Scientific analysis of a protein enzyme found in COVID-19 could lead to the development of new drugs to treat the virus, research led by Oxford Brookes University scientists has found.
An international research team has identified how the SARS-Cov-2 protein NSP16 chemically modifies the virus genetic material - RNA - in order to ‘hide’ it from the human body's natural immune system. By evading detection with this ‘trojan horse’ feature, the virus is able to replicate in human cells upon infection and spread.
The researchers also identified a series of small molecules which are able to inhibit the function of the NSP16 enzyme, which means it is possible to create antiviral drugs to treat COVID-19.
Small molecules can help immune system recognize virus
Although several vaccine programmes are currently underway, including the recently announced Pfizer-BioNTech where preliminary data suggest a 90% efficacy, and some drugs have been repurposed to aid the treatment of COVID-19, effective drug therapies to treat the virus do not currently exist. Many viral diseases are treated with antiviral drugs. Therefore, expanding the repertoire of therapeutic drugs to treat COVID-19 is important and timely.
Through the integration of computational chemistry methods and protein structure-based drug design with molecular dynamics and pharmacology approaches, the team has identified a series of small molecules which are able to inhibit the function of the NSP16 enzyme.
Stopping the NSP16 enzyme from functioning leaves the virus RNA exposed to recognition by the human immune system, which severely limits the replication of the SARS-CoV-2 virus in infected cells.
The small molecules we have identified as inhibitors of NSP16 show promising pharmacological properties. They provide a solid scientific base to develop novel inhibitors of NSP16 to treat COVID-19.”
Dr Victor Bolanos-Garcia, Lead author of the paper, Senior Lecturer in Clinical Biochemistry, Oxford Brookes University
Urgency to develop more effective treatments for COVID-19
Limitations with current vaccines means developing alternative therapies to treat COVID19 remains crucial. The research team will now work to synthesise the new molecules and assess whether they are toxic to human cells.
So far, Remdesivir and Favipiravir are the most promising antiviral drugs against SARS-CoV-2 tested in clinical trials. However, a recent study on SARS-CoV-2 found mutations in different genes of this virus that showed resistance to these antiviral drugs. These findings demonstrate the urgency to develop more effective antivirals to treat COVID-19.”
Agatha Bastida, Professor , Spanish National Research Council (CSIC)
The research was conducted by researchers at Oxford Brookes University, the Institute of Medical Chemistry, University of Saint Francis Xavier and the Spanish National Research Council.
The research paper is published in the journal Catalysts
Morales, P., et al. (2020) Interfering with mRNA Methylation by the 2′O-Methyltransferase (NSP16) from SARS-CoV-2 to Tackle the COVID-19 Disease. Catalysts. doi.org/10.3390/catal10091023.