A Novel Intervention for Long COVID: The Combination of Dopamine D1 Partial Agonists and Candesartan

Abstract

Adonis Sfera*, Jacob Anton and Sabine Hazan

Like previous pandemics, COVID-19 has been succeeded by well-documented postinfectious sequelae, colloquially known as “long COVID”. This syndrome, manifested by chronic fatigue, post-exertional malaise, shortness of breath, myalgia, and concentration difficulties, may last for many months after the acute phase of illness. Long COVID affects all aspects of a patient’s life, including work, rest, and activities of daily living, placing a large financial burden not only on the individual but also on families, and the society at large.

Like other viruses, including Human Immunodeficiency Virus (HIV), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may thrive in viral reservoirs, likely comprised of senescent endothelial cells, macrophages, and microglia that shield the virus from neutralizing antibodies, maintaining a low-grade SARS-CoV-2 infection. Since senescent cells upregulate Angiotensin-Converting Enzyme 2 (ACE- 2), the SARS-CoV-2 entry portal, this protein facilitates viral ingress in host cells.

The invention described here consists of a combination of dopamine D1 receptor antagonists or partial agonists, such as SKF 38393, and angiotensin receptor blocker, candesartan, for long COVID. This strategy is based on the hypothesis that the SARS-CoV-2 virus thrives in senescent endothelial cells, macrophages, and microglia and can be reactivated under favorable circumstances. Furthermore, as both angiotensin II and dopamine D1 receptors have been implicated in cellular senescence, manipulating these proteins may avert viral persistence in reservoirs and the residual COVID-19 symptoms.