High Blood Pressure & Cardiovascular Prevention | 2021
Repurposing Cardio-Metabolic Drugs to Fight Covid19
Abstract
Since November 2019, healthcare systems around the world had to face the consequences of the pandemic caused by the Sars-CoV-2 virus. This virus is a positive-sense singlestranded RNA virus classified as coronavirus. Two previous epidemics caused by coronaviruses developed in 2000s, but had been confined to specific regions of the world. On the contrary, the disease associated with Sars-Cov-2 infection, known as Covid19, due to its very high contagiousness, has taken on the measure of a pandemic. To date, more than two hundred million cases are confirmed, with over four million deaths globally [1]. Covid19 mostly manifests with interstitial pneumonia, even though it can affect heart and central nervous system as well. Although the pathophysiology of the clinical manifestations of Covid19 is not yet completely known, it has been shown that the entry of Sars-CoV-2 into cells is mediated by angiotensin-converting enzyme 2 (ACE2), expressed also in pulmonary epithelium [2]. After that, symptoms and the severity of Covid19 depend on the virus replication but also on the individual s immune response, often establishing an immune/inflammatory storm leading to tissue damage that can have severe prognosis [2, 3]. In parallel with the progressive knowledge about the mechanisms of Sars-CoV-2 infection and the pathophysiology of Covid19, the search for possible therapeutic targets for drugs aimed at treating patients affected by Covid19 has been developed. However, the design of new drugs requires time and investments. Indeed, the cost of a new drug is estimated to more than a billion dollars extending for a period of 10–15 years [4] with a success rate of only 2.01% [5]. For this reason, most of the efforts have been lately used in a titanic way to develop vaccines to stem the spread of the virus and hopefully eradicate it. Currently four vaccines (Tozinameran/BNT162b2/Comirnaty by Pfizer/BioNTech), mRNA-1273 by Moderna), AZD1222/Covishield by University of Oxford/AstraZeneca and Ad26.COV2.S/JNJ78436735 by Janssen Vaccines and Prevention) have been developed in western countries and more than 5 billion doses have already been administered worldwide [1]. However, the search for drugs useful in treating Covid19 in people already affected is not of secondary importance. This is particularly crucial if we consider the likely development and spread of new variants of the virus, the percentage of people not able to be immunized globally due to the presence of comorbidities and the evidence that currently only 33% of the world population have received at least one doses. In particular, populous countries with the lower incomes, such as India, do not have free access to vaccines, with only 1.6% of people in low-income countries have received at least one dose [6]. Although several drugs are under active investigation, there are currently no effective drugs against SARS-CoV-2 infection [7]. The most used therapeutic schemes consist of glucocorticoids and anticoagulants as the immune storm as well as the damage of the endothelium and thrombotic processes seem critical in the evolution of the infection and prognosis. Data from the large RECOVERY trial, a controlled open-label trial involving more than 6000 patients, have shown that in patients hospitalized with Covid19, the use of dexamethasone resulted in lower 28-day mortality among those patients on respiratory support [8]. Since the beginning of the pandemic, the repurpose of drugs, which is the process of identifying new uses for approved drugs, has been suggested for the treatment of Covid19, due to the enormous need for health sources and high economic burden of the pandemic. Based on viral pathogenesis and pharmacodynamics, many agents might be repurposed [9]. Drug repurposing is based on two principles. * Allegra Battistoni [email protected]