Abstract
The emergence of the COVID-19 pandemic has mandated the instant (re)search for potential drug candidates. In response to the unprecedented situation, it was recognized early that repurposing of available drugs in the market could timely save lives, by skipping the lengthy phases of preclinical and initial safety studies. BenevolentAI’s large knowledge graph repository of structured medical information suggested baricitinib, a Janus-associated kinase inhibitor, as a potential repurposed medicine with a dual mechanism; hindering SARS-CoV2 entry and combatting the cytokine storm; the leading cause of mortality in COVID-19. However, the recently-published Adaptive COVID-19 Treatment Trial-2 (ACTT-2) positioned baricitinib only in combination with remdesivir for treatment of a specific category of COVID-19 patients, whereas the drug is not recommended to be used alone except in clinical trials. The increased pace of data output in all life sciences fields has changed our understanding of data processing and manipulation. For the purpose of drug design, development, or repurposing, the integration of different disciplines of life sciences is highly recommended to achieve the ultimate benefit of using new technologies to mine BIG data, however, the final say remains to be concluded after the drug is used in clinical practice. This review demonstrates different bioinformatics, chemical, pharmacological, and clinical aspects of baricitinib to highlight the repurposing journey of the drug and evaluates its placement in the current guidelines for COVID-19 treatment.
Highlights
Our transcriptomic analysis of baricitinib-treated model revealed a significant downregulation of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in patients treated with baricitinib (Figure regulation of ACE2 and TMPRSS2 in patients treated with baricitinib (Figure 3)
The first key study was published by Stebbing et al, 2020 who showed that baricitinib inhibited signalling of COVID-19-related cytokines in an in-vitro model
In response to the unprecedented COVID-19 pandemic, a plethora of medications has been repurposed in an attempt to combat the infection and its sequelae
Summary
Drug repurposing is currently the most significant strategy followed in the treatment guidelines of the unprecedented COVID-19 pandemic. As repurposed drugs are already in clinical use, there is relative confidence in their safety, at least when used for their original purpose [2]. Repurposing dictates enrollment of patients in clinical trials for the specific new indication, in this case, treatment of COVID-19. A subgroup of patients with severe respiratory disease due to COVID-19 may feature a “cytokine release syndrome”, or “cytokine storm” (CS), which is linked to increased activation of. This review will discuss different perspectives of barictinib repurposing in COVID-19 treatment; including bioinformatics analysis, using relevant datasets; chemistry, demonstrating assessment of the structural activity relationship; pharmacology, reporting key kinetics and clinical use of baricitinib. The outline of the completed and ongoing clinical trials on this medication will be discussed
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