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Intranasally Administered Small Peptide That Blocks COVID-19 Spike Protein Interaction with ACE-2 Shows Success in COVID-19 Therapy in Mouse Model

In a study published online on January 11, 2021 in the Journal of Neuroimmune Pharmacology, mouse models with COVID-19 showed positive results when a small peptide was introduced nasally. The peptide proved effective in reducing fever, protecting the lungs, improving heart function, and reversing “cytokine storm”--a condition in which an infection triggers the immune system to flood the bloodstream with inflammatory proteins. The researchers also report success in preventing the disease from progression. The open-access article is titled “ACE-2-interacting Domain of SARS-CoV-2 (AIDS) Peptide Suppresses Inflammation to Reduce Fever and Protect Lungs and Heart in Mice: Implications for COVID-19 Therapy.” "This could be a new approach to prevent SARS-CoV-2 infection and protect COVID-19 patients from breathing problems and cardiac issues," said Kalipada Pahan, PhD, the Floyd A. Davis Professor of Neurology at Rush University Medical Center and a Research Career Scientist at the Jesse Brown VA Medical Center, both in Chicago, understanding the mechanism is proving important to developing effective therapies for COVID-19." Many COVID-19 patients in the intensive care unit (ICU) suffer from cytokine storm that affects lungs, heart, and other organs. Although anti-inflammatory therapies such as steroids are available, very often these treatments cause immunosuppression. "Because SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) for entering into the cells, we have designed a hexapeptide corresponding to the ACE2-interacting domain of SARS-CoV-2 (AIDS) to inhibit the binding of virus with ACE-2," Dr. Pahan said. "AIDS peptide inhibits cytokines produced by only SARS-CoV-2 spike protein, not other inflammatory stimuli, indicating that AIDS peptide would not cause immunosuppression. We found that after intranasal treatment, AIDS peptide reduces fever, protects lungs, normalizes heart function, and enhances locomotor activities in a mouse model of COVID-19."

Although vaccine is available, COVID-19 could potentially morph into a seasonal and an opportunistic event. For example, despite flu vaccination, about 40,000 to 50,000 people die each year in the United States from the flu.

Therefore, a specific medicine for reducing SARS-CoV-2-related inflammatory events and taking care of respiratory and cardiac issues of COVID-19 will be necessary for better management of COVID-19 even in the post-vaccine era.

"If our AIDS peptide results can be replicated in COVID-19 patients, it would be a remarkable advance in controlling this devastating pandemic," Dr. Pahan said.

Common symptoms of COVID-19 are fever, cough, and shortness of breath. With a mortality rate of approximately 4-5 percent, COVID-19 is 10 times more lethal than flu. While anyone is susceptible to COVID-19, those over 60 years of age and those with preexisting conditions, such as hypertension, obesity, asthma, or diabetes, are more vulnerable to severe symptoms. Currently it appears that COVID-19 is more lethal in men than women. To date, about 2 million people throughout the world have died due to COVID-19.

Other authors of the article are Dr. Ramesh Kumar, Dr. Malabendu Jana, Dr. Debashis Dutta, and Dr. Sumita Raha from Rush University Medical Center; and Dr. Rama K. Mishra from Northwestern University.

[News release] [Journal of Neuroimmune Pharmacology article]