A PHARMACOLOGICAL FRAMEWORK FOR INTEGRATING TREATING THE HOST,
REPUPOSING AND THE DAMAGE RESPONSE FRAMEWORK IN COVID19 DISEASE
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.