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Repurposing Combinations of Approved Drugs for Broad-Spectrum Antiviral Protection Against Global Biothreats

Viruses are cleverly dangerous; they jump from species to species, mutate to evade vaccines, and cause a plethora of human diseases and deaths each year. Vaccine and antiviral drug makers can barely keep pace with global demand, and efforts can be stymied by low projected profits, especially for drug use in resource-limited countries. The word “outbreak” brings to mind viruses such as SARS, Ebola and Lassa. Although highly curative and suppressive therapies are available for hepatitis C and HIV, such is not the case for many viruses (including the above) that regularly threaten humanity on a global scale. We aim to develop a new antiviral drug cocktail, a mixture of currently approved drugs that in combination exerts synergistic and broader protection from a wider range of viruses (i.e., broad-spectrum) than currently possible when each drug is used separately. Such a practical anti-viral would be extremely valuable, especially in the initial stages of an outbreak before viral genome sequences are available and viral-specific counter-measures, if available, can be deployed, particularly to resource-, geographic-, or societally-challenged locales. The project derives from recent novel findings made by our multi-institutional team showing that: i) approved drugs developed for other clinical indications inhibit entry of diverse, globally threatening viruses and ii) combining approved drugs in two- or three-drug combinations provides synergistic suppression of many viruses, mainly by blocking virus entry. We hypothesize that repurposing combinations of orally-available approved drugs that target discrete steps in virus entry provides effective and easily deliverable suppression of globally prevalent viruses that endanger humanity. Our goal is to develop in vivo-active and clinically safe combinations of approved drugs that confer protection against Orthomyxo-, Filo-, and Arena-viruses. If successful, our approach will be paradigm shifting because it i) obviates the massive costs required for traditional antiviral drug development (i.e., a single drug for a single virus), ii) should be applicable to many other medically significant viruses that share a similar route of entry into cells, iii) will permit affordable room-temperature stockpiling of drugs that can be administered in single oral doses to enhance readiness for the next virus outbreak, and iv) will provide affordable and practical countermeasures for viral infections in resource-limited countries, where antiviral drug development is often minimal due to perceived low patient numbers and profits.

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