COVID-19: researchers identify molecules that can pave the way for new antiviral drugs

Researchers have discovered a series of molecules that expose COVID-19 to the body’s immune system, opening up the possibility for new antiviral drugs to treat the virus.

An international research team, led by Oxford Brookes University, has identified how the SARS-Cov-2 protein chemically modifies the virus’s genetic material – RNA – in order to ‘hide’ it from the human body’s natural immune system. This allows it to evade detection, replicate in human cells upon infection and then spread.

Small molecules can inhibit the protein enzyme NSP16

The researchers also identified a series of small molecules which are able to hinder the function of the NSP16 enzyme, therefore helping the human immune system to recognise the virus, and making it possible to create antiviral drugs to treat COVID-19.

Dr Victor Bolanos-Garcia, lead author of the paper and Senior Lecturer in Clinical Biochemistry at Oxford Brookes University said: “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.”

Developing new treatments

Limitations with current vaccines means it is essential to develop more effective treatments for COVID-19. Although several vaccine programmes are currently underway and have reached phase three, effective therapeutic options for the virus do not currently exist.

Professor Agatha Bastida from the Spanish National Research Council (CSIC) added: “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.”

The research team will now work to synthesise the new molecules and assess whether they are toxic to human cells.

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.



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