CAPE TOWN - It seems incredible in this age of pandemics that a dozen broad-spectrum antiviral drugs have been largely ignored in the fight against Covid-19. This class of drugs works by inhibiting a critically-important human protein called nuclear-factor kappa-binding - NF-kB for short.
NF-kB exists in the cytoplasm of every cell and does two main things related to disease. When it is released from its inhibitor I-kB, it increases both inflammation and viral replication. That is why cells carefully restrain it. Cells lock it safely away in the cytoplasm to prevent it from causing these two negative effects that occur when it is released and moves from the cytoplasm into the nucleus. When its inhibiting bond with I-kB – inhibitor of kB - is dissolved and it is released, NF-kB greatly increases both inflammation and virus production. The NF-kB release-inflammation-viral replication cycle becomes a self-reinforcing positive feedback loop. Reducing this stimulant protein, keeping it locked away, attached to its inhibitor, is important in fighting viral infections and limiting the damaging inflammation it causes. That is why NF-kB inhibitor drugs (NF-kBIs) are so important.
However, during the entire Covid-19 pandemic almost no one has mentioned NF-kB or NF-kBIs except for dexamethasone and other strong anti-inflammatory steroid drugs like prednisone and hydrocortisone. These steroid drugs have serious side effects and can be used only for a limited time, about two weeks. What most people, including many doctors, do not realize is that these commonly known anti-inflammatory drugs also work as antiviral drugs. They are dual purpose. NF-kBIs form a whole class of drugs we have failed to utilize in the past to fight viral infections. It is past time we did. Millions of lives have been lost due to this oversight.
In 1990 and 1991 Dr Donald Kotler of Columbia University published two abstracts that showed that 5-ASA, an aspirin (ASA) analogue, could inhibit HIV replication by about 65% as well as AZT, the first anti-AIDS drug. A dozen years later, research by me and Dr Elopy Sibanda, an immunologist in Zimbabwe, showed that aspirin alone could increase CD4 count twice as high and for twice as long – for one year – as AZT could.
However, compared to many NF-kBIs, aspirin is relatively weak. Some NF-kBIs are dozens of times stronger than aspirin at reducing NF-kB. Thus, a whole class of drugs exists that doctors mostly have not been using to treat viral infections and save lives. NF-kBIs include both steroid and non-steroid anti-inflammatory drugs (NSAIDs). Who knew that common anti-inflammatory drugs also work as antiviral drugs? Now we do.
So why are we not using them, especially when deadly viruses strike?
The main reason even doctors are not informed about this large class of variously powerful broad-spectrum antiviral drugs is that pharmaceutical companies want to develop specific antiviral drugs for each new virus that emerges so they can charge excessive prices for those new drugs, just like they did with AZT. They want to ignore or coverup the fact that relatively cheap existing drugs are somewhat effective against almost all viruses because almost all viruses stimulate the release of NF-kB to boost their own replication. NF-kB is the primary stimulant or fuel for viral replication. This becomes a self-sustaining cycle. The more NF-kB, the more virus production. The more virus, the more NF-kB is released. Physicians need to interrupt this escalating cycle.
An effective way to do that is by administering NF-kB inhibitor drugs. When more specific antivirals are eventually developed, they can be added as a combination therapy. Totally disregarding what should be an obvious approach to treating viral infections, pharmaceutical companies want to develop an anti-X drug for X-virus disease, and an anti-Z drug for Z-virus disease. That way they can charge exorbitant prices for those new virus-specific drugs. The more deadly the virus, the higher the price. They do not want people to know that behind the curtain of pharmaceutical knowledge a dozen drugs already exist that are effective against most viruses. The unfortunate consequence is that hundreds of thousands of people die before those specific, perhaps only slightly more effective drugs are developed, produced, and distributed.
In the case of AIDS, it took fifteen years to develop those. With Covid-19 it has taken over two years before those new drugs have started to make it to market. One million Americans died while only steroid NF-kBI drugs have been used for restricted two-week periods, only once the disease was advanced. Thus, other non-steroid anti-inflammatory NF-kBI drugs with less severe side effects were totally ignored. These could have been used from the initial onset of symptoms to slow Covid disease progression from the beginning. That was a tragic, strategic, medical oversight. What will happen when the next, perhaps more deadly pandemic strikes? Will governments again ignore life-saving drugs? Yes. They will unless a naïve public wakes up to this unethical medical negligence.
In 2004 researchers at the University of Texas developed a list of broad-spectrum anti-viral NSAID drugs and their relative power to inhibit NF-kB they reported in a scientific article in the cancer journal Oncogene (23, 9247-9258). They tested the strength of various NF-kBIs relative to aspirin, with aspirin assigned a strength of 1.0. That article reported how the following NSAIDs, plus the steroid dexamethasone, compared to aspirin’s inhibition of NF-kB. Aspirin (1.0), ibuprofen (1.6), sulindac (1.9), phenylbutazone (4.5), naproxen (6.0), indomethacin (9.5), diclofenac (14.6), resveratrol (67.5), curcumin (131.0) dexamethasone (210.0), celecoxib (236.0), tamoxifen (567.0). Although the nutritional supplement selenium also inhibits NF-kB, it was not tested.
Selenium works against viral replication by multiple immunological and cellular mechanisms. Its ability to specifically inhibit NF-kB may fall towards the lower end of this scale. However, selenium’s primary function against viral disease is not as an NF-kBI, but rather its ability to replace the selenium lost due to viral replication, and its ability to increase CD4 count by acting directly on the thymus gland.
While aspirin can increase CD4 count significantly for up to one year, I am not aware if other NF-kBIs demonstrate that same effect. Some may and some may not. However, selenium supplementation can continue to help maintain a high CD4 count for years. It is the strongest medicinal agent to increase CD4 because it acts directly on the thymus to do so.
