Beyond One Bug, One Drug
Broad spectrum antivirals shift the drug model paradigm, part II
by Jeannie Wraight
In the October issue of A&U, Destination: Cure explored what broad spectrum antivirals (BSA) are, why they are an important type of drug and how BSAs could be used to fight existing and emerging viruses and epidemics. In this month’s edition, we’ll look at how BSAs work and how they are not only a medical and scientific issue, but a political and ethical issue as well.
BSAs will most likely be designed for short-term use because the level of toxicity may be too high for continual use. This may not make them optimal for the treatment of HIV but could be highly beneficial when treating viruses such as Dengue fever, Zika, Ebola, SARS, MER, and Chickamauga, among others, as well as new viral outbreaks.
However, people with HIV may specifically benefit from BSAs. In addition to resource distribution as discussed in Part I, it is largely unknown if HIV-positive people with low CD4 counts are at a greater risk from additional viruses across the board. That is, whether HIV infection places an individual at a higher risk for contracting other viruses and/or experiencing more severe complications seems to be virus-specific.
According to the CDC, it does not appear that people living with HIV have a greater risk of contracting Zika, or thus far have been seen to experience greater symptoms. However, of the known cases of Zika in HIV-positive people, all three individuals were successfully virally suppressed. It is yet unknown whether this would be true in those who are severely immune-compromised, as seen in Dengue fever where those with suppressed viruses and high CD4 counts did not experience a greater degree of symptoms but those with low CD4 counts did.
The goal of an antiviral is to prevent a virus from entering a cell and reproducing more copies of itself. Traditional antiviral drugs, such as those taken against HIV, attempt to stop an invading virus during various stages of this process. These include halting the infiltration of the target cell by preventing the virus from binding to the cellular receptor; targeting the processes that synthesize virus components such as reverse transcription or integrase; and inhibiting assembly or preventing budding, to name a few.
One problem with the approach of targeting these viral proteins is that if a virus mutates, an antiviral can become ineffective. Broad spectrum antivirals differ from traditional antivirals because, instead of viral proteins, they target cellular components that the virus hijacks in order to reproduce. By doing so, the virus is unable to overcome the drug through mutation.
However, one major problem with this approach is finding a cellular component that the virus uses but won’t compromise the cell if shut down. In other words, finding a function that can be hindered for long enough to kill off the virus without doing harm to the person carrying the virus.
Politically, the support of the development of the field of BSAs should be an ethical necessity. Exploring this class of drugs in order to potentially have a drug on hand to quickly treat small viral outbreaks before they reach epidemic status is a no-brainer. Whereas the pursuit of vaccines and the design and implementation of effective procedures to prevent viruses from spreading are essential, so should be our commitment to those already infected, a response we did not see in the early days of the AIDS crisis.
As stated in a 2015 abstract published in the Frontiers of Microbiology, “The emerging SARS, H1N1, and MERS, as well as re-emerging WEE/EEE and EBOVes are lethal and transmissible through travelers. They have been identified as high priority biodefense pathogens by the United States. The high virulence of these viruses and the absence of effective therapies have posed an ongoing threat to the public health. The conventional one-bug-one-drug paradigm is insufficient to address the challenge of emerging and re-emerging viral pathogens, and few drugs are currently available to a prompt control of epidemic viral diseases. Thus, it is imperative to develop a broad-spectrum class of antiviral agents….”
In order to create the paradigm shift needed to deviate from the “one-bug-one- drug” model of viral drug development, the pharmaceutical industry (in addition to the government) must commit to challenging the profit-over-lives, business-as-usual attitude that generates hundreds of billions of dollars. In doing this, they risk the high profits that would be obtained through one or numerous drugs to treat each virus.
At present almost all research and drug development of BSAs is performed and supported by academic institutions, the NIH, and a few small biotech companies. Pharmaceutical giants with the resources to support the expensive endeavor of developing new BSAs need to step in the ring and initiate research and/or take early stage BSAs, already in development, through the process to completion and availability.
The lack of political will exhibited in the late eighties greatly contributed to the allowance of AIDS to explode into a full-fledged U.S. epidemic. The recent Ebola and Zika outbreaks should motivate us to recognize that we are consistently at the threat of new viral outbreaks and epidemics. A similar “lack of political will” in supporting BSAs could easily be the catalyst to the next devastating epidemic.
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.