Approach of utilizing Artemisia herbs to treat covid-19

Ben-Nasr, Hmed; Badraoui, Riadh

doi:10.1590/s2175-97902022e20345

Abstract

Huge plethora of studies pointed out the importance of several Artemisia herb molecules as treatment for many diseases. Among these natural substances, some molecules are known to counteract fever, inflammation, blood clotting and oxidative stress. Furthermore, they are dotted with activities against different strains of viruses including the SARS-coronaviruses. For these beneficial properties, these medicinal herbs are deemed as a potential candidate for covid-19 pandemic.

Keywords: Artemisia; Therapy; Potential; Covid-19

INTRODUCTION

The emergent SARS-CoV-2 belongs to the Coronaviridae family that causes severe acute respiratory syndrome with occasional pandemic features. The infection may lead to the coronavirus disease 2019 (covid-19), which manifests through fever, cough, nasal congestion, shortness of breath, loss of smell, headache and fatigue, among other symptoms. The progression of the pathology includes a harsh alveolar inflammation with the formation of a hyaline membrane. Vascular blood clots obtruding the exchange of respiratory gazes at the air-alveoli interface, in addition to lungs’ epithelial cell damages leading to fatality due to acute respiratory distress syndrome (Badraoui et al., 2020a; Gonzalez, 2020; Yuki, Fujiogi, Koutsogiannaski, 2020; Vetter, Eckerle, Kaiser, 2020). Yet, the medical care focuses on symptomatic therapy such as anti-inflammatory, antipyretics and mechanically assisted respiration. The severity of the disease is estimated dependently on the absence/presence of peculiar symptoms like the corporal temperature surpassing a threshold of 39°C and ansomia, thus the need for hospitalization (Wu et al., 2020a; Wu et al., 2020b; Badraoui et al., 2020a). Because of the lack of specific and effective conventional drugs to eliminate covid-19, great efforts are spent for such concern.

Along the human history, medicinal herbs have been of great interest in treating various diseases (Pereira et al., 2018; Badraoui et al., 2020b; Akacha et al., 2020). It has been reported that five species of the Artemisia genus (A. maritima, A. fragrans, A. macrocephala, A. scoparia and A. vulgaris) are already used by the Pakistan population to treat respiratory disorders. In such issue, Artemisia genus (from the Asteraceae family) is dotted with a large array of beneficial effects on health, and might be a potential candidate against covid-19 due to the major component namely artemesinin.