Selenium is unique in that it is both the key element required for the functioning of the immune system and for the formation of cellular antioxidants that keep every cell in the body detoxified, clean, and healthy. If any one thing at the subcellular level can be called the key to good health, selenium is it.
Viruses cause the diseases they do largely by attacking the selenium contained in cells and thereby disabling their antioxidant systems, damaging cells and tissues. Viruses require selenium to form their protective envelopes that act like skins to protect them from the inter-cellular environment into which they are released. Just like cells, enveloped viruses cannot survive without selenium containing proteins to protect them.
Viruses acquire that selenium by attacking and destroying cellular antioxidants where selenium is concentrated – stealing it for their own use. Selenium is concentrated in the cells and organs of the immune system including CD4 and macrophage cells, and the thymus, spleen, kidneys, and liver. As viral replication increases, selenium is gradually depleted from the immune system and the body. When selenium levels in the body fall, CD4 counts tumble in tandem.
CD4 white blood cells are considered the generals of the immune system army. They direct and control the many different types of cells that constitute the immune system. When CD4 counts fall to dangerously low levels the immune system spins out of control and collapses. CD4 cells live for only four days, so millions must be replaced each day. Viral diseases like HIV, Ebola, Marburg, Hantavirus, and Covid-19 that deplete selenium from the immune system and cause CD4 counts to plummet and prooxidant cytokines like interleukin-6 (IL-6) to increase, all follow a common disease pathway. Damaged cells that have lost their antioxidant protection die, spilling toxins into the blood stream.
That contributes to sepsis or blood poisoning. Cellular and tissue damage, the resultant toxins, and loss of selenium, and the cytokine storm initiated by increased levels of IL-6, all contribute to multiorgan failure that includes kidney, liver, lung, and heart failure. The final consequence is death. Selenium supplementation at adequate doses has been shown to reduce and even reverse multiorgan failure by up to 50%. It is remarkable selenium supplementation still can be so effective even at this final, often fatal phase brought on by the cascade of events that starts with the loss of selenium due to rapid viral replication.
The key to reversing this deadly microbiological cascade is maintaining control of the immune system by maximizing CD4 count through selenium supplementation.
CD4 cells are manufactured and processed in the thymus gland from naïve CD cells that originate in the bone marrow. The thymus can process naïve cells into either CD4, or CD8 cells, depending on the signals it receives. The dominant signal is based on the level of selenium in the body. When selenium is low the thymus produces more CD8 and fewer CD4. When levels are high it produces more CD4 and less CD8. Different viruses require different amounts of selenium, so depletion occurs at different rates.
Elongated Ebola and Marburg filoviruses require more selenium atoms and replicate faster than most. When the rate of viral replication soars out of control, in part due to the loss of selenium and CD4, the level of selenium and CD4 production can drop precipitously. The collapse of the entire immune system can be relatively swift, as with Ebola.
Scientists have shown that in Covid-19, 100% of those who have severe disease or die are deficient in selenium. The same is true of AIDS, Ebola, Marburg, Hantavirus and many, probably most deadly viral diseases. Selenium deficiency increases rapidly as Covid-19 progresses, showing it to be the key nutritional deficiency caused by SARS-2, propelling physiological decline as viral load escalates.
Between early 2020 and the end of March 2022, one million Americans died of Covid-19. That is a third more deaths than in America’s costliest war, the Civil War. Just as in 2014 when a moderately high dose of selenium reduced the mortality rate of Ebola in Liberia by approximately half, if an adequate dose of selenium had been used against Covid-19 at least half of those American deaths could have been prevented. If moderate to strong NF-kB inhibitor NSAID drugs had been used in conjunction with selenium from initial infection, even more lives should have been saved.
In 1896 Democratic presidential candidate William Jennings Bryan made an impassioned Cross of Gold speech at the Democratic convention in Chicago highlighting how the common person in America had been financially burdened by a currency tied to the gold standard that was causing widespread depression in a national economy still largely tied to agriculture. Today candidate Bryan might make a Cross of Pharmaceuticals speech highlighting the fact that scientifically based beneficial health information and life saving medicines are obscured by and for the benefit of huge corporations in their rush for excessive profits for the pharmaceutical-industrial-complex. This has cost American families hundreds of thousands of lives and extreme medical bills, bankrupting many. It has cost the national treasury trillions.
Today it is all the rage to talk about the need for pandemic preparedness. But how can America and the world be prepared for the next pandemic if we continue to ignore science and fail to learn the obvious lessons of this and previous epidemics and pandemics?
A common nostrum is that military generals always prepare to fight the last war. But even if one prepares to fight that last war, if they fail to update their military science with the latest technological understanding, they are sure to fail. It is essential to understand how all the pieces of the viral-immunity puzzle fit together, and if a significant piece of that puzzle is missing. Unfortunately, in our response to Covid-19 to date, it has been. We urgently need to remedy that for the coming endemic Covid phase that may last for years or a lifetime.
America and the World Health Organization have failed to utilize twenty-year-old scientific knowledge in the face of the AIDS pandemic, the Ebola epidemic, Zika, and now the SARS-2 pandemic. If they have failed to learn these lessons for over twenty years, when will they ever learn? How many more people must die in this pandemic, the next one, and the one after that due to this negligence? Serial pandemic failure by health authorities is a menace to society and a costly burden for all to bear.
Where is William Jennings Bryan now that we need him? How long must Americans bear this heavy cross and the cost of excess profits for the pharmaceutical industry? How much longer must thousands continue to die when effective treatments sit on the pharmacy shelf, but knowledge of their use is hidden behind the pharmaceutical curtain? When will enough dying be enough?
* Howard S. Armistead is the director of the Selenium Education and Research Centre
Cape Times