Scientific hypothesis and rational pharmacological for the use of sacubitril/valsartan in cardiac damage caused by COVID-19

Abstract

On March 11, 2020 the World Health Organization (WHO) declared the state of global pandemic caused by the new SARS-CoV-2 (COVID-19). To date, no antivirals directed against SARS-CoV-2 or effective vaccines to combat the viral infection are available. Severe acute respiratory syndrome caused by SARS-CoV-2 is treated empirically with antivirals, anti-inflammatory, anticoagulants. The approval of an effective vaccine still takes time. In this state, it may be useful to find new therapeutic solutions from drugs already on the market. Recent hypotheses suggest that the use of AT-1 receptor antagonists (ARB) in combination with neprilisin inhibitors (NEPi) could indirectly provide clinical benefits to patients with SARS-CoV-2 and cardiac involvement. In this article we investigate and describe a possible innovative pharmacological approach for the treatment of the most severe stages of COVID-19 infection.

Keywords: Cardiology; Covid-19; Cytokine; Neprilisin; Sacubitril; Sars-CoV-2.

Fig. 1

The proinflammatory cytokine TNF-alpha can induce apoptosis of cardiac myocytics inducing cardiac damage.

Fig. 2

Pro-inflammatory cytokine IL-1 mediates inotropic negative effect and contractile cardiac dysfunction.

Fig. 3

Mechanism of action: Sacubitril/valsartan has the mechanism of action of neprilisin inhibitor and angiotensin II receptor blocker type-1 (AT1). The complementary cardiovascular benefits of sacubitril/valsartan are attributed to the increase in neprilisin-degraded peptides and the simultaneous inhibition of the effects of angiotensin II. Natriuretic peptides exert their effects through the activation of membrane bound receptors coupled to the enzyme guanylyl cyclase, causing an increase in concentrations of the second messenger, cyclic guanosine monophosphate (cGMP), which can lead to vasodilation, natriuresis and diuresis, increased glomerular filtration rate and renal blood flow, inhibition of renin and aldosterone release, reduction of sympathetic activity and antihypertrophic/antifibrotic effects.