A promising drug could prevent cardiovascular damage in Covid-19 patients
Posted on May 7, 2021 by Microbiology Society
At the Microbiology Society's Annual Conference Online 2021, Danielle Nader, PhD Student at the Royal College of Surgeons in Ireland (RSCI), presented her findings that a new drug target could protect against vascular damage in Covid-19 patients. Find out more about Danielle's research in this blog.
Danielle Nader and colleagues at the RSCI have identified a drug which could block SARS-CoV-2 from entering the endothelial cells that line blood vessels, including arteries and veins, to protect them against damage by the virus. The research found that the drug Cilengitide, which was originally developed to treat cancer, blocks a protein called αVβ3, which SARS-CoV-2 needs to enter certain human cells.
“Our work has demonstrated that this receptor is targeted by the spike protein of SARS-CoV-2, which functions to attach the virus to host cells in the first stage of infection. Cilengitide was capable of preventing the spike protein from binding to vascular endothelial cells, which is the final barrier before the virus can enter the bloodstream,” explained Danielle.
Endothelial cells are found throughout the body, including in the respiratory, cardiovascular, endocrine, gastrointestinal and genitourinarysystems. An area of the SARS-CoV-2 spike protein, called Arg-Gly-Asp (RGD), must bind to αVβ3 on the surface of these cells to enter and multiply. As well as allowing the SARS-CoV-2 virus to enter host cells, the spike protein is the main target of the immune system, including immunity generated by all current SARS-CoV-2 vaccines. Blocking αVβ3 and preventing RGD from binding can protect cells from infection.
Cardiovascular disease, such as high blood pressure or a history of heart attacks, increases a person’s risk of death from Covid-19. Nader hopes that using small doses of Cilengitide could prevent the virus from entering the bloodstream and improve patient outcomes: “We are currently investigating the possibility of testing Cilengitide in a small human clinical trial using COVID-19 patients.” Previous trials of the drug, which was originally developed as a treatment for brain cancer, showed that the drug has few side-effects and is safe for use in people, making it a promising treatment option. “Cilengitide displayed very low toxicity during clinical trials and was well-tolerated by volunteers. In addition, we do not anticipate any adverse effects on patients since we administer exceedingly small doses and still obtain positive results,” said Danielle.
In addition to the immediate effects of Covid-19 infection on the cardiovascular system, there are concerns that SARS-CoV-2 infection could have longer-term impacts on cardiovascular health. “Although the long-term effects of COVID-19 remains uncertain, a 10-year follow up of patients that recovered from the 2003 SARS-CoV epidemic revealed nearly 35 % had severe downstream cardiovascular side effects that included strokes or heart attacks. It should be expected that patients with COVID-19 may also experience similar long-term chronic heart damage” she explined.
SARS-CoV-2 is not unique in using αVβ3 to infect human cells, and Cilengitide could be a useful treatment strategy against a number of infectious diseases, according to Danielle: “Several microbes have developed similar interaction pathways to SARS-CoV-2 by targeting the αVβ3 receptor. This assists in their binding and infection process. These include the major bacterial pathogens, Staphylococcus aureus and Escherichia coli, as well as adenoviruses that cause respiratory illnesses including common colds and pneumonia. Therefore, αVβ3 represents a promising target for a wide-spread number of pathogens. Viruses are capable of mutating extremely rapidly, and a simple single-letter mutation could result in the acquisition of a new receptor – similar to what we have identified in SARS-CoV-2.”
Danielle’s presentation, “Targeting the evolutionary RGD motif in the spike protein of SARS-CoV-2 serves as a novel treatment option to prevent vascular damage during COVID-19” took place at 16:15, on Monday, 26 April, 2021 as part of the session SARS-CoV-2 and the COVID-19 pandemic: molecular virology and immunology.
Find out more about this research in the recently published article A new perspective in sepsis treatment: could RGD-dependent integrins be novel targets?