COVID-19 Drugs: Beta-Blocker Propranolol, A Cancer Drug Could Be Used To Treat COVID-19 According To Australian And Italian Study
: Researchers from the University of South Australia, Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS)-Italy and University of Campania-Italy in a new international study propose that beta-blockers could potentially be used to treat COVID-19.
COVID-19 disease which has now rapidly spread around the globe causing severe pneumonia is often linked to Acute Respiratory Distress Syndrome (ARDS) and hyperinflammatory syndrome. SARS-CoV-2 is highly contagious through saliva droplets. The structural analysis suggests that the virus enters human cells through the ligation of the spike protein to angiotensin-converting enzyme 2 (ACE2). The progression of COVID-19 has been divided into three main stages: stage I-viral response, stage II-pulmonary phase, and stage III-hyperinflammation phase. Once the patients enter stage III, it will likely need ventilation and it becomes difficult to manage. Thus, it will be of paramount importance to find therapies to prevent or slow down the progression of the disease toward stage III. The key event leading to hyperinflammation seems to be the activation of Th-17 immunity response and Cytokine storm. B2-adrenergic receptors (B2ARs) are expressed on airways and on all the immune cells such as macrophages, dendritic cells, B and T lymphocytes. Blocking (B2AR) has been proven, also in clinical settings, to reduce Th-17 response and negatively modulate inflammatory cytokines including IL-6 while increasing IFNγ. Non-selective beta-blockers are currently used to treat several diseases and have been proven to reduce stress-induced inflammation and reduce anxiety. For these reasons, the researchers speculate that targeting B2AR in the early phase of COVID-19 might be beneficial to prevent hyperinflammation.
The study findings were published in the journal: Frontiers in Immunology https://www.frontiersin.org/articles/10.3389/fimmu.2020.588724/full
Dr Nirmal Robinson from the University of South Australia cancer working with a team in Naples, has found evidence in animal models that the beta-blocker Propranolol helps suppress the spread of cancer in the lung which has an inflammatory profile very similar to COVID-19.
The team proposes additional studies and clinical trials to support their findings.
Head of the Cellular-Stress and Immune Response Laboratory at the Center for Cancer Biology, Dr Robinson, says Propranolol is commonly used to treat heart conditions, anxiety and migraine. Recent clinical trials have shown its effectiveness for other conditions, including cancer.
Dr Robinson told Thailand Medical News, "Patients with COVID-19 suffer from many abnormalities, including inflammation, because the SARS-CoV-2 virus disrupts the body's immune system. Beta-2 blockers could potentially reduce this inflammation and help rebalance the immune system."
Propranolol belongs to the groups of drugs known as beta blockers which are medicines that work by temporarily stopping or reducing the body's natural "fight-or-flight" response. In return, they reduce stress on certain parts of the body, such as the heart and blood vessels in the brain.
Beta blockers been suggested as a treatment option for auto
immune diseases such as rheumatoid arthritis.
Dr Robinson added, "SARS-Cov-2 enters the human cells through the protein ACE2, infecting the lower respiratory tract, causing profound inflammation and multi-organ failure. Patients with comorbidities, such as high blood pressure, diabetes and heart disease, are at much higher risk.”
To date other inflammation suppressors, including Tocilizumab (an immunosuppressive drug prescribed for arthritis) and Ruxolitinib (a drug used to treat the rare bone marrow blood cancer, myelofibrosis) have already been used to treat the more serious COVID-19 cases, although without much positive results.
Dr Robinson added, "We believe the beta-2-adrenergic pathway should be more deeply investigated as a possible target to reduce the inflammatory symptoms related to COVID-19. The next step is to perform clinical trials to explore an alternative therapy to treat COVID-19, based on the lessons we have learned from cancer.”
The team concluded, “Many supporting pieces of evidence show that the major symptoms of COVID-19 infection are associated with hyperinflammation over-activation of Th17 response. Indeed, treatments known to reduce Th17 response such as Tocilizumab and Ruxolitinib have been already used to treat Covid-19 patients in phases II and III. β2-AR signals have been described to have a central role in rheumatoid arthritis in promoting inflammation and Th17 response. Non-selective beta-blockers have been used in clinical settings to reduce inflammation and Th17 response. In addition, the non-selective beta-blocker propranolol blocks AT1 induced expression of IL-6, NFkB, TNF, IFN-γ, VEGF, and Metalloprotease Engagement. We believe that β2-AR signals might be a valuable target for new strategies aiming to block or slow down the transition from the early phases (I and IIa) of COVID-19 to phase III by reducing the activation of Th17 response and inflammatory cytokine release and prevent venous thromboembolism. For these reasons we would like to point out the importance to perform further preclinical and clinical studies to explore this opportunity.”
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