Could Oral Phosphodiesterase 5 Inhibitors Have a Potential Adjuvant Role in Combating COVID-19 Infection?

Abstract

Introduction The recent global outbreak of coronavirus disease 2019 (COVID-19) has become a pandemic with a lot of sufferers. Excessive inflammation, exaggerated immune response, with ultimate apoptosis contribute to COVID-19 pathology that progress to acute lung acute respiratory distress. Objective To shed a light on the likely benefits of the oral phosphodiesterase 5 (PDE5) inhibitor adjuvant role in combating COVID-19 infection. Methods A literature review was performed in the PubMed/Medline database, Scopus, Cochrane Library, EMBASE, Academic Search Complete, Google Scholar, and CINAHL databases using the keywords COVID-19; phosphodiesterase-5 inhibitors; cytokine storm; respiratory distress. Results Despite the worsening trends of COVID-19, still no drugs are validated to have significant clinical efficacy in the treatment of patients with COVID-19 in large-scale studies. While the progress toward a curative agent and/or vaccine is certainly hopeful, the principal limiting factor in such public health emergencies is always the time. Therefore, a preexisting licensed therapeutic(s) might offer a reprieve to the healthcare systems operating at the edge of capacity. In this context, the innovation of oral PDE5 inhibitors with their valuable effects on erection have provided a breakthrough in the treatment of erectile dysfunction and opened new fields of clinical application for this class of drugs. Oral PDE5 inhibitors have been demonstrated to possess many beneficial useful additional implications with acknowledged anti-inflammatory, antioxidant, immune response regulation, and antiapoptotic properties. These properties have been elucidated through the nitric oxide/soluble guanylyl cyclase/cyclic guanylate monophosphate pathway in addition to the emerged hemeoxygenase-1 enzyme as well as hydrogen sulfide pathways. These properties could support repurposing oral PDE5 inhibitors' potential adjuvant use in targeting different aspects of COVID-19 infection. Conclusion Oral PDE5 inhibitors retain several acknowledged off-labeled useful implications with anti-inflammatory, antioxidant, immune response regulation, and antiapoptotic properties. These properties may support repurposing oral PDE5 inhibitors' potential adjuvant use in the protocols combating COVID-19 manifestations. Mostafa T. Could Oral Phosphodiesterase 5 Inhibitors Have a Potential Adjuvant Role in Combating Coronavirus Disease 2019 Infection? Sex Med Rev 2021;9:15–22.

The Sexual Long COVID (SLC): Erectile Dysfunction as a Biomarker of Systemic Complications for COVID-19 Long Haulers

“…The benefits of these drugs do not end here: sildenafil, the first and most widely known PDE5i, also has anti-aggregation properties and inhibits neointimal hyperplasia through the cGMP-dependent protein kinase (cGK) pathway, thus preventing further vascular injury and thrombosis 110 , and has anti-inflammatory 111 , anti-apoptotic 112 and anti-oxidant 113 properties which could improve inflammatory status in the lungs. Therefore, PDE5i can potentially be beneficial for both erectile and pulmonary function in long COVID patients, as currently investigated by dedicated trials 114 , 115 , 116 .…”

Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections

“…Whether these agents should have antimicrobial effects is unclear since they do not enhance NO levels per se; nevertheless, both drugs have exhibited antimicrobial activity (Table 7) and are being tested in COVID-19 trials (Table 9). 102,103 Stimulation of endogenous nitric oxide-dependent nitric oxide production Endogenous NO production may also be stimulated externally. First, nasal breathing promotes the production of NO from the paranasal sinuses and this has bronchodilatory, vasodilatory and potential antimicrobial activities.…”

Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections

“…Whether these agents should have antimicrobial effects is unclear since they do not enhance NO levels per se; nevertheless, both drugs have exhibited antimicrobial activity (Table 7) and are being tested in COVID-19 trials (Table 9). 107,108 Stimulation of endogenous nitric oxide-dependent nitric oxide production Endogenous NO production may also be stimulated externally. First, nasal breathing promotes the production of NO from the paranasal sinuses and this has bronchodilatory, vasodilatory and potential antimicrobial activities.…”