RNA regulates neuronal differentiation by scaffolding an inhibitory transcription complex
In a screening for a functional impact to the neuronal differentiation process, Danish researchers identified a specific circular RNA, circZNF827, which surprisingly 'taps the brake' on neurogenesis.

Transcription factors may inadvertently lock in DNA mistakes
A team of Duke researchers has found that transcription factors have a tendency to bind strongly to ''mismatched'' sections of DNA, i.e. sections of the genome that were not copied correctly.

New role assigned to a human protein in transcription and genome stability
DNA-RNA hybrids, or R loops, are structures that generate genomic instability, a common feature of tumor cells.

CeMM study reveals how a master regulator of gene transcription operates
Using TPD technology, CeMM researchers set out to understand set out to understand the primary role of a key regulator of transcription, the human Mediator complex.

Researchers find new role for dopamine in gene transcription and cell proliferation
A joint group of researchers at the George Washington University and the University of Pittsburgh have found that dopamine and the dopamine D2 receptor modulate expression via the Wnt/β-catenin signaling pathway.

SMAD2 and SMAD3, two almost identical transcription factors but with distinct roles
Both transcription factors regulate the expression of genes involved in embryo development, among other functions, although they exert very different roles.

Study explores role of mediator protein complex in transcription and gene expression
A new study led by Ryerson University called 'The Med31 Conserved Component of the Divergent Mediator Complex in Tetrahymena thermophila Participates in Developmental Regulation' advances existing knowledge about transcription and gene expression.

New members found in a transcription factor complex that maintains beta cells
A protein complex in the nucleus of beta cells contains different proteins that work together to regulate genes important for the development and maintenance of functional beta cells.

Testifying while black: A linguistic analysis of disparities in court transcription
A new study has found that court reporters transcribe speakers of African American English significantly below their required level of accuracy.

HKUST scientists discover how RNA PoII maintains accurate transcription with super computer
Scientists from the Hong Kong University of Science and Technology have recently uncovered the mechanisms of how RNA polymerase II performs intrinsic cleavage reaction to proofread RNA transcriptions, shedding light on how misregulation of accurate transcription can lead to diseases including cancer and Alzheimer's disease.

Read More: Transcription News and Transcription Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to