The AI-Assisted Identification and Clinical Efficacy of Baricitinib in the Treatment of COVID-19

Abstract

During the current pandemic, the vast majority of COVID-19 patients experienced mild symptoms, but some had a potentially fatal aberrant hyperinflammatory immune reaction characterized by high levels of IL-6 and other cytokines. Modulation of this immune reaction has proven to be the only method of reducing mortality in severe and critical COVID-19. The anti-inflammatory drug baricitinib (Olumiant) has recently been strongly recommended by the WHO for use in COVID-19 patients because it reduces the risk of progressive disease and death. It is a Janus Kinase (JAK) 1/2 inhibitor approved for rheumatoid arthritis which was suggested in early 2020 as a treatment for COVID-19. In this review the AI-assisted identification of baricitinib, its antiviral and anti-inflammatory properties, and efficacy in clinical trials are discussed and compared with those of other immune modulators including glucocorticoids, IL-6 and IL-1 receptor blockers and other JAK inhibitors. Baricitinib inhibits both virus infection and cytokine signalling and is not only important for COVID-19 management but is “non-immunological”, and so should remain effective if new SARS-CoV-2 variants escape immune control. The repurposing of baricitinib is an example of how advanced artificial intelligence (AI) can quickly identify new drug candidates that have clinical benefit in previously unsuspected therapeutic areas.

COVID-19: A Comprehensive Review on Cardiovascular Alterations, Immunity, and Therapeutics in Older Adults

“…Baricitinib was approved by the FDA in May 2022 for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. The World Health Organization recommended its use for the treatment of COVID-19 patients because of its ability to reduce the risk of progressive disease and death [ 140 ]. Importantly, a study in elderly people (older than 70 years) demonstrated a reduction (18.5%) in the absolute mortality risk in the studied cohort [ 141 ].…”

Janus kinase inhibitors are potential therapeutics for amyotrophic lateral sclerosis

“…Baricitinib has also been taken for brief periods by over one million seriously ill hospitalised patients with COVID-19. In meta-analyses, few, if any, drug-induced serious adverse events were reported in this patient population; in contrast, the drug showed significant mortality benefits even when added to other treatments such as steroids and tocilizumab [ 177 ]. In addition, the incidence of secondary infections with COVID-19 was reduced by 50% by baricitinib in the ACTT-2 clinical trial [ 178 ].…”

The Potential of Anti-coronavirus Plant Secondary Metabolites in COVID-19 Drug Discovery as an Alternative to Repurposed Drugs: A Review

“…Vein thrombosis [30][31] Paxlovid (Nirmatrelvir-Ritonavir) Inhibition of viral replication Headache, diarrhea, vomiting dysgeusia [32] Molnupiravir (Lagevrio) Inhibition of virus multiplying Dizziness, rash, diarrhea, nausea [33][34] Kineret (anakinra) Inhibition of interleukin-1 (IL-1) receptor Reaction in injection site, enhancement of liver enzymes, hypertension [35][36] Gohibic (Vilobelimab) Vilobelimab as an antagonist od complement component 5a (C5-a) receptor, acts as anti-inflammatory agent Hypertension, pneumonia, pulmonary embolism, delirium, and sepsis [37] Prioritizing Potential Candidates for Anti-SARS-CoV-2 Drug Development and Discovery from Phytochemicals and Plant Secondary Metabolites…”

“…The repurposed antiviral drugs used to treat COVID-19 may provide protection against infection or speed up recovery, but all COVID-19 antiviral drugs currently on the market have drawbacks that may prevent their use by the general public [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. For example, remdesivir administration led to mild to moderate undesirable outcomes, including but not restricted to liver toxicity, queasiness, anemia, kidney impairment, low blood pressure, respiratory collapse, and constipation, among other things [38][39][40][41][42].…”