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A PHARMACOLOGICAL FRAMEWORK FOR INTEGRATING TREATING THE HOST, REPUPOSING AND THE DAMAGE RESPONSE FRAMEWORK IN COVID19 DISEASE
  • Richard Head,
  • Jennifer Martin
Richard Head
University of South Australia
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Jennifer Martin
The University of Newcastle
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Abstract

Historically in a pandemic the focus has been upon identifying agents that would eliminate the invading species with as little damage as possible to the host. Recently discussion has moved, particularly with COVID-19, from antiviral therapy to delineating the treatment of the host from treatment. With the latter, the approach brings together three concepts; treating the host, the damage response framework and therapeutic repurposing. The integration of these three areas play heavily to the traditional strength of pharmaceuticals in providing a period of stabilization prior to the introduction of subsequent interventions to permit time for the development of novel anti-viral drugs and vaccines . In integrating approaches to repurposing, host treatment and damage response we identified three key properties that a potentially effective repurposed drug must posses by way of a framework. There must be homology with the pathogenesis of the disease, ideally targeted to the conserved pathophysiological outcomes of the vial attack, have a defined locus within the spectrum from prevention to severe disease and finally draw upon the historical dose and safety experience of the repurposed drug. By way of illustration we have mapped therapeutic agents that impact upon the renin angiotensin system using this approach. Collectively this type of analysis reveals the importance of existing data (repurposed information and administrative observational data) and the details of the known pathophysiology of the viral attack are in approaches to treating the host; and with COVID-19 the significance of a pre-existing RAS-mediated inflammatory disposition.