1. Broad-spectrum antiviral drugs:
Tool for biosecurity
Jassi Pannu

2. BACTERIA VIRUSESFUNGHI PARASITES PRIONS

3. Why are viruses particularly concerning?
● Airbourne, droplet or contact transmission between
humans and/or animals
● Ability to harm hosts (virulence/pathogenicity)
● Small genomes, relatively easy to synthesize & manipulate,
potentially weaponize
● Lack of medical countermeasures

4. Narrow-
spectrum
antivirals
Broad-
spectrum
antivirals

5. “ Broad-spectrum therapeutics should be
pursued given their potential value,
even if the likelihood of identifying such
medicines remains low. ”
Source: Pandemic Pathogens. Johns Hopkins Center for Health Security

6. The promise of broad-spectrum antivirals
● Treat entirely new or engineered virus
● Treat before detailed diagnosis
● More cost-effective to develop versus “one bug-one drug”
approach
● Treat only those infected, versus vaccinating all
● Efficient stockpiling in case of catastrophic event or attack

7. Main Roadblocks
to Development
Scientific
Commercial
Regulatory

8. Scientific
Target shared mRNA
secondary structures or
shared host targets
Repurpose existing
host-targeting drugs (e.g.
kinase inhibitors, chloroquine,
nitazoxanide)
Boost existing immune system
function (e.g. novel
interferons)
Viruses are genetically and
mechanistically divergent

9. Scientific
Viruses are genetically and
mechanistically divergent
Target shared mRNA
secondary structures or
shared packaging mechanisms
Repurpose existing
host-targeting drugs (e.g.
kinase inhibitors)
Boost immune system
function (novel interferons)

10. NIH-funded labs working on BSAVs
Over $250M provided to fund this research:
Paul Malone Allen Washington University
- $32.7M, 2014-2018
Autophagy modulators as novel broad-spectrum
anti-infective agents
Jeffrey Glen Stanford University
- $28.6M, 2014-2019
Advancing broad spectrum host-targeting antiviral
strategies to the clinic
Ulrich H Von Andrian Harvard Medical School
- $9.751 M, 2014-2018
Mechanisms and immunological consequences of host-virus
interactions
Ralph Baric UNC Chapel Hill
- $3.79M, 2017-2019
Broad-spectrum antiviral GS-5734 to treat MERS-COV and
related emerging COV
Anne Moscona Columbia University
- $3.7M, 2015-2019
Engineering protease-resistant alpha-beta peptides for
broad spectrum antivirals
Beth C Levine (2) UT Southwestern
- $2.0M, 2018
Autophagy-inducing peptides and target identification for
treatment of viruses
UT Southwestern
- $1.5M, 2019
RP1: Targeting Beclin 1 complexes for broad-spectrum
anti-infective therapeutics
John Huibregtse UT Austin
- $3.1M, 2011-2019
Mechanism and function of ISG15
Herbert W Virgin (2) Washington University
- $1.6M, 2018
Genes/pathways for ATG gene-dependent inhibition of
viruses & parasite infection

11. Commercial
Little incentive to develop drugs
for rare events in advance
Low reimbursement for
anti-infective drugs by
government and insurance payers
in absence of active epidemic
Options market to distribute risk
from pharmaceutical companies to
more risk-tolerant investors
Subscription model that provides
health systems with access to latest
antivirals after paying upfront

12. Commercial
Advance market commitments from
non-market actors such as
governments, NGOs, philanthropists
Little incentive to develop drugs
for rare events in advance
Low reimbursement for
anti-infective drugs by
government and insurance payers
in absence of active epidemic

13. Regulatory
New approval pathways for
broad-spectrum drugs
Increase patent length for antivirals
to incentivize development
Lobby for greater flexibility in
BARDA funding
Lobby for government “pull”
mechanisms, i.e. rewards to
companies for developing certain
drugs
FDA drug approval process for
broad-spectrum drugs
The Biological Advanced Research
and Development Authority is reliant
on Congressional vote for certain
types of funding

14. BARDA, detail
● BARDA (2006) is the “biological DARPA”
Source: BARDA FY 2017

15. Regulatory
New approval pathways for
broad-spectrum drugs
Government patent buyouts
Lobby for greater flexibility and
consistency in BARDA funding
Global prioritization of epidemic
preparedness R&D
FDA drug approval process for
broad-spectrum drugs
The Biological Advanced Research
and Development Authority is reliant
on Congressional vote for certain
types of funding