ANTIVIRAL POTENTIAL OF ARTEMISIA HERBS

Artemisia herbs contain hundreds of bioactive molecules including artemisinin and its derivatives that were effectively used to counteract malaria (Bora, Sharma, 2011; Kursat et al., 2015; Lis, Kowal, 2015; Nigam et al., 2019). These substances were actually reported to be potentially effective against several health problems (Kursat et al., 2015; Saoudi et al., 2017; Saoudi et al., 2021). Interestingly, the screening of Artemisia extracts proved that many derivatives such as artemisinin, kaempferol and rutin, and whole aerial parts extracts of Artemisia species exert virucidal effects against diverse types of viruses, including coronaviruses (Arbab et al., 2017; Brochot et al., 2017; Cheng et al., 2004; D’Alessandro et al., 2020; Han et al., 2015; Ivanescu, Miron, Corciova, 2015; Kim, Jeon, Ko, 2001; Lai et al., 2007; Li et al., 2005; Lubbe et al., 2012; Ma, Nakamura, Hattori, 2001; McCutcheon et al., 1995; Mitrocotsa et al., 2000; Romero et al., 2006; Sinico et al., 2005). The mechanism of action of these substances involves the inhibition of the virus attachment to its targeted cell, the expression of its proteins or its replication (Calderone et al., 1998; Efferth et al., 2008; Efferth, 2018; Wang et al., 2017). Some molecules, such as sterols, do prevent the targeted cell membrane lysis that is essential to the virus penetration (Abidi Ali Khan et al., 1991; Badraoui et al., 2021; Siddiqui et al., 2020). Other extracts restricted the horizontal cell to cell infection (Karamoddini et al., 2011; Saddi et al., 2007) and might be beneficial in covid-19 recovery, due to the antipyretic activity (Dib, Al Alaoui-Fares, 2019). In an animal experimental model, Shin (2017) proved that the oral intake of Artemisia agryi tea infusion improves the lungs’ inflammation induced by lipopolysaccharide. This effect was accompanied with a relevant reduction in inflammatory markers in bronchial fluid (Shin et al., 2017). Bora and Sharma (2011) reported that the anti-inflammatory process by the plant metabolites could prevent the subsequent formation of the haylin layers, which disrupts the gaseous exchange in the alveolar-capillary membrane. In an experimental model, Kim (2005) showed that an extract from A. capillaris exerts a potent inhibitory effect on the production of inflammatory mediators such as nitric oxide and prostaglandin E2. Accordingly, other species from Artemisia genus showed similar effects by modulating inflammation and the immune response (Krebs, Omer, Omer, 2010; Messaoudene et al., 2011; Yoon et al., 2010). They also protected pulmonary epithelial cells through the inhibition of the oxidative stress process (Bora, Sharma, 2011). According to Lai and his colleagues (2007) the essential oil of A. arborescens facilitates the antiviral drug absorption and subsequentlyameliorates the conventional therapy. Several investigations proved the presence of anticoagulant molecules in Artemisia (Lv, Li, Zhang, 2017; Ryu et al., 2013; Shahriyary, Yazdanprast, 2009; Wang et al., 2011) that might counteract the covid-19 induced coagulopathy (Giannis, Ziogas, Gianni, 2020) and improve the blood-alveolar exchange of respiratory gazes (Figure 1). As part of our project devoted to the effectiveness and safety of the Tunisian medicinal herbarium, the usage of Artemisia campestris leaves by local the population to treat acute bronchitis was considered. In fact, we conducted a pilot-phase I clinical trial (from December 2018 to February 2019) in order to evaluate its effectiveness and safety. For this end, acute bronchitis’ patients who were habituated to use A. campestris were treated either by oral administration of the infusion of the plant or the inhalation (snuffing) of 50 mg of its finely powdered leaves, as adjunct to conventional therapy. The Voucher specimen number of the used A. campestris is Bk11/96 and deposited in the Herbarium of the Institut des Regions Arides in Medenine, Tunisia. The phytochemical analysis of the plant, as assessed by mass spectrometric chromatography showed promising chemical compounds with potential health benefit (Akrout et al., 2001; Saoudi et al., 2017). Our results demonstrated that Artemisia campestris improves the wound healing of acute bronchitis, irrespectively of its viral or microbial origin. In fact, acutely diseased patients showed a relevant decrease in their bronchitis scaling score (BSS) following the intake of the infusion of 2 g of A. campestris leaves or the inhalation of 50 mg of its fine powder, twice daily for three successive days in comparison to placebo patients (who did not received the Artemisia treatment). The herb treatment significantly reduced the corporal temperature, blood C-reactive protein (CRP) content and the severity of respiratory distress symptoms, including dyspnea and cough. For example, the CRP concentration decreased from 28.75 ± 35.35 mg×L^-1 and 28.03 ± 52.08 mg×L^-1 to 7.74 ± 5.51 mg×L^-1, and 10.81 ± 13.28 mg×L^-1 respectively after the oral intake or the inhalation of A. campestris. However, there was substantial increase in CRP, from 16.20 ± 15.00 mg×mL^-1 to 19.57 ± 35.92 mg×mL^-1, in placebo. A complete resolution of cough was observed in 70%, 60% and 50%, respectively in patients treated by the herb product inhalation, or infusion, and placebo (unpublished data). Seemingly, the oral intake of Artemisia plants’ tea-infusion is much common throughout the world, but some studies reported also its use through the inhalation of its (Braithwaite, Van Vuuren, Vijoen, 2008; Yang et al., 2014). The induced phyto-therapy of the bronchitis might involve a bactericidal (Yang, Hu, Feng, 2015) and virucidal mechanisms (Arbab et al., 2017; Calderone et al., 1998; Efferth et al., 2008; Effert, 2018). In addition, the utilization of A. campestris by the two routes was almost safe and did not present any toxic feature.

FIGURE 1
Potential mode of action of Artemisia herbs’ extract in curing covid-19. Artemisia herbs contain several compounds with antiviral activities and are sought as potential candidate to treat covid-19. These substances might inhibit viruses’ replication, intracellular penetrance and inter-cells viral transmission. They also protect epithelial cells from the oxidative stress induced damages and prevent blood clotting in the vascular bed and the hyaline membrane formation which layout the gases’ exchange-interface through their anti-inflammatory process. Furthermore, some Artemisia chemicals might facilitate antiviral drugs cellular absorption and ameliorate their curative effects.

Currently, many herbal molecules are being investigated for their potential to relieve the acute respiratory syndrome induced by the SARS-CoV-2. They are shown to inhibit the entry of the virus to the host cell, and its proteases that determine its ‘survival’ and replicative machinery. These molecules could also modulate the immune response associated SARS-CoV-2 infection (Chinsembu, 2020). In particular, Mpro inhibitors were extensively studied because of the importance of this enzyme in controlling the major phases of the proteolytic process governing the replication of the virus. This chemotrypsin -like protease cleaves the viral RNA-transcripted protein in eleven different sites (Biembrengut, De Souza, 2020; Kanhed et al., 2021). Targeting this enzyme is sought as a specifically good approach in counteracting this pandemic. Thus, we specifically studied the virtual docking interaction of Artemisinin, one of the mostly represented sesquiterpenes’ molecules in Artemisia genus, with the mean protease enzyme (M^pro) of the SARS-CoV-2. Our in silico probe revealed that Artemisinin potently bound to the M^pro site of action and established two to three conventional hydrogen bonds with affinity ranging from -5.2 to -8.1 kcal×mol^-1. Artemisinin interacts with the Cysteine 145 residue within the pocket region of the enzyme (Figure 2). The pharmacological and pharmacokinetic study of the molecule manifests a good oral absorption and bioavailability score (0.55) without any associated toxicity as assessed by the ADMET properties, which explains its ethno-pharmacological use.

FIGURE 2
The chemical structure of Artemesinin (A), illustration of artemesinin (arrow) docked to the ribbon structure of the targeted protein (M^pro) (B) and the established hydrogen bonds (C). (D) The bi-dimensional diagram of interaction within the ligand-receptor complex.

