- Janus kinase (JAK) inhibitors reduce inflammation by inhibiting cytokine signaling. Their potential role in managing the cytokine storm leading to acute lung injury, acute respiratory distress syndrome and death have been evoked. 1,2
- Their biggest concern is that the inhibition of a wide variety of inflammatory cytokines includes INF-a, which is important in fighting virus.1
- Meanwhile, 2019-nCoV is thought to infect AT2 lung cells through ACE2 receptor-mediated endocytosis.
- AP2-associated protein kinase 1 (AAK1) is a regulator of endocytosis.
- Disruption of AAK1 might interrupt the passage of the virus into cells.2
- While all JAK inhibitors have anti-inflammatory effects, Baricitinib (a JAK inhibitor drug used in rheumatoid arthritis) has an additional antiviral effect because of its high affinity binding AAK1 and also by binding the G-associated kinase, another endocytosis regulator. Its plasma concentration on relatively safe therapeutic dosing (2 or 4 mg daily) is sufficient to inhibit AAK1, making it a good candidate to be trialled in patients with COVID-19.2
As of April 7 2020, clinical trials are recruiting patients to investigate the efficacy of baricitinib, ruxolitinib, jakotinib and tofacitinib.
These statements come from two sources. The first is from a review based on the perspective of Chinese clinical immunologists in regard to the clinical and immunological characteristics of severe patients. They summarize the current evidence and share their experience with anti-inflammatory treatment of COVID-19.1
The second source is from an editorial published in the lancet regarding the rationale behind the potential treatment with Baricitinib. The authors also stated that sunitinib and erlotinib (oncology drugs) have shown their viral infection inhibition through the inhibition of AAK1 in the past. However, high doses were needed to reach effective inhibition and these compounds included serious side-effects.2
- Zhang W, Zhao Y, Zhang F, et al (March 25 2020). The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clinical Immunology. https://doi.org/10.1016/j.clim.2020.108393
- Richardson P, Griffin I, Tucker C et al (February 3 2020). Baricitinib as potential treatment for 2019-nCoV acute respiratory disease, Lancet. https://doi.org/10.1016/S0140-6736(20)30304-4