A possible therapeutic approach to COVID-19

As the COVID-19 pandemic persists, the search for effective and accessible treatments continues. Researchers from the university of Kentucky, Lexington, propose a potential treatment option for COVID-19, consisting of a combination of DPP4 inhibitors and spironolactone. This form of combination therapy, they propose, is likely to mitigate COVID-19 complications and infections without any adverse side effects. The medications are already prescribed regularly in developed countries.

SARS-CoV-2, the virus associated with the COVID-19 disease, achieves cell entry primarily via interacting with ACE2 and possibly DPP4 cell receptors. The S glycoprotein of SARS-CoV-2 binds to ACE2, which leads to S protein priming, and eventually, viral fusion into the host cells. Certain proteases, such as TMPRSS2 and ADAM metallopeptidase domain 17 (ADAM17), can expedite this process as well. TMPRSS2 and ADAM17 can detach ACE2 from the cell membrane and produce soluble ACE2. SARS-CoV-2 has high affinity towards ACE2, and the attachment of SARS-CoV-2 to soluble ACE2 increases the weight and diameter of the virus. Consequently, this accelerates the process of virus entry into the host cells.

Obesity, which is a risk factor for COVID-19, causes shedding of ACE2 receptors and increases soluble ACE2 levels in the bloodstream. While membrane-bound ACE2 exhibits protective roles against SARS-CoV-2 infection, soluble ACE2 appears to enhance its infectivity by affecting the biophysics of the viral particles and facilitating viral cell entry. This explains why obesity is a risk factor.

Spironolactone is a routinely prescribed drug for health problems such as heart failure, kidney disease and blood pressure. Spironolactone reduces TMPRSS-2 expression, inhibits ADAM17, increases ACE2 expression on cell membrane and decreases soluble ACE2 levels. This appears to be beneficial in terms of reducing COVID-19 infectivity. Furthermore, sitagliptin, a DPP4 inhibitor which is prescribed as an anti-diabetic medication, can potentially block a possible route of viral entry. Therefore, the combination of DPP4 inhibitors (such as sitagliptin) and spironolactone seems to be an effective, feasible treatment option for COVID-19. The complete article has been published in Endocrine, Metabolic & Immune Disorders - Drug Targets.

To access the article, please visit: http://www.eurekaselect.com/article/119929

Authors: Artin Asadipooya, Kamyar Asadipooya

University of Kentucky, Lexington, KY, USA