Broad spectrum antivirals shift the drug model paradigm
by Jeannie Wraight
The recent spread of emerging pandemic viruses such as Zika and Ebola has increased the urgency for the discovery and development of new antiviral agents. In the past, drug development has utilized the one drug-one pathogen model where for every virus a specific drug or drugs were developed. Researchers are now looking at a new model of drug development where drugs called broad spectrum antivirals (BSA) could be used to treat numerous viruses.
BSAs are an issue that I touched on in a previous edition of Destination: Cure called One Drug, Many Possibilities [A&U, December 2015], which focused on one specific BSA, AR-12.
In this two-part series, we’ll take a deeper look at BSAs and their broader application. In next month’s Part II, we’ll explore how BSAs work. But first let’s look at why they’re important.
BSAs are drugs that can be used for the treatment of several different viruses at once. Unlike current ARVs that are designed specifically to work against one virus such as HIV or hepatitis C by targeting steps of the viral replication process, BSAs utilize common cellular factors and pathways that numerous viruses use. This would allow them to prevent viruses from taking hold, with little to no risk of the development of drug resistance.
In addition to a higher barrier to drug resistance, BSAs would be beneficial in numerous ways. BSAs could be kept on hand, particularly in areas where viral outbreaks are more likely to occur, and quickly administered for fast, effective treatment of a wide range of viruses and genotypes. Early treatment would reduce the occurrence of viral transmission from one person to another, and could prevent a widespread outbreak from occurring. BSAs would also reduce the complexity of antiviral regimens where drug-drug interactions can occur.
History is fraught with viral outbreaks that led to epidemics/pandemics that claimed the lives of hundreds of millions of people. Whether new pandemics will occur has never been in question: It’s simply a matter of when and how severe.
In 1918–1919, an especially virulent strain of influenza caused a catastrophic loss of life across the globe. Approximately 500 million people were infected with this strain of flu, most commonly known as the “Spanish Flu.” Estimates of the number of deaths range from 50–100 million individuals or three to five percent of the world’s population. Two of my great-grandparents were among those who died.
The bubonic plague, or the “Black Death,” occurred from 1347 to 1351, killing at least 75 million of the world’s population of 450 million.
Less deadly but more recent pandemic viruses include the H1N1 flu which claimed between 151,700 and 575,400 lives worldwide and 12,469 deaths in the U.S. between April 2009 and April 2010; a virus identified in the Far East killed approximately 69,800 people in the United States from September 1957 to March 1958 and the Ebola virus which caused the deaths of 11,316 people. HIV/AIDS has been responsible for the deaths of 35 million individuals since the beginning of the pandemic. Each year approximately 55,000 people in the United States die of the flu.
Most recently, the Zika virus has generated fear throughout 70 countries and territories. Although no one who has been infected with Zika has died, the virus is strongly linked to microcephaly, which causes severe birth defects. As of this week in the U.S., 580 pregnant women have been diagnosed with Zika with a total of sixteen total liveborn infants with birth defects and five pregnancy losses with birth defects.
With each viral outbreak, new funding must be found to research and develop treatments and vaccines. In 2009, Congress approved $1.85 billion to combat influenza, in 2014, $5.4 billion was provided to stop Ebola, and President Obama requested $1.9 billion dollars from Congress to combat Zika, the large majority of which has yet to be approved. In such cases, funding is taken from other initiatives.
New viral outbreaks can have a severe effect on other priorities such as HIV. A report by the United Nations Development Programme (UNDP) Global Fund Partnership team, found the Ebola epidemic in Sierra Leone had virtually halted national HIV efforts with many people having to stop their ARVs due to problems in the supply chain, caused by a redirection of resources such as transportation and manpower.
New and emerging pandemics are consistently on the horizon. There is little ammunition to combat these viral outbreaks and prevent viruses from turning into epidemics or pandemics.
The development and availability of broad spectrum antivirals, would allow us to quickly save lives and prevent new or reoccurring outbreaks from becoming deadly epidemics or pandemics such as those described above.
In next month’s column, we’ll take a deeper look at how BSAs work and explore the moral aspects of the political and pharmaceutical support of this new class of drugs.
Jeannie Wraight is the former editor-in-chief and co-founder of HIV and HCV Haven (www.hivhaven.com) and a blogger and writer for TheBody.com. She is a member of the Board of Directors of Health People, a community-based organization in the South Bronx and an advisor to TRW (Teach me to Read and Write), a community-based organization in Kampala, Uganda. She lives with her husband in New York City.