Development and Advancement of Broad-Spectrum Respiratory Antivirals
Abstract
This Focused Program Award application is directed towards the Development and Advancement of Broadspectrum Respiratory Antivirals (DABRA) and relates to the Fiscal Year 2019 Peer Reviewed Medical Research Program topic area of “Respiratory Health,” under the area of encouragement “treatment of respiratory symptoms and ailments possibly associated with deployed and redeployed military personnel.” Specifically, during 2005-2006 in Iraq and Afghanistan, deployed military experienced wartime respiratory illness rates of ~15% per month; and overall rates were estimated at ~40%. Military personnel performance was affected in 34% of respiratory illness cases. These infections can significantly impact training and readiness, accounting for 12,000 to 27,000 days of lost preparation time each year. Respiratory infections also represent the most commonly diagnosed medical condition among military recruits and advanced trainees. Problem: While respiratory infections caused by bacteria are relatively simple to treat due to the availability of broad-spectrum antibiotics that are effective against multiple bacterial species, similar treatment of viral infections is more difficult. Vaccinations, which could limit viral induced respiratory infections, are not available for many respiratory viruses of military relevance, such as coronaviruses, human rhinoviruses, and respiratory syncytial virus. The influenza yearly vaccine effectiveness varies, depending on how well matched it is to the circulating strains, and the vaccine given by the military for adenovirus does not protect against all strains. In addition, antiviral therapeutics do not exist for most respiratory agents. Even when antivirals are available, they require time-consuming laboratory diagnosis before treatment can begin, which can be a barrier in deployed military settings where such point-of-care diagnostics might not be available. Since influenza antivirals are most efficient when given in a 48-72 hour window, a delay in diagnosis can mean a less effective outcome, increasing likelihood of secondary infections, and spread throughout closely housed military quarters. In addition, of the few available antivirals, including the three approved for influenza, all function by targeting virus specific proteins. The high mutation rate of these viruses makes the emergence of resistance to these drugs a matter of time. Thus, a new strategy to develop antivirals that exhibit activity against multiple respiratory viruses is necessary. These would be broad-spectrum therapies that can be given without the need for diagnosis, are less susceptible to the development of viral resistance, and do not require specialized storage conditions and or administration by medical experts, and would significantly impact military readiness through enhancing durable treatment options that obviate the requirement for diagnostics prior to treatment. This will enable rapid administration to more effectively treat infections, prevent viral spread, and limit associated secondary infections, especially in environments where advance medical infrastructure is not available. Solution: To tackle the overarching challenge of developing broad-spectrum respiratory antivirals, we hypothesize that a novel therapeutic strategy that involves the development of drugs that target host (human) proteins, rather than current therapeutic strategies that target viral proteins, will be required. This will be necessary because respiratory viruses, unlike bacteria, do not encode common targets. However, recent findings by us and other groups have demonstrated that their replication can be modulated by similar host (human)-encoded pathways. Thus, we propose to pursue two complementary host-directed strategies. The first is focused on advancing broad-spectrum antiviral assets that target host (human) cellular factors required for replication of multiple respiratory virus families. While the second is focus
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010270
Entities
People
- Sumit K Chanda
Organizations
- Sanford Burnham Prebys Medical Discovery Institute
- United States Army