Artemisinin in the quantity of 125 mg on the first day and 62.5 mg for the next 6 days, with piperaquine in the quantity of 750 mg for the first day and 375 mg for the next 6 days almost halved the time to reach undetectable SARS-CoV-2 level vs. the control group, according to the clinical study disclosed in Guoming Li et al., “Safety and efficacy of artemisinin-piperaquine for treatment of COVID-19: an open-label, non-randomised and controlled trial,” International Journal of Antimicrobial Agents, January 2021, 57(1), 106216, https://doi.org/10.1016/j.ijantimicag.2020.106216, JIF 15.441 (top 3% journals in Pharmacology & Pharmacy).
Artemisinin family drugs are potent anti-malarial agents with high efficacy and low toxicity. Besides the outstanding antimalarial activity, artemisinin and its derivatives are also able to regulate various aspects of immune responses, such as macrophage activation, T cell activation and proliferation, T cell subsets differentiation (Th1, Th17, Treg). Furthermore, the recent finding that artesunate can regulate GC B cells highlights artesunate's role in humoral immune response, according to Lifei Hou et al., “Immune suppressive properties of artemisinin family drugs,” Pharmacology and Therapeutics, 166 (2016), pp. 123-127, https://doi.org/10.1016/j.pharmthera.2016.07.002, JIF (top 4% journals in Pharmacology & Pharmacy / top 3% journals in Pharmacology & Pharmacy in 2016).
This article reviews the data-based immunomodulatory effects of artemisinins on different immune cells including neutrophils, macrophages, splenocytes, T and B cells in conjunction with their therapeutic prospective with regard to inflammation, autoimmunity and delayed-type hypersensitivity, according to Lubna Shakir et al., “Artemisinins and immune system,” European Journal of Pharmacology, 668 (2011), pp. 6-14, https://doi.org/10.1016/j.ejphar.2011.06.044, JIF (top 26% journals in Pharmacology & Pharmacy / top 40% journals in Pharmacology & Pharmacy in 2011).
Artemisinin and its analogs, such as dihydroartemisinin, artemether, artesunate, artemiside, artemisone, and arteether, possess not only potent antimalarial activity but also anti-viral, antifungal, anticancer, and anti-inflammatory properties. Artemisinins have an immunomodulatory effect on diverse components of the immune system through affecting various immune cells responses. They suppress the secretion of cytokines and related signaling pathway, induce decrease in neutrophils, reduce macrophage functional responses, and inhibit lymphocyte proliferation and maintenance. Also, artemisinins affect signaling pathway cascades, including those for TLR, PLCγ, PKC, Akt, MAPK, Wnt, STATs, NF-κB, and Nrf2/ARE, according to Wenbo Yao et al. “Immunomodulation of artemisinin and its derivatives,” Science Bulletin, 61 (2016), pp. 1399-1406, https://doi.org/10.1007/s11434-016-1105-z, JIF (top 7% journals in multidisciplinary sciences / top 18% journals in multidisciplinary sciences in 2016).
As demonstrated in recent years, the class of artemisinin-type compounds has activity against malaria, cancer cells, and schistosomiasis. Interestingly, the bioactivity of artemisinin and its semisynthetic derivative artesunate is even broader and includes the inhibition of certain viruses, such as human cytomegalovirus and other members of the Herpesviridae family (e.g., herpes simplex virus type 1 and Epstein-Barr virus), hepatitis B virus, hepatitis C virus, and bovine viral diarrhea virus, according to Thomas Efferth et al., “The antiviral activities of artemisinin and artesunate,” Clinical Infectious Diseases, 47 (2008), pp. 804-811, https://doi.org/10.1086/591195, JIF (top 5% journals in Immunology / top 10% journals in Immunology in 2008, top 7% journals in Infectious Diseases / top 4% journals in Infectious Diseases in 2008, and top 5% journals in Microbiology / top 7% journals in Microbiology in 2008).