A pair of over-the-counter compounds has been found in preliminary tests to inhibit the virus that causes COVID-19, University of Florida Health researchers have found.

The combination includes diphenhydramine, an antihistamine used for allergy symptoms. When paired with lactoferrin, a protein found in cow and human milk, the compounds were found to hinder the SARS-CoV-2 virus during tests in monkey cells and human lung cells. The findings by David A. Ostrov, Ph.D. are published in the journal Pathogens. Results of the study:

Sigma Ligands Inhibit SARS-CoV-2-Mediated Cell Death, Intracellular Replication, and Infectivity. These data demonstrate that combinations of two over-the-counter compounds, lactoferrin and diphenhydramine, with well characterized safety profiles, have synergistic effects on the inhibition of SARS-CoV-2

“We found out why certain drugs are active against the virus that causes COVID-19. Then, we found an antiviral combination that can be effective, economical and has a long history of safety,” Ostrov said. Due to his earlier research with colleagues at UF, Ostrov already knew diphenhydramine [Benedryl] was potentially effective against the SARS-CoV-2 virus. The latest discovery has its roots in a routine meeting of scientists with the Global Virus Network’s COVID-19 task force.

One researcher presented unpublished data on federally approved compounds that inhibit SARS-CoV-2 activity, including lactoferrin. Like diphenhydramine, lactoferrin is available without a prescription. Ostrov thought about pairing it with diphenhydramine and ran with the idea. In lab tests on human and monkey cells, the combination was particularly potent: Individually, the two compounds each inhibited SARS-CoV-2 virus replication by about 30%. Together, they reduced virus replication by 99%. [Lactoferrin, found in colostrum of mother’s milk in all animals, is such a powerful immune-boosting nutrient that in 2012 the U.S. Centers for Disease Control and Prevention (CDC) advised mothers not to breastfeed their babies. Breast milk contains high amounts of lactoferrin, a fact that infringes on profits for pharmaceuticals and formula milk.

Lactoferrin’s job is to grab up the free iron in our bodies, and carry it to the cells where it can be used. Lactoferrin helps with viruses by getting in their way. Think of the cells in your body as little warehouses that have loading docks where trucks pull up to load and unload their cargo. It turns out that lactoferrin and some viruses require the use of the same specific loading docks at each of your cells, and lactoferrin gets priority.

To get you sick a virus docks with a cell, offloads its own DNA into the cell, then forces the cell to massively replicate that DNA to create more of the virus. Eventually it overwhelms your body’s immune system. If a virus cannot dock with a cell, it cannot replicate and make you sick, and the longer that the virus floats free the higher the chance that your body’s white blood cells and other defenses will catch it and destroy it.

To establish their findings, the research team focused on proteins expressed in human cells known as sigma receptors. In COVID-19 cases, the virus “hijacks” the  stress-response machinery, including sigma receptors, in order to replicate in the body. Interfering with that signaling appears to be the key to inhibiting the virus’s potency.

“We now know the detailed mechanism of how certain drugs inhibit SARS-CoV-2 infection,” Ostrov said. Data from the experiments show that formulated combinations of over-the-counter products [such as diphenhydramine and lactoferrin] have the potential to inhibit virus infection and decrease recovery time from COVID-19, the researchers concluded.



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