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MDIBL’s Work in 2022 Includes a New Way To Prevent COVID-19 Infection

  • January 13, 2023

Over the course of the year just past, MDI Biological Laboratory’s researchers continued to push the frontiers in the biology of aging, repair, and regeneration, expanding our knowledge of how to protect and extend healthy lifespans.

The 19 peer-reviewed research papers by MDIBL faculty and post-doctoral researchers included work that brought their expertise to bear on other pressing issues as well, including saving the lives of people exposed to Covid-19.

Laboratory President Hermann Haller, M.D., and partners from Germany’s Hannover Medical School in the fall published research showing that a well-known, inexpensive substance could be highly effective in preventing infections with the Covid-19 virus, SARS-CoV-2.

Existing vaccines against the virus are potent boosters of the immune system and help us fight the virus. But they do not prevent infection. That’s why many vaccinated people may still get the virus and go on to suffer from the disease.

The Haller group’s findings point the way to preventing infection altogether by inhibiting the entry of the virus into our cells.

The therapeutic compound is called calcium dobesilate (CaD), and the Haller group found that it interferes with the prolific infectiousness of protein spikes on the surface of the coronavirus – the ones that make it look like a bristling naval mine.

CaD, they found, prevents the spikes from gaining a foothold on the exterior of endothelial cells that line smaller blood vessels of the vascular system, such as capillaries. That reduces SARS-CoV-2’s chances to move beyond its usual first line of attack, our bronchial upper airways, and spread into the blood system to set off a cascade of Covid-19’s deadliest complications.

How did MDIBL researchers get involved with Covid-19? Haller is a leading researcher in kidney repair and regeneration, and an inventor of new tools for investigating substance effects on blood vessels in the kidneys and vascular endothelia.

The vascular endothelia are the main target of Covid-19. Haller’s expertise on small blood vessels, and endothelial cells came together with his laboratory skills to produce new and promising insights about the pathways that aid infection with SARS-CoV-2.

Haller and his colleagues found that introduction of CaD into the vascular environment has a masking effect that blocks the spike proteins’ ability to bind with a substance on the cell surface, heparan sulfate, that otherwise facilitates viral incursions into host cell endothelia.

We combined our expertise on endothelial cells and their role in vascular health with observations about how Covid-19 gains entry into the body,” Haller says. “We have worked with CaD in other diseases and could describe for the first time a novel mechanism to prevent infection. Our findings delineate a novel strategy to stop SARS-CoV-2’s first attempts to get in.”

The scientists had previously found that at the molecular level CaD can interfere with electrostatic interactions that charge a spike protein’s ability to bind with heparan sulfate. They decided to test CaD at the cellular level and beyond.

This time out, they created an innovative cell-culture flow system that depends on tiny ”microfluidic” channels and chambers to provide a robust physiological environment– an innovative laboratory setup to sustain a stable surface of endothelial cells and the expression of heparan sulfates. The microvessels were then exposed to partial (and non-deadly) pseudoviral particles, and treated with CaD.

And that did, in fact, measurably inhibit spike protein and heparan sulfate interactions. After tests to control for potential general toxicity of CaD and other comparisons, they moved on to ex vivo tests with functioning mouse kidneys, meeting further success.

“Together our data suggest that spike protein interacts with intact (heparan sulfate) glycocalyx thus facilitating cell infection,” they concluded. “CaD prevents spike interaction with HS and can protect the cells from being infected.”

The implications are important since this could be the first preventive treatment for COVID-19.

CaD is already approved as a therapy for several blood-vessel disorders, and it avoids unwanted side-effects such as increased blood coagulation. It can be delivered as a nasal spray – a direct intervention at COVID 19’s first contact in the upper airway — but it can also be taken orally for a more systemic approach.

Haller and his colleagues believe the latter may be where CaD offers the most exciting potential. He says that CaD therapy with patients who are in the early stages of infection could be a powerful bulwark against spread into endothelial cells that line the smallest components of the blood system — the arterioles, capillaries and venules that are most directly involved with blood-tissue exchange.

That microvasculature is a prime suspect involved in not only the deadliest short-term effects of Covid-19 infection, but also in the still-unsolved mysteries of “long Covid.”

“A clinical study of CaD’s therapeutic potential in humans is under way in Europe”, Haller says. “Our experiments and these findings are an excellent example of translational research at MDIBL – how basic research can have clinical implications if you combine an understanding of molecular and cellular pathways with the most urgent medical needs of our times.”