HIV and Drug Discovery
Having grown
up and experienced the worst HIV epidemic in the early 1990, it was a
childhood goal to contribute to the discovery of life saving drugs in
memory of the many innocent lives that succumbed to this pandemic
whilst adding a contribution on behalf of our generation to this
chronic global health problem. HIV is still at large and by any means
is our generational problem more so the millennials that lack
first-hand experience of this notorious killer. The only validated
weapon are drugs called anti-retroviral therapy whose continuous race
to override a exceedingly cunning “super bug-HIV” rests upon
dedicated unsung heroes (Drug
discoverers)
that spend many sleepless nights and long working days for the good
of many. My own personal experiences led to the conjecturing of the
“science
for social impact phenomenon”
to recapitulate these sacrifices and for the public to understand
based on facts and evidence while possibly garnering more support for
such revolutionary acts. Thus “Science
for Social Impact”
equals “Revolutionary
Science”.
This work was done at the Burnet Institute in HIV following upon my
discovery expertise accumulated during my PhD at La Trobe University.
We to discover the next generation drugs against HIV and the
presentation replicates my landmark presentation at the Australian
Virology Society in December 2017. I made it that, I am originally
from Uganda, one of the countries worst by the epidemic. At a time it
was just 4 days ago from World AIDS day which reminded us what we
have to do and why we should care. Current statistics stated that HIV
is still at large and it kills 2 people per minute and 3 new
infections recorded in the same time frame. The big question is what
really changed the once death sentence to a chronic manageable
illness? These were the antiretroviral drugs which target critical
HIV life cycle targets. The main ones target reverse transcriptase,
an enzyme critical for HIV virus replication. These form the major
backbone HIV treatment and prevention through pre-exposure
prophylaxis. They are only two classes; The nucleoside/nucleotide RT
active site inhibitors and the non-nucleoside reverse transcriptase
inhibitors that target an allosteric site. Considering their
extensive benefits, global efforts have been directed towards HIV
elimination HIV by 2030, a plan underpinned by a massive global
scale-up of antiretroviral therapy for both HIV treatment and
prevention, a phenomenon similar to mass drug administration. Drug
resistance, toxicity and an eventual exhaustion of drug options is a
big threat to our eradication campaigns as we have deployed all our
drug arsenal against a moving target HIV. This is a tipping point as
HIV might outrun our response, keeping our patients lingering on the
verge of death. Therefore, superior and timely tools are required to
tide of war.
In response,
we have employed a new paradigm in drug discovery called
Fragment-based drug design (FBDD) to develop novel drug classes
targeting reverse transcriptase a well validated target at
distinctive conserved novel allosteric sites. This is to date the
best approach for the job to churn out cheap, and novel drug classes
compared to other approaches. It works by building drugs from small
chemical units called fragments, that bind intimately bind our target
efficiently. These small fragments can be expanded without
compromising the original binding fragment profile. To this end,
using a combination of biophysical binding and biochemical RT
inhibitory assays we identified 3 inhibitory fragments that are
active against circulating WT and resistant HIV strains. These hit
sites distinctive allosteric sites, with modes of action distinctive
to available drugs, thereby underpinning our drug discovery program.
With this we can fragment-out HIV once and for all.
Author:
Dr. George Williams Mbogo
CEO BioTranslate International
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