While specific and concise experimental and clinical trials are still required to verify the importance of these herbal molecules in treating covid-19 patients (Kapepula et al., 2020), the scientific culminating reports concerning this issue corroborate our findings and prompt the idea of possible use of Artemisia plants to fight the covid-19.

APROACH TO USE ARTEMISIA HERBS IN COVID-19 FIGHT

Many reported findings might plead in favor of the Artemisia herbs’ consideration in fighting covid-19. In general, Artemisia species are safely utilized in traditional medicine, except for people suffering from hypersensitivity to their pollen and in cases of excessive intake where patients might develop anaphylaxis and renal disorders, respectively (Nauffal, Gabardi, 2016; Pablos et al., 2019; Tang et al., 2015; Aloui et al., 2010; Steven et al., 1997). To our knowledge, the inhalation route of the plant powder is the first reported one throughout the literature. Such pathway has the propensity to directly target the virus that exists in the whole airway, and to reach epithelia at the viral penetrating interface. In this regard, the molecules are suggested to exert all their potential (neutralizing the virus, inhibiting its penetrance to the host cell and its replication through repressing the virus proteases pathway) to inhibit the virus and the infected lung’s inflammatory process and oxidative stress status; and to ameliorate the blood rheology and coagulability. Accordingly, the exploration of such administration route of the plant extract to counteract the disease might be a promising approach. To better ameliorate the effectiveness of Artemisia molecules, it is suggested to combine both the oral plant’s infusion intake and its powder inhalation in order to neutralize/ inhibit the disseminated viron inside the organism. Herein, the plant aerial parts powder could be replaced by its aqueous maceration that might be pulverized to facilitate its inhalation; particularly in severe cases to prevent additional mechanical damages of infected epithelial cells. In the absence of experimental and clinical evidenced effects of the plant products against covid-19, its ethno-pharmacological application is still limited only to non-severe cases.

CONCLUDING RREMARKS

Artemisia herbs are very rich in biologically active substances. In particular, they show relevant antiviral effects. Within their worldwide large distribution and their non-toxic profile, except for hypersensitive peoples, they are sought as a good candidate to fight the covid-19 syndrome. We hope that deeper clinical investigations of such approach might help saving lives by management of SARS-CoV-2 inducing covid-19.

