Abstract
BackgroundDriven by the COVID-19 pandemic and the dire need to discover an antiviral drug, we explored the landscape of the SARS-CoV-2 biomedical publications to identify potential treatments.ObjectiveThe aims of this study are to identify off-label drugs that may have benefits for the coronavirus disease pandemic, present a novel ranking algorithm called CovidX to recommend existing drugs for potential repurposing, and validate the literature-based outcome with drug knowledge available in clinical trials.MethodsTo achieve such objectives, we applied natural language processing techniques to identify drugs and linked entities (eg, disease, gene, protein, chemical compounds). When such entities are linked, they form a map that can be further explored using network science tools. The CovidX algorithm was based upon a notion that we called “diversity.” A diversity score for a given drug was calculated by measuring how “diverse” a drug is calculated using various biological entities (regardless of the cardinality of actual instances in each category). The algorithm validates the ranking and awards those drugs that are currently being investigated in open clinical trials. The rationale behind the open clinical trial is to provide a validating mechanism of the PubMed results. This ensures providing up to date evidence of the fast development of this disease.ResultsFrom the analyzed biomedical literature, the algorithm identified 30 possible drug candidates for repurposing, ranked them accordingly, and validated the ranking outcomes against evidence from clinical trials. The top 10 candidates according to our algorithm are hydroxychloroquine, azithromycin, chloroquine, ritonavir, losartan, remdesivir, favipiravir, methylprednisolone, rapamycin, and tilorone dihydrochloride.ConclusionsThe ranking shows both consistency and promise in identifying drugs that can be repurposed. We believe, however, the full treatment to be a multifaceted, adjuvant approach where multiple drugs may need to be taken at the same time.
Highlights
In December 2019, the first known cases of the coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were identified in humans in Wuhan, China
It is speculated that SARS-CoV-2 enters the body by binding to the angiotensin-converting enzyme 2 (ACE2) coreceptors in a host cell, which are found in tissues of the lung, heart, kidney, brain, and gastrointestinal system
The actual ACE2 enzyme is involved with the renin-angiotensin-aldosterone system (RAAS), where it breaks down angiotensin II (ANG II) and generates angiotensin 1-7, thereby decreasing blood pressure in the body [35]
Summary
Background In December 2019, the first known cases of the coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were identified in humans in Wuhan, China. With no immunity among humans, at the time of this writing, SARS-CoV-2 has infected over 4.5 million individuals and killed over 300,000 individuals worldwide with the potential for many more fatalities without a known cure or vaccination [3]. Studies have shown that cardiac injury occurred in up to 28% of patients hospitalized with a SARS-CoV-2 infection [4], which can increase the risk of death later on. The systemic inflammatory response that occurs in severe SARS-CoV-2 infection may result in hypoxemia and increased cardiac demand on an already taxed cardiovascular system. Driven by the COVID-19 pandemic and the dire need to discover an antiviral drug, we explored the landscape of the SARS-CoV-2 biomedical publications to identify potential treatments
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