Coronavirus disease 2019 is caused by SARS-CoV-2 and is more severe in the elderly, racial minorities, and those with comorbidities such as hypertension and diabetes. These pathologies are often controlled with medications involving the renin–angiotensin–aldosterone system (RAAS). RAAS is an endocrine system involved in maintaining blood pressure and blood volume through components of the system. SARS-CoV-2 enters the cells through ACE2, a membrane-bound protein related to RAAS. Therefore, the use of RAAS inhibitors could worsen the severity of COVID-19’s symptoms, especially amongst those with pre-existing comorbidities. Although a vaccine is currently available to prevent and reduce the symptom severity of COVID-19, other options, such as nitric oxide and hydrogen sulfide, may also have utility to prevent and treat this virus.

According to the World Health Organization (WHO), the prevalence of obesity across the globe has nearly tripled since 1975, with 39 million children under the age of 5 being overweight or obese in 2020. Obesity is the most common risk factor for developing type 2diabetes (T2D), which may lead to elevated serum triglycerides, hypertension, and insulin resistance. In the pathogenesis of T2D, there is a reduction in nitric oxide (NO) bioavailability. Restoration of NO levels has been associated with many favorable metabolic effects in T2D. Drugs that potentiate NO levels may have a role in improving T2D-associated adverse effects. Current medications approved for use in the management of T2D include biguanides, thiazolidinediones, sulfonylureas, meglitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP- 1) receptor agonists, alpha-glucosidase inhibitors, and sodium-glucose co-transporter 2 (SGLT2) inhibitors. These drugs mitigate the many adverse effects associated with T2D. This chapter discusses these classes of drugs, examines their mechanism of action, and presents evidence that these drugs directly or indirectly modulate NO levels.

Nitric oxide (NO), a gaseous free radical, is a key signaling molecule in the different phases of the normal wound healing process. The beneficial effects of NO in wound healing are related to its antibacterial properties, regulation of inflammatory response, stimulation of proliferation and differentiation of keratinocytes and fibroblasts, and promotion of angiogenesis and collagen deposition. NO deficiency is an important mechanism responsible for poor healing in diabetic wounds. In this chapter, the function of NO in diabetic wound healing and the possible therapeutic significance of NO in the treatment of diabetic wounds are discussed. Current knowledge supports this notion that NO-based intervention is a promising therapeutic approach for diabetic wound healing.