REFERENCES

Abid Ali Khan MM, Jain DC, Bhakuni RS, Zaim M, Thakur RS. Occurrence of some antiviral sterols in Artemisia annua. Plant Sci. 1991;75(2):161-165.
Akacha A, Badraoui B, Rebai T, Zourgui A. Effect of Opuntia ficus indica extract on methotrexate-induced testicular injury: a biochemical, docking and histological study. J Biomol Struct Dyn. 2020;1-11.
Akrout A, Chemli R, Chreif T, Hammami M. Analysis of the essential oil of Artemisia campestris L. Flavour Fragr J. 2001;16(5):337-339.
Alamgeer Younis, W, Asif H, Sharif A, Riaz H, Bukhari IA, et al. Traditional medicinal plants used for respiratory disorders in Pakistan: a review of the ethno-medicinal and pharmacological evidence. Chin Med. 2018;13:48.
Aloui S, Skhiri H, Ltaief A, Elmay M. An exceptional case of acute renal failure: is there a renal toxicity of Artemisia herba-alba. Renal Failure. 2010;32(8):1009-1011.
Arbab AH, Perez MK, Al-Dosari MS, Al-Rehaily AJ. In vitro evaluation of novel antiviral activities of 60 medicinal plants extracts against hepatitis B virus. Exp Ther Med. 2017;14(1):626-634.
Badraoui R, Adnan M, Bardakci F, Alreshidi MM. Chloroquine and Hydroxychloroquine Interact Differently with ACE2 Domains Reported to Bind with the Coronavirus Spike Protein: Mediation by ACE2 Polymorphism. Molecules. 2021;26(3):673
Badraoui R, Alrashedi MM, El-May MV, Bardakci F. Acute respiratory distress syndrome: a life threatening associated complication of SARS-CoV-2 infection inducing COVID-19. J Biomol Struct Dyn . 2020a;1-11
Badraoui R, Rebai T, Elkahoui S, Alreshidi M, Veettil VN, Noumi E, et al. Allium subhirsutum L. as a potential source of antioxidant and anticancer bioactive molecules: HR-LCMS phytochemical profiling, in vitro and in vivo pharmacological study. Antioxidants. 2020b;9(10):1003.
Biembrengut IV, De Souza TACB. Coagulation modifiers targeting SARS-CoV-2 main protease Mpro for COVID-19 treatment: an in silico approach. Mem Inst Oswaldo, Rio de Janeiro. 2020;115:e200179.
Bora KS, Sharma A. The genus Artemisia: a comprehensive review. Pharmaceutical Biol. 2011;49(1):101-109.
Braithwaite M, Van Vuuren SF, Vijoen AM. Validation of smoke inhalation therapy to treat microbial infections. J Ethnopharmacol. 2008;119(3):501-506.
Brochot A, Guilbot A, Haddioui L, Roques C. Antibacterial, antifungal, and antiviral effects of three essential oil blends. MicrobiologyoOpen. 2017;6(4):e00459.
Calderone V, Nicoletti E, Bandecchi P, Pistello M, Mazzetti P, Martinotti E, et al. In vitro antiviral effects of an aqueous extract of Artemisia verlotorum Lamotte (Asteraceae). Phytother Res. 1998;12(8):595-597.
Cheng F, Chan KH, Jiang Y, Kao RYT, Lu HT, Fan KW, et al. In vitro succeptibility of 10 clinical isolates of SARS coronavirus to selected antiviral products. J Clin Virol. 2004;31(1):69-75.
Chinsembu KC. Coronaviruses and nature’s pharmacy for relief of coronavirus disease 2019. Rev Bras Farmacogn. 2020;1-19.
D’Alessandro S, Scaccabarozzi D, Signorini L, Perego F, Ilboudo DP, Ferante P, et al. The use of antimalarial drug against viral infection. Microorganisms. 2020;8(1):85 8010085.
Dib I, Al Alaoui-Faris FZ. Artemisia campestris L: review on taxonomical aspects, cytogeography, biological activities and bioactive compounds. Biomed Pharmacother. 2019;109:1884-1906.
Efferth T, Romero MR, Wolf DG, Stamminger T, Marin JJG, Marschall M. The antiviral activities of artemisinin and artesunate. Clin Infect Dis. 2008;47(6):804-811.
Efferth T. Beyond malaria: the inhibition of viruses by artemesinin-type compounds. J Biotechnol Adv. 2018;36(6):1730-1737.
Giannis D, Ziogas IA, Gianni P. Coagulation disorder in coronavirus infected patients: Covid-19, SARS-Cov-1, MERS-Cov and lessons from the past. J Clin Virol . 2020;127:104362.
Gonzalez JJE. COVID-19 physiopathology. Med Crit. 2020;34(3):173-175.
Han Y, Ding Y, Xie D, Hu D, Li P, Li X, et al. Design, synthesis, and antiviral activity of novel rutin derivatives containing 1’ 4-pentadien-3-one moeity. Eur J Med Chem. 2015:92:732-737.
Ivanescu B, Miron A, Corciova A. Sesquiterpene lactones from Artemisia genus : biological activities and methods of analysis. J Anal Methods Chem. 2015;2015:247685.
Kanhed AM, Patel DV, Tell DM, Patel NR, Chhabria MT, Yadav MR. Identification of potential Mpro inhibitors for the treatment of COVID-19 by using systematic virtual screening approach. Mol Divers. 2021;25(1):383-401.
Kapepula PM, Kabengele JK, Kingombe M, Van Bambeke F, Tulkens PM, Kishabongo AS, et al. Artemisia spp. Derivatives for COVID-19 treatment: anecdotal use, political hype, treatment potential, challenges, and road map to randomized clinical trials. Am J Trop Med Hyg. 2020;103(3):960-964.
Karamoddini MK, Emami AE, Ghannad MS, Sanin AE, Sahebkar A. Antiviral activities of aerial subsets of Artemisia species against herpes simplex virus type 1 (HSV) in vitro. Asian Biomed. 2011;5(1):63-68.
Kim HK, Jeon WK, Ko S. Flavonone glycosides from citrus junos and their anti-influenza virus activity. Planta Med. 2001;67(6):548-549.
Kim NS, Kim HS, Nam GS, Hwang SW, Hwang SY. The anti-inflammatory and analgesic activities of Artemisia capillaris Thunberg. Kor J Pharmacogn. 2005;36(4):338-343.
Krebs S, Omer TN, Omer B. Wormwood (Artemisia absinthium) supresses tumour necrosis factor alpha and accelerates healing in patients with Crohn’s disease- a controlled clinical trial. Phytomedicine. 2010;17(5):305-309.
Kursat M, Emre I, Yilmaz O, Civelek S, Demir E, Turkoglu I. Phytochemical contents of five Artemisia species. Not Sci Biol. 2015;7(4):495-499.
Lai F, Sinico C, De Logu A, Zaru M, Muller RH, Fadda AM. SLN as topical delivery system for Artemisia arborescens essential oil: in vitro antiviral activity and skin permeation study. Inter J Nanomed. 2007;2(3):419-425
Li SY, Chen C, Zhang HQ, Guo HY, Wang H, Wang L, et al. Identification of natural compounds with antiviral activities against SARS-associated coronovirus. Antiviral Res. 2005;67(1):18-23.
