Carvedilol and COVID-19: A Potential Role in Reducing Infectivity and Infection Severity of SARS-CoV-2

Abstract

Angiotensin-converting enzyme 2 (ACE 2) is expressed by several cells in the body, like the epithelial cells of the lungs and the blood vessels. It is a host receptor for severe acute respiratory syndrome coronavirus [SARS-CoV] and SARSCoV-2. 1 ACE inhibitors and angiotensin II type I receptor blockers (ARBs) cause an upregulation of ACE2. 2 Patients with hypertension and diabetes are at increased risk of COVID-19 infection. 2 This can possibly be because they are frequently treated with ACE inhibitors and ARBs, which increase the host receptor of the virus. 2 Carvedilol is a drug with vasodilating properties, initially designed for managing hypertension and coronary artery disease. Unlike ACE inhibitors that increase the expression of ACE 2, carvedilol decreases its expression. 3 This is why, ACE inhibitors or ARBs prescribed for hypertensive patients can be replaced by carvedilol during this pandemic. Moreover, not only patients on ACE inhibitors or ARBs can benefit from carvedilol. Since carvedilol decreases the expression of ACE, which is the COVID-19 host receptor, it can be useful for all COVID-19 patients.On the other hand, carvedilol can fight COVID-19 by another mechanism. Carvedilol has interleukin 6 (IL-6) suppressing properties. 4 Detectable serum SARS-CoV-2 viral load is closely associated with drastically elevated IL-6 level in critically ill COVID-19 patients. 5 So, carvedilol can be used to target IL-6, which plays a major role in the inflammatory cascade of COVID-19.In conclusion, we hypothesize that by downregulating ACE and by having anti-IL-6 properties, carvedilol has the potential to block 2 pathogenic pathways of COVID-19.

Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

“…Several drugs prescribed in the field of cardiovascular diseases were also found active in the CPE assay. These include Vorapaxar (reduces the incidence of thrombotic cardiovascular events or with peripheral arterial disease, a molecule proposed as potentially interesting for the treatment of COVID-19 patients 28 ), Carvedilol (treatment of heart failure, hypertension, a molecule also suggested in the literature as potentially beneficial for COVID-19 patients via several mechanisms of action 29 ) or Nicardipine (antihypertensive properties effective in the treatment of angina and coronary spasms).…”

Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

“…Several drugs prescribed in the field of cardiovascular diseases were also found active in the CPE assay. These include Vorapaxar (reduces the incidence of thrombotic cardiovascular events or with peripheral arterial disease, a molecule proposed as potentially interesting for the treatment of COVID-19 patients 43 ), Carvedilol (treatment of heart failure, hypertension, a molecule also suggested in the literature as potentially beneficial for COVID-19 patients via several mechanisms of action 44 ) or Nicardipine (antihypertensive properties effective in the treatment of angina and coronary spasms). Another very interesting compound is Bepridil, a long-acting calciumblocking agent with significant anti-anginal activity.…”

Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19

“…The antiviral activities of Glycyrrhizin have been extensively studied in the context of other human viruses and most notably, the drug was found to potently suppress replication of two clinical isolates of SARS-associated coronavirus in Vero cells ( Cinatl et al, 2003 ), and preliminarily, neutralize SARS-CoV-2 by inhibiting the viral main protease ( van de Sand et al, 2021 ). Further, Carvedilol and Acetaminophen have been reported to decrease the expression of ACE2 and serine protease TMPRSS2, respectively ( Zarubin et al, 2020 ; Skayem and Ayoub, 2020 ), both of which are required for SARS-CoV-2 entry into cells ( Hoffmann et al, 2020 ). Hence, drug combinations that simultaneously exert both anti-inflammatory and antiviral effects against SARS-CoV-2 may have the greatest potential to be effective in treating COVID-19.…”