A new potential therapy for COVID-19 developed by researchers at Rush University Medical Center has shown success in preventing the disease’s symptoms in mice.
In a study, mouse models with COVID-19 showed positive results when a peptide (chain of amino acids) was introduced nasally.
The peptide proved effective in reducing fever, protecting the lungs, improving heart function and reversing cytokine storm – the immune system overreacting to an infection and flooding the bloodstream with inflammatory proteins.
The researchers also report success in preventing the disease from progression in the report of their results published Jan. 11 in the Journal of Neuroimmune Pharmacology.
SARS-CoV-2, the virus that causes COVID-19, binds to an enzyme called ACE2 to enter and infect human cells. In response, the research team designed a hexapeptide (a peptide with six amino acids) that inhibits the virus from binding with ACE2.
“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, Ph.D., the Floyd A. Davis Professor of Neurology at the Rush University Medical Center and a research career scientist at the Jesse Brown VA Medical Center, who led the study.
Many patients with COVID-19 in intensive care units suffer from cytokine storm, which affects lungs, heart and other organs. Although anti-inflammatory therapies such as steroids are available to treat the problem, very often these treatments cause suppression of the immune system.
“The peptide inhibits cytokines that only are produced by the SARS-CoV-2 spike protein, not other inflammatory stimuli, indicating that this peptide would not cause immunosuppression,” Pahan said.
Although vaccines for COVID-19 are becoming available, their distribution nationally and globally will take months and possibly years in some part of the world. In addition, vaccines may not entirely prevent the spread of COVID-19.
For example, despite flu vaccination, about 40,000 to 50,000 people die each year in United States from the flu.
Therefore, a specific medicine for reducing inflammatory events and treating respiratory and cardiac problems caused by COVID-19 will be necessary for better management of the disease even in the post-vaccine era.
“If our peptide results can be replicated in COVID-19 patients, it would be a remarkable advance in controlling this devastating pandemic,” Pahan said.
Common symptoms of COVID-19 are fever, cough, and shortness of breath and with a mortality rate of around 4–5%, it is more than 10 times lethal than the flu.
While anyone is susceptible to COVID-19, the ones over 60 or with preexisting conditions, such as hypertension, obesity, asthma, or diabetes, are more vulnerable to severe symptoms (Ledford 2020; Machhi et al. 2020). Until now, no effective therapy is available to tackle this viral pandemic.
Entry of SARS-CoV-2 into the host cells is probably the most important event in COVID-19 disease process. Angiotensin-converting enzyme 2 (ACE2), the main effector of the classical renin-angiotensin system, is a cell surface receptor that is predominant in lung, heart and kidney (Zaman et al. 2002).
Although the prototype function of ACE2 is to convert angiotensin II (AngII), a vasoconstrictor, to Ang1-7, a vasodilator, and thereby to play an important role in the pathophysiology of cardiovascular diseases (Vickers et al. 2002; Zaman et al. 2002), recently, ACE2 came to renewed attention due to its requirement by COVID-19 for entering into host cells.
It is found that COVID-19 binds to ACE2 via the S protein on its surface (Machhi et al. 2020; Stower 2020). During infection, the S protein is cleaved into S1 and S2 subunits and the S1 subunit encompasses the receptor-binding domain (RBD). Therefore, this subunit permits COVID-19 to directly attach to the peptidase domain of ACE2 (Ledford 2020; Stower 2020).
Since ACE2 is a beneficial molecule, either inhibiting or knocking down of ACE2 is not a valid option. Therefore, for specific targeting of the binding between ACE2 and SARS-CoV-2, we designed a peptide corresponding to the ACE2-interacting domain of SARS-CoV-2 (AIDS) that inhibited the binding between ACE2 and SARS-CoV-2 spike S1 and specifically reduced spike S1-mediated activation of NF-κB and induction of IL-6 in lung cells without modulating double-stranded RNA (poly IC)-, HIV-1 Tat-, and flagellin-mediated NF-κB activation and IL-6 expression. Moreover, intranasal administration of AIDS peptide reduced fever, protected lungs, improved heart function, and enhanced locomotor activities in SARS-CoV-2 spike S1-intoxicated mice, highlighting the therapeutic promise of AIDS peptide in COVID-19.
More information: Ramesh K. Paidi et al. 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, Journal of Neuroimmune Pharmacology (2021). DOI: 10.1007/s11481-020-09979-8
