Two Common Over-the-Counter Compounds Reduce COVID-19 Virus Replication by 99% in Early Testing

Preliminary tests have found a few over-the-counter compounds to inhibit the virus that causes COVID-19, researchers at the University of Florida Health have discovered.

The combination includes diphenhydramine, an antihistamine used for allergy symptoms. When combined with lactoferrin, a protein found in cow and breast milk, the compounds were shown to hinder the SARS-CoV-2 virus during tests in monkey cells and human lung cells.

The findings of David A. Ostrov, Ph.D., an immunologist and associate professor in the UF College of Medicine’s division of pathology, immunology and laboratory medicine, and his colleagues, are published in the journal Pathogens.

“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.

Molecular linkage of sigma-2 receptor ligands exhibiting antiviral activity against SARS-CoV-2. Credit: University of Florida

Ostrov already knew from his previous research with colleagues at UF that diphenhydramine might be effective against the SARS-CoV-2 virus. The latest discovery stems from a routine meeting of scientists with the Global Virus Network’s COVID-19 task force. An investigator presented unpublished data on federally approved compounds that inhibit SARS-CoV-2 activity, including lactoferrin.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 combining it with diphenhydramine and started working with the idea. In laboratory 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%.

The findings, Ostrov said, are a first step in developing a formulation that could be used to accelerate recovery from COVID-19. It also opens up prospects for further research through an academic-business partnership for human clinical trials focused on the prevention of COVID-19. Additional research on the effectiveness of the compounds for the prevention of COVID-19 is already underway in mouse models.

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’ stress response machines, including sigma receptors, to replicate in the body. Disrupting that signaling seems to be the key to inhibiting the virus’ potency.
“We now know the detailed mechanism of how certain drugs inhibit SARS-CoV-2 infection,” Ostrov said.

Data from the experiments show that a highly specific sigma receptor binding drug candidate (with analgesic properties) and formulated combinations of over-the-counter products (such as diphenhydramine and lactoferrin) have the potential to inhibit viral infection and reduce recovery time from COVID-19, conclude. the researchers.

While the findings are encouraging, Ostrov warns against self-medicating with diphenhydramine or lactoferrin for the prevention or treatment of COVID-19. The type of lactoferrin used in the study is slightly different from the type commonly available to consumers, he noted. Lactoferrin is often used as a supplement to treat stomach and duodenal ulcers, among other things.

Reference: “Highly specific Sigma receptor ligands exhibit antiviral properties in SARS-CoV-2 infected cells” by David A. Ostrov, Andrew P. Bluhm, Danmeng Li, Juveriya Qamar Khan, Megha Rohamare, Karthic Rajamanickam, Kalpana K. Bhanumathy, Jocelyne Lew, Darryl Falzarano, Franco J. Vizeacoumar, Joyce A. Wilson, Marco Mottinelli, Siva Rama Raju Kanumuri, Abhisheak Sharma, Christopher R. McCurdy, and Michael H. Norris, Nov. 20, 2021, Pathogens.
DOI: 10.3390/pathogens10111514

Scientists from UF’s Emerging Pathogens Institute, College of Pharmacy and Clinical and Translational Science Institute, the University of Saskatchewan and the Saskatchewan Cancer Agency collaborated on the study.