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Covid-19, drugs to get ahead

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WE ARE NOT TALKING ABOUT VACCINES, but about some drugs that could be adapted to manage the early stage of the disease, avoiding its progression and therefore hospitalization and possible intensive therapy.

This result was achieved by researchers from the VA Boston Healthcare System, the University of Cambridge, the European Institute of Bioinformatics of EMBL (EMBL-EBI) and the Italian Institute of Technology (IIT) with a research published in the journal Nature Medicines

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By comparing large-scale genetic analyzes with available drug data, the team has identified some human protein-coding genes involved in the progression of Covid-19, which are also targets of already approved drugs. Taking the latter after the diagnosis of the disease, before patients need to be hospitalized, could help minimize symptoms and reduce numbers in ICUs.

The IIT team saw Stefano Gustincich, Associate Director for Technologies for Life Sciences and Director of the Central RNA Laboratory, Gian Gaetano Tartaglia, Head of the RNA System Biology Lab. Claudia Giambartolomei, researcher and one of the first authors of the study, to whom we asked how the research was born.

“Early last summer we began working with colleagues at the VA Boston Healthcare System and those at EMBL-EBI to try to figure out which drugs to prioritize for clinical trials. In Boston they have an extremely rich database on veterans, with a lot of data on individuals hospitalized for Covid 19 and therefore we have also moved forward together with the University of Cambridge and the European Institute of Bioinformatics, which has the ChEMBL bioactivity database on proteins under development in clinical trials “.

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Through computational analysis methods, 1,263 genes, called “actionable druggable genomes,” were identified, then the researchers studied the prevalence of variants of these genes within two large genetic data samples from VA’s Million Veteran Program and COVID-19. Host Genetics Initiative. The analysis involved 7,554 hospitalized COVID-19 patients and more than a million controls. Data on hospitalized patients and those on controls are important because they provide information before the disease becomes severe, to prevent hospitalization. This approach provided genetic evidence for drugs that target two proteins: ACE2 and IFNAR2.

“Genetic analyzes are fundamental – adds Dr. Giambartolomei – because it is proven that they are twice as successful when carried out in a clinical trial. The drugs for ACE 2 are in clinical development, in phase 2, not yet approved for no disease. APN01 was, for example, initially developed for SARS in 2003, and evaluated in clinical trials to reduce inflammation. APN 01 basically binds to the receptor blocking the virus entry into the human cell and regulates a hormonal response that helps prevent inflammation “.

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“It is very important – he continues – to understand which drugs, already approved, can be readapted, because many of those on the market target proteins, these proteins are encoded by genes and by looking at the variants contained in the genes we can anticipate the pharmacological effect. In practice, by observing the variants present in hospitalized cases we emulate the effect of a drug “.

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At the beginning, the available data were only related to people already hospitalized, but now Covid patients can be identified and treated before they progress to more severe forms of the disease, thus also avoiding hospitalization and intensive care.

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