Repurposing Anti-Malaria Phytomedicine Artemisinin as a COVID-19 Drug

Abstract

Artemisinin is an anti-inflammatory phytomedicine with broad-spectrum antiviral activity. Artemisinin and its antimalarial properties were discovered by the Chinese scientist Tu Youyu, who became one of the laureates of the 2015 Nobel Prize in Physiology or Medicine for this breakthrough in tropical medicine. It is a commonly used anti-malaria drug. Artemisinin has recently been repurposed as a potential COVID-19 drug. Its documented anti-SARS-CoV-2 activity has been attributed to its ability to inhibit spike-protein mediated and TGF-β-dependent early steps in the infection process as well as its ability to disrupt the post-entry intracellular events of the SARS-CoV-2 infection cycle required for viral replication. In addition, Artemisinin has anti-inflammatory activity and reduces the systemic levels of inflammatory cytokines that contribute to cytokine storm and inflammatory organ injury in high-risk COVID-19 patients. We postulate that Artemisinin may prevent the worsening of the health condition of patients with mild-moderate COVID-19 when administered early in the course of their disease.

Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma

“…Notably, MM cells have upregulated expression of TGF-β-activated kinase-1 (TAK1), and inhibiting TAK1 has been shown to significantly impair the growth and survival of MM cells [ 75 ]. Therefore, targeting TGF-β signaling with an RNA therapeutic such as OT101, the TGF-β targeting anti-inflammatory platforms such as RJX [ 76 ] or ArtiVeda [ 77 , 78 ] or a small molecule inhibitor such as galunisertib could contribute to sustained anti-tumor immunity and PD-1/PD-L1 responsiveness by lifting TGF-β-mediated immunosuppression.…”

Sinapic Acid Suppresses SARS CoV-2 Replication by Targeting Its Envelope Protein

“…Later, artemisinin and its congeners also demonstrated a significant in vitro anti-SARS CoV-2 inhibitory activity. Additionally, it was reported to contribute to a faster recovery of COVID-19 patients [13,14]. Both ivermectin and artemisinin were suggested to exert their antiviral activity by blocking the viral entry inside the host cells via several mechanisms [10][11][12][13][14].…”

“…Additionally, it was reported to contribute to a faster recovery of COVID-19 patients [13,14]. Both ivermectin and artemisinin were suggested to exert their antiviral activity by blocking the viral entry inside the host cells via several mechanisms [10][11][12][13][14]. Recently, a group of plant-derived phenolic compounds has shown potent in vitro anti-SARS CoV-2 activity via targeting the viral main protease [15,16].…”

Bioguided Isolation of Cyclopenin Analogues as Potential SARS-CoV-2 Mpro Inhibitors from Penicillium citrinum TDPEF34

“…The following conditions were used: capillary voltage of 45 V, capillary temperature of 260 • C, auxiliary gas flow rate of 10-20 arbitrary units, sheath gas flow rate of 40-50 arbitrary units, spray voltage of 4.5 kV, and mass range of 100-2000 amu (maximal resolution of 30,000). Structure characterizations of all compounds were based on 1 H-NMR, 13 C-NMR, COSY, HSQC, and HMBC data obtained using Bruker Avance III spectrometer 600 MHz (Bruker UK Ltd. Coventry, UK). Optical rotations were recorded using a PerkinElmer 343 polarimeter (PerkinElmer Ltd., Buckinghamshire, UK).…”

“…The isolated compounds included a series of benzodiazepine alkaloids analogues; cyclopeptin (1) which were isolated as two conformers, A and B, in a 4:6 ratio at room temperature which coalesced into a single conformer at 85 • C [21]: dehydrocyclopeptin (2) [22,23]; cyclopenin (3) [23][24][25]; cyclopeniol (4) [23][24][25]; two hydroxyquinolone alkaloids viridicatins analogues, viridicatol (5) [26,27] and 3-O-methylviridicatin (6) [28,29]; the alkaloid peniamidone A (7) [30]; a scytalone analogue, E-4-hydroxy-6-deoxyscytalone (8) [31]; pseurotin A (9) [32][33][34]; fructigenine A (10) [35], and finally penipratynolene (11) [36]. All compounds were fully characterized by comparing their HRMS, 1 H, 13 C and HSQC spectral data and optical rotation data with the reported literature (supplementary data, Figures S1-S54). All substructures' connectivities were further confirmed through COSY and HMBC correlations.…”