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. 2020 Aug 20:10.1002/ptr.6786. Online ahead of print. doi: 10.1002/ptr.6786

Phytotherapeutic options for the treatment of COVID‐19: A concise viewpoint

Misbahud Din 1, Fawad Ali 2, Abdul Waris 1, Fatima Zia 1, Muhammad Ali 1,✉
PMCID: PMC7461328  PMID: 32815574

Abbreviations

ADV

Aleutian disease virus

CMV

Cytomegalovirus

CVB

Coxsackie B virus

CXV

Cactus X virus

ESV

Espirito Santo virus

HBV

Hepatitis B virus

HIV

human immunodeficiency virus

HSV

Herpes simplex virus

JEV

Japanese encephalitis virus

KSHV

Kaposi sarcoma herpes virus

PV

polio virus

RSV

respiratory syncytial virus

SARS‐CoV

severe acute respiratory syndrome coronavirus

VHSH

viral hemorrhagic septicemia virus

VSV

vesicular stomatitis virus

VV

vaccinia virus

VZV

varicella zoster virus

In December 2019 in Wuhan city of China, a novel coronavirus emerged which was provisionally named as 2019‐nCoV responsible for causing the Coronavirus Disease‐2019 (COVID‐19). As of May 2020, the WHO reported more than 4 million positive cases of COVID‐19 all over the world.

Currently, no vaccine exists for the treatment of COVID‐19 and limited therapeutic options are available (Li & De Clercq, 2020). For centuries, traditional medicines have been used to cure several diseases including viral infections (Ahmad et al., 2020). The phytotherapy‐based approach to find new drugs have contributed as several plant species are a great source of modern medicines (Yaseen et al., 2019). Similarly, plant‐derived active compounds have been studied as viral inhibitors for many years (Serkedjieva, Manolova, Zgórniak‐Nowosielska, Zawilińska, & Grzybek, 1990). This study was aimed to briefly describe the potential use of ethno‐medicinal research in searching new therapeutic options against COVID‐19 and other coronaviruses and to provide some important directions to researcher for planning future studies. We have summarized various medicinal plants and their reported antiviral activities in Table 1. There is the possibility that studies on plant‐derived compounds listed in Table 1 have been not carried according to more recent scientific qualitative standards for plant‐derived products (Heinrich et al., 2020). For example, there is the possibility that high concentrations or doses have been used. The antiviral activities of medicinal plants have been mostly derived from laboratory studies (as clinical data are limited) and referred to multicomponent preparation of traditional medicines (Liu, Zhang, He, & Li, 2012). Similarly, the qualitative standards for reporting clinical trials in herbal medicine are not as rigorous as in the conventional pharmaceutical field (Williamson, Liu, & Izzo, 2020). In a study in 2012, it was reported that traditional herbal remedies along with Western medicines could help to improve symptoms, absorptions of pulmonary infiltrations, life‐quality, and decrease corticosteroids uses in SARS patients (Liu et al., 2012).

TABLE 1.

Medicinal plants and reported antiviral compounds

S. No. Plant name Family Active compounds Effective against virus References
1 Plantago major L. Plantaginaceae Caffeic acid, chlorogenic acid HSV‐I, HSV‐II, ADV‐III, and ADV‐II Nazarizadeh, Mikaili, Moloudizargari, Aghajanshakeri, & Javaherypour, 2013; Samuelsen, 2000
2 Solanum torvum Solanaceae Torvanol‐A, Torvanol‐H HSV‐I Ikeda et al., 2000
3 Euphorbia jokini Euphorbiaceae Diterpenes, putranjivain A HSV‐II Cheng et al., 2004
4 Cassia javanica Caesalpiniaceae Ent‐epiafzel‐echin(4a‐8)epiafzelechin(EEE,S) HSV‐II Kashiwada et al., 1990
5 Melaleuca alternifolia Myrtaceae Isoborneal HSV‐I Hammer, Carson, & Riley, 2002
6 Phylanthus amarus Phyllanthaceae Elgic acid HBV Blumberg, Millman, Venkates, & Thyagarajan, 1990
7 Bohmeria nivea Urticaceae HBV Chang, Huang, Yuan, Lai, & Hung, 2010
8 Camellia sinensis Theaceae Tannic acid, theaflavin 3 gallate, theaflavin‐33‐gallate HIV, HCV, influenza Oh et al., 2013
9 Dryopteris crassirhizoma Dryopteridaceae Kampferol HIV Min, Tomiyama, Nakamura, & Hattori, 2001
10 Paeonia lactiflora Paeoniaceae Penta‐o‐gallyl‐βD‐glucose HBV Lee, Lee, Jung, & Mar, 2006
11 Verbescum thapsiforme Scrophulariaceae Iridoid, phenyl thanoid HSV‐I, influenza A and B, H7N Zgorniak‐Nowosielska, Grzybek, Manolova, Serkedjieva, & Zawilińska, 1991
12 Radix glycyrrhiza Fabaceae Glycyrrhizin Influenza, SARS‐CoV Fang et al., 2007; Yang, Islam, Wang, Li, & Chen, 2020
13 Aesculus chinensis Sapindaceae Flavonoids RSV, influenza, rubella Liu, Wang, Lee, Wang, & Du, 2008; Wei et al., 2004
14 Melia azedarach Meliaceae Meliacine, cinnamoyl dihydroxymeliacarpin HSV‐I and HSV‐II, Junin virus, Sindbis virus, VSV, poliovirus, pseudorabies virus, tacaribe virus Andrei, Coto, & de Torres, 1985; Andrei, Damonte, de Torres, & Coto, 1988; Andrei, Lampuri, Coto, & De Torres, 1986; Castilla, Barquero, Mersich, & Coto, 1998
15 Humulus lupulus Cannabaceae Xanthohumol HSV and HIV Wang, Ding, Liu, & Zheng, 2004
16 Melissa officinalis Lamiaceae Citral a, citral b, citronellal, monoterpenes, aldehydes, lemon balm oil HSV Cohen, Kucera, & Herrmann, 1964
17 Prunella vulgari Lamiaceae Rosmarinic acid, phenol like apigenin, luteolin derivatives HIV Yao, Wainberg, & Parniak, 1992
18 Geum japonicum Rosaceae Ursolic acid, maslinic acid CMV Yukawa et al., 1996
19 Ocimum basilicum Lamiaceae Ