Authors: John Nemunaitis (Gradalis, TX USA)
Take a look behind the scenes of a recent Future Virology paper, titled ‘Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection: Let the virus be its own demise’ as John Nemunaitis (Gradalis, TX, USA) discusses the role of the furin enzyme, the potential repurposing of a cancer immunotherapy treatment and the future of this field.
What inspired you to write this piece?
A national concern that there is a need for therapeutic approaches against SARS-CoV-2.
How does SARS-COV-2 rely on the furin enzyme and what makes it an attractive therapeutic target?
The genetic alteration that enabled SARS-CoV-2 to infect humans included a functional furin cleavage sequence that is needed for viral entry, protein assembly and propagation. By targeting a highly conserved host cell protein (furin), not only are viral dynamics effected, but resistance due to viral mutation is eliminated.
How does GM-CSF help to mount antiviral response?
GM-CSF expands the efficacious opportunity to include immune response activation against SARS-CoV-2 and facilitates the generation of personal antibodies against relevant SARS-CoV-2 antigens that are unique to that patient.
What is the basis behind repurposing the dual Vigil plasmid to tackle SARS-CoV-2?
This hypothetically provides both a therapeutic effect against furin activation and a vaccine effect of durable immune protection, leading to personal generation of neutralizing SARS-CoV-2 antibodies. Vigil plasmid is also used clinically in experimental treatment of ovarian cancer and Ewing’s sarcoma. No significant drug-related toxic effect has been observed, and benefit with respect to improved relapse-free survival and overall survival has been suggested in clinical trial.
What is the potential of using aerosolized therapeutics for administering such a plasmid?
Highly likely. We have already constructed lyophilized particles of optimal design, which have shown functional activity. We are now working with several teams of scientists to optimize inhaler dosing and use.
What are your predictions for the next 10–15 years in this field? What do you hope to see?
Antiviral therapeutic approaches that block viral dependent host signals will be critical in combination with immune response-generating vaccines because the mutational capability of this class of virus will likely limit traditional vaccine effectiveness and global activity. Expansion of dual activity therapeutics will increase in use over the next 10–15 years and will likely involve use against multiple viral pathogens.
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