Lis A, Kowal M. Constituents of the essential oils from different organs of Artemesia campestris L. subsp. campestris. J Essent Oil Res. 2015;27(6);1073184.
Lubbe A, Seibert I, Klimkalt T, van der Kooy F. Ethnopharmacology in overdrive: the remarkable anti-HIV activity of Artemisia annua. J Ethnopharmacol . 2012;141(3):854-859.
Lv JL, Li ZZ, Zhang LB. Two new flavonoids from Artemisia argyi with their anticoagulation activities. Nat Prod Res. 2017;32(6):632-639.
Ma C-M, Nakamura N, Hattori M. inhibitory effects on HIV-1 protease of tri-p-coumaroylspermidine from Artemisia caruifolia and related amides. Chem Pharm Bull. 2001;49(7):915-917.
McCutcheon AR, Roberts TE, Gibbons E, Ellis SM, Babiuk LA, Hancock REW, et al. Antiviral screening of Britich Columbian medicinal plants. J Ethnopharmacol . 1995;49(2):101-110.
Messaoudene D, Belguendouz H, Ahmedi ML, Benabdekader T, OTmani F, Terahi M, et al. Ex vivo effects of flavonoids extracted from Artemisia herba alba on cytokines and nitric oxide production in Algerian patients with Adamantiades-Behcet’s disease. J Inflam. 2011;8:35.
Mitrocotsa D, Mitaku S, Axarlis S, Harvala C, Malamas M. Evalauation of the antiviral activity of kaempferol and its glycosides against human cytomegalovirus. Planta Med . 2000;66(4):377-379.
Nauffal M, Gabardi S. Nephrotoxicity of natural products. Blood Purif. 2016;41(1-3):123-129.
Nigam M, Atanassova M, Mishra AP, Pezzani R, Devkota HP, Plygun S, et al. Bioactive compounds and health benefits of Artemisia species. Nat Prod Comm. 2019;17(3):2542-2566.
Pablos I, Egger M, Vejvar E, Reichl V, Briza P, Zennaro D, et al. Similar allergenicity to different Artemisia species is a consequence of highly cross-reactive Artv1-like molecules. Medicina. 2019;55(8):504.
Pereira CG, Barreira l, Bijttebier S, Pieters L, Marques C, Santos TF, et al. Health promoting potential of herbal teas and tinctures from Artemisia campestris ssp. maritime: from traditional remedies to prospective products. Sci Rep. 2018;8(1):4689.
Romero MR, Serrano MA, Vallejo M, Efferth T, Alvarez M, Marin JJG. Antiviral effect of artemisinin from Artemisia annua against a model member of the Flaviviridae family, the bovine viral diarrhoea virus (BVDV). Planta Med . 2006;72(13):1169-1174.
Ryu R, Jung UJ, Kim HJ, Lee W, Bae JS, Park YB, et al. Anticoagulant and antiplatelet activities of Artemisia principles Pampanini and its bioactive components. Prev Nutr Food Sci, 2013;18(3):181-187.
Saddi M, Sanna A, Cottiglia F, Chisu L, Casu L, Bonsignore L, et al. Anti-herpevirus activity of Artemisia arborescens essential oil and inhibition of lateral diffusion in Vero cells. Ann Clin Microbiol Antimicrob. 2007;6:10.
Saoudi M, Badraoui R, Bouhajja H, Ncir M, Rahmouni F, Grati M, et al. Deltamethrin induced oxidative stress in kidney and brain of rats: Protective effect of Artemisia campestris essential oil. Biomed Pharmacother . 2017;94:955-963.
Saoudi M, Badraoui R, Rahmouni F, Jamoussi K, El Feki A. Antioxidant and protective effects of Artemisia campestris essential oil against chlorpyrifos-induced kidney and liver injuries in rats. Front Physiol. 2021;12(194):1-10.
Shahriyary L, Yazdanparast R. Antiplatelet and antithrombotic activities of Artemisia dracunculus L leaves extract. Pharmacology online. 2009;1:217-228.
Shin NR, Park SH, Ko JW, Ryu HW, Jeong SH, Kim JC, et al. Artemisia argyi attenuates airway inflammation in lipopolysaccharide induced acute lung injury model. Lab Anim Res. 2017;33(3):209-215.
Siddiqui AJ, Danciu C, Ashraf SA, Moin A, Singh R, Alreshidi M, et al. Plants-derived biomolecules as potent antiviral phytomedicines: New insights on ethnobotanical evidences against coronaviruses. Plants. 2020;9(9):1244.
Sinico C, De Logu A, Lai F, Velenti D, Manconi M, Loy G, et al. Liposomal incorporation of Artemisia arborescens L essential oil and in vitro antiviral activity. Eur J Pharm Biopharm. 2005;59(1):161-168.
Steven D, Weibord MD, Soule JB, Kimmel PL. Poison on line-acute renal failure caused by oil of wormwood purchased through the internet. N Engl J Med. 1997;337(12):825-827.
Tang R, Sun JL, Yin J, Li Z. Artemisia allergy reaction in China. BioMed Res Int. 2015;179426.
Vetter P, Eckerle I, Kaiser L. Covid-19 : a puzzle with many missing pieces. BMJ. 2020;368:m627.
Wang B, Sui J, Yu Z, Zhu L. Screening the hemostatic active fraction of Artemisia annua L in vitro. Iran J Pharm Res. 2011;10(1):57-62.
Wang L, Si L, Li Y, Wang H, Xu F, Bian H, et al. study on mechanism and active ingredient of Artemisia scoparia axtracts against influenza virus. Lat Am J Pharm. 2017;36(7):1355-1360.
Wu JT, Leung K, Bushman M, Kishoore N, Niehus R, De Salazar PM, et al. Estimating clinical severity of Covid-19 from the transmission dynamics in Wuhan, China. Nature Med. 2020a;26(4):506-510. doi: 10.1038/s41591-020-0822-7
» https://doi.org/10.1038/s41591-020-0822-7
Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, Li SB, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ. 2020b;368:m606.
Yang C, Hu DH, Feng Y. Essential oil of Artemisia vestita exhibits potent in vitro and in vivo antibacterial activity: investigation of the effect of oil on biofilm formation, leakage of potassium ions and survival curve measurement. Mol Med Reports. 2015;12(4):5762-5770.
Yang X, Xiong X, Yang G, Wang J. Effectiveness of stimulation of acupoint KI 1 by Artemisia vulgaris (moxa) for the treatment of essential hypertension: a systemic review of randomized controlled trials. Evidence-Based Compl Altern Med. 2014;2014:187484.
Yoon WJ, Moon JY, Song G, Lee YK, Han MS, Lee JS, et al. Artemisia fukudo essential oil attenuates LPS-induced inflammation by suppressing NF-κB and MAPK activation in raw 264.7 macrophages. Food Chem Toxicol. 2010;48(5):1222-1229.
Yuki K, Fujiogi M, Koutsogiannaski S. Covid-19 pathophysiology: a review. Clin Immunol. 2020;215:108427.

Publication Dates

Publication in this collection
17 Feb 2023
Date of issue
2022

History

Received
25 May 2020
Accepted
22 Apr 2021

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] Abid Ali Khan MM, Jain DC, Bhakuni RS, Zaim M, Thakur RS. Occurrence of some antiviral sterols in Artemisia annua. Plant Sci. 1991;75(2):161-165.

[2] Akacha A, Badraoui B, Rebai T, Zourgui A. Effect of Opuntia ficus indica extract on methotrexate-induced testicular injury: a biochemical, docking and histological study. J Biomol Struct Dyn. 2020;1-11.

[3] Akrout A, Chemli R, Chreif T, Hammami M. Analysis of the essential oil of Artemisia campestris L. Flavour Fragr J. 2001;16(5):337-339.

[4] Alamgeer Younis, W, Asif H, Sharif A, Riaz H, Bukhari IA, et al. Traditional medicinal plants used for respiratory disorders in Pakistan: a review of the ethno-medicinal and pharmacological evidence. Chin Med. 2018;13:48.

[5] Aloui S, Skhiri H, Ltaief A, Elmay M. An exceptional case of acute renal failure: is there a renal toxicity of Artemisia herba-alba. Renal Failure. 2010;32(8):1009-1011.

[6] Arbab AH, Perez MK, Al-Dosari MS, Al-Rehaily AJ. In vitro evaluation of novel antiviral activities of 60 medicinal plants extracts against hepatitis B virus. Exp Ther Med. 2017;14(1):626-634.

[7] Badraoui R, Adnan M, Bardakci F, Alreshidi MM. Chloroquine and Hydroxychloroquine Interact Differently with ACE2 Domains Reported to Bind with the Coronavirus Spike Protein: Mediation by ACE2 Polymorphism. Molecules. 2021;26(3):673

[8] Badraoui R, Alrashedi MM, El-May MV, Bardakci F. Acute respiratory distress syndrome: a life threatening associated complication of SARS-CoV-2 infection inducing COVID-19. J Biomol Struct Dyn . 2020a;1-11

[9] Badraoui R, Rebai T, Elkahoui S, Alreshidi M, Veettil VN, Noumi E, et al. Allium subhirsutum L. as a potential source of antioxidant and anticancer bioactive molecules: HR-LCMS phytochemical profiling, in vitro and in vivo pharmacological study. Antioxidants. 2020b;9(10):1003.

[10] Biembrengut IV, De Souza TACB. Coagulation modifiers targeting SARS-CoV-2 main protease Mpro for COVID-19 treatment: an in silico approach. Mem Inst Oswaldo, Rio de Janeiro. 2020;115:e200179.

[11] Bora KS, Sharma A. The genus Artemisia: a comprehensive review. Pharmaceutical Biol. 2011;49(1):101-109.

[12] Braithwaite M, Van Vuuren SF, Vijoen AM. Validation of smoke inhalation therapy to treat microbial infections. J Ethnopharmacol. 2008;119(3):501-506.

[13] Brochot A, Guilbot A, Haddioui L, Roques C. Antibacterial, antifungal, and antiviral effects of three essential oil blends. MicrobiologyoOpen. 2017;6(4):e00459.

[14] Calderone V, Nicoletti E, Bandecchi P, Pistello M, Mazzetti P, Martinotti E, et al. In vitro antiviral effects of an aqueous extract of Artemisia verlotorum Lamotte (Asteraceae). Phytother Res. 1998;12(8):595-597.

[15] Cheng F, Chan KH, Jiang Y, Kao RYT, Lu HT, Fan KW, et al. In vitro succeptibility of 10 clinical isolates of SARS coronavirus to selected antiviral products. J Clin Virol. 2004;31(1):69-75.

[16] Chinsembu KC. Coronaviruses and nature’s pharmacy for relief of coronavirus disease 2019. Rev Bras Farmacogn. 2020;1-19.

[17] D’Alessandro S, Scaccabarozzi D, Signorini L, Perego F, Ilboudo DP, Ferante P, et al. The use of antimalarial drug against viral infection. Microorganisms. 2020;8(1):85 8010085.

[18] Dib I, Al Alaoui-Faris FZ. Artemisia campestris L: review on taxonomical aspects, cytogeography, biological activities and bioactive compounds. Biomed Pharmacother. 2019;109:1884-1906.

[19] Efferth T, Romero MR, Wolf DG, Stamminger T, Marin JJG, Marschall M. The antiviral activities of artemisinin and artesunate. Clin Infect Dis. 2008;47(6):804-811.

[20] Efferth T. Beyond malaria: the inhibition of viruses by artemesinin-type compounds. J Biotechnol Adv. 2018;36(6):1730-1737.

[21] Giannis D, Ziogas IA, Gianni P. Coagulation disorder in coronavirus infected patients: Covid-19, SARS-Cov-1, MERS-Cov and lessons from the past. J Clin Virol . 2020;127:104362.

[22] Gonzalez JJE. COVID-19 physiopathology. Med Crit. 2020;34(3):173-175.

[23] Han Y, Ding Y, Xie D, Hu D, Li P, Li X, et al. Design, synthesis, and antiviral activity of novel rutin derivatives containing 1’ 4-pentadien-3-one moeity. Eur J Med Chem. 2015:92:732-737.

[24] Ivanescu B, Miron A, Corciova A. Sesquiterpene lactones from Artemisia genus : biological activities and methods of analysis. J Anal Methods Chem. 2015;2015:247685.

[25] Kanhed AM, Patel DV, Tell DM, Patel NR, Chhabria MT, Yadav MR. Identification of potential Mpro inhibitors for the treatment of COVID-19 by using systematic virtual screening approach. Mol Divers. 2021;25(1):383-401.

[26] Kapepula PM, Kabengele JK, Kingombe M, Van Bambeke F, Tulkens PM, Kishabongo AS, et al. Artemisia spp. Derivatives for COVID-19 treatment: anecdotal use, political hype, treatment potential, challenges, and road map to randomized clinical trials. Am J Trop Med Hyg. 2020;103(3):960-964.

[27] Karamoddini MK, Emami AE, Ghannad MS, Sanin AE, Sahebkar A. Antiviral activities of aerial subsets of Artemisia species against herpes simplex virus type 1 (HSV) in vitro. Asian Biomed. 2011;5(1):63-68.

[28] Kim HK, Jeon WK, Ko S. Flavonone glycosides from citrus junos and their anti-influenza virus activity. Planta Med. 2001;67(6):548-549.

[29] Kim NS, Kim HS, Nam GS, Hwang SW, Hwang SY. The anti-inflammatory and analgesic activities of Artemisia capillaris Thunberg. Kor J Pharmacogn. 2005;36(4):338-343.

[30] Krebs S, Omer TN, Omer B. Wormwood (Artemisia absinthium) supresses tumour necrosis factor alpha and accelerates healing in patients with Crohn’s disease- a controlled clinical trial. Phytomedicine. 2010;17(5):305-309.

[31] Kursat M, Emre I, Yilmaz O, Civelek S, Demir E, Turkoglu I. Phytochemical contents of five Artemisia species. Not Sci Biol. 2015;7(4):495-499.

[32] Lai F, Sinico C, De Logu A, Zaru M, Muller RH, Fadda AM. SLN as topical delivery system for Artemisia arborescens essential oil: in vitro antiviral activity and skin permeation study. Inter J Nanomed. 2007;2(3):419-425

[33] Li SY, Chen C, Zhang HQ, Guo HY, Wang H, Wang L, et al. Identification of natural compounds with antiviral activities against SARS-associated coronovirus. Antiviral Res. 2005;67(1):18-23.

[34] Lis A, Kowal M. Constituents of the essential oils from different organs of Artemesia campestris L. subsp. campestris. J Essent Oil Res. 2015;27(6);1073184.

[35] Lubbe A, Seibert I, Klimkalt T, van der Kooy F. Ethnopharmacology in overdrive: the remarkable anti-HIV activity of Artemisia annua. J Ethnopharmacol . 2012;141(3):854-859.

[36] Lv JL, Li ZZ, Zhang LB. Two new flavonoids from Artemisia argyi with their anticoagulation activities. Nat Prod Res. 2017;32(6):632-639.

[37] Ma C-M, Nakamura N, Hattori M. inhibitory effects on HIV-1 protease of tri-p-coumaroylspermidine from Artemisia caruifolia and related amides. Chem Pharm Bull. 2001;49(7):915-917.

[38] McCutcheon AR, Roberts TE, Gibbons E, Ellis SM, Babiuk LA, Hancock REW, et al. Antiviral screening of Britich Columbian medicinal plants. J Ethnopharmacol . 1995;49(2):101-110.

[39] Messaoudene D, Belguendouz H, Ahmedi ML, Benabdekader T, OTmani F, Terahi M, et al. Ex vivo effects of flavonoids extracted from Artemisia herba alba on cytokines and nitric oxide production in Algerian patients with Adamantiades-Behcet’s disease. J Inflam. 2011;8:35.

[40] Mitrocotsa D, Mitaku S, Axarlis S, Harvala C, Malamas M. Evalauation of the antiviral activity of kaempferol and its glycosides against human cytomegalovirus. Planta Med . 2000;66(4):377-379.

[41] Nauffal M, Gabardi S. Nephrotoxicity of natural products. Blood Purif. 2016;41(1-3):123-129.

[42] Nigam M, Atanassova M, Mishra AP, Pezzani R, Devkota HP, Plygun S, et al. Bioactive compounds and health benefits of Artemisia species. Nat Prod Comm. 2019;17(3):2542-2566.

[43] Pablos I, Egger M, Vejvar E, Reichl V, Briza P, Zennaro D, et al. Similar allergenicity to different Artemisia species is a consequence of highly cross-reactive Artv1-like molecules. Medicina. 2019;55(8):504.

[44] Pereira CG, Barreira l, Bijttebier S, Pieters L, Marques C, Santos TF, et al. Health promoting potential of herbal teas and tinctures from Artemisia campestris ssp. maritime: from traditional remedies to prospective products. Sci Rep. 2018;8(1):4689.

[45] Romero MR, Serrano MA, Vallejo M, Efferth T, Alvarez M, Marin JJG. Antiviral effect of artemisinin from Artemisia annua against a model member of the Flaviviridae family, the bovine viral diarrhoea virus (BVDV). Planta Med . 2006;72(13):1169-1174.

[46] Ryu R, Jung UJ, Kim HJ, Lee W, Bae JS, Park YB, et al. Anticoagulant and antiplatelet activities of Artemisia principles Pampanini and its bioactive components. Prev Nutr Food Sci, 2013;18(3):181-187.

[47] Saddi M, Sanna A, Cottiglia F, Chisu L, Casu L, Bonsignore L, et al. Anti-herpevirus activity of Artemisia arborescens essential oil and inhibition of lateral diffusion in Vero cells. Ann Clin Microbiol Antimicrob. 2007;6:10.

[48] Saoudi M, Badraoui R, Bouhajja H, Ncir M, Rahmouni F, Grati M, et al. Deltamethrin induced oxidative stress in kidney and brain of rats: Protective effect of Artemisia campestris essential oil. Biomed Pharmacother . 2017;94:955-963.

[49] Saoudi M, Badraoui R, Rahmouni F, Jamoussi K, El Feki A. Antioxidant and protective effects of Artemisia campestris essential oil against chlorpyrifos-induced kidney and liver injuries in rats. Front Physiol. 2021;12(194):1-10.

[50] Shahriyary L, Yazdanparast R. Antiplatelet and antithrombotic activities of Artemisia dracunculus L leaves extract. Pharmacology online. 2009;1:217-228.

[51] Shin NR, Park SH, Ko JW, Ryu HW, Jeong SH, Kim JC, et al. Artemisia argyi attenuates airway inflammation in lipopolysaccharide induced acute lung injury model. Lab Anim Res. 2017;33(3):209-215.

[52] Siddiqui AJ, Danciu C, Ashraf SA, Moin A, Singh R, Alreshidi M, et al. Plants-derived biomolecules as potent antiviral phytomedicines: New insights on ethnobotanical evidences against coronaviruses. Plants. 2020;9(9):1244.

[53] Sinico C, De Logu A, Lai F, Velenti D, Manconi M, Loy G, et al. Liposomal incorporation of Artemisia arborescens L essential oil and in vitro antiviral activity. Eur J Pharm Biopharm. 2005;59(1):161-168.

[54] Steven D, Weibord MD, Soule JB, Kimmel PL. Poison on line-acute renal failure caused by oil of wormwood purchased through the internet. N Engl J Med. 1997;337(12):825-827.

[55] Tang R, Sun JL, Yin J, Li Z. Artemisia allergy reaction in China. BioMed Res Int. 2015;179426.

[56] Vetter P, Eckerle I, Kaiser L. Covid-19 : a puzzle with many missing pieces. BMJ. 2020;368:m627.

[57] Wang B, Sui J, Yu Z, Zhu L. Screening the hemostatic active fraction of Artemisia annua L in vitro. Iran J Pharm Res. 2011;10(1):57-62.

[58] Wang L, Si L, Li Y, Wang H, Xu F, Bian H, et al. study on mechanism and active ingredient of Artemisia scoparia axtracts against influenza virus. Lat Am J Pharm. 2017;36(7):1355-1360.

[59] Wu JT, Leung K, Bushman M, Kishoore N, Niehus R, De Salazar PM, et al. Estimating clinical severity of Covid-19 from the transmission dynamics in Wuhan, China. Nature Med. 2020a;26(4):506-510. doi: 10.1038/s41591-020-0822-7
» https://doi.org/10.1038/s41591-020-0822-7

[60] Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, Li SB, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ. 2020b;368:m606.

[61] Yang C, Hu DH, Feng Y. Essential oil of Artemisia vestita exhibits potent in vitro and in vivo antibacterial activity: investigation of the effect of oil on biofilm formation, leakage of potassium ions and survival curve measurement. Mol Med Reports. 2015;12(4):5762-5770.

[62] Yang X, Xiong X, Yang G, Wang J. Effectiveness of stimulation of acupoint KI 1 by Artemisia vulgaris (moxa) for the treatment of essential hypertension: a systemic review of randomized controlled trials. Evidence-Based Compl Altern Med. 2014;2014:187484.

[63] Yoon WJ, Moon JY, Song G, Lee YK, Han MS, Lee JS, et al. Artemisia fukudo essential oil attenuates LPS-induced inflammation by suppressing NF-κB and MAPK activation in raw 264.7 macrophages. Food Chem Toxicol. 2010;48(5):1222-1229.

[64] Yuki K, Fujiogi M, Koutsogiannaski S. Covid-19 pathophysiology: a review. Clin Immunol. 2020;215:108427.