Abstract
From January 2020, COVID-19 is spreading around the world producing serious respiratory symptoms in infected patients that in some cases can be complicated by the severe acute respiratory syndrome, sepsis and septic shock, multiorgan failure, including acute kidney injury and cardiac injury. Cost and time efficient approaches to reduce the burthen of the disease are needed. To find potential COVID-19 treatments among the whole arsenal of existing drugs, we combined system biology and artificial intelligence-based approaches. The drug combination of pirfenidone and melatonin has been identified as a candidate treatment that may contribute to reduce the virus infection. Starting from different drug targets the effect of the drugs converges on human proteins with a known role in SARS-CoV-2 infection cycle. Simultaneously, GUILDify v2.0 web server has been used as an alternative method to corroborate the effect of pirfenidone and melatonin against the infection of SARS-CoV-2. We have also predicted a potential therapeutic effect of the drug combination over the respiratory associated pathology, thus tackling at the same time two important issues in COVID-19. These evidences, together with the fact that from a medical point of view both drugs are considered safe and can be combined with the current standard of care treatments for COVID-19 makes this combination very attractive for treating patients at stage II, non-severe symptomatic patients with the presence of virus and those patients who are at risk of developing severe pulmonary complications.
Highlights
The pandemic disease COVID-19 caused by Severe acute respiratory syndrome (SARS)-CoV-2 is an active infection that has affected at least hundreds of thousands of individuals around the world
Human key molecular enclaves in COVID-19 that could be good target areas for treatment have been identified through manual curation of scientific publications and gene expression analysis, describing molecularly aspects of the virus infection process from the host perspective and aspects related with the respiratory problems associated to the infection
1) ‘Coronavirus-host interaction set’ is composed of human proteins with a relevant role in SARS-CoV-2 infection process. This set of proteins has been obtained from a bibliographic revision and it is composed of proteins that potentially interact with SARS-CoV-2: TMPRSS2 [37], ACE2 [37], GRP78 [38], Furin [39], CD147 [40]
Summary
The pandemic disease COVID-19 caused by SARS-CoV-2 is an active infection that has affected at least hundreds of thousands of individuals around the world. COVID-19 typically causes flu-like symptoms including fever and cough. 20% of the patients develop respiratory complications such as pneumonia, with chest tightness, chest pain, and shortness of breath [2]. No specific treatment has been approved for COVID-19. Standard treatments focus on the symptoms, such as pain relievers (paracetamol or acetaminophen) and breathing support (mechanical ventilation) for patients with severe infection. Other repurposed therapies aiming at reducing viral load, spread or protecting the host machinery are currently being tested experimentally in more than 600 clinical trials, involving medicines such as: human immunoglobulin, interferons, chloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines [3]. Remdesivir, has shown encouraging results in a clinical trial, pointing that it is possible to block the virus using drugs [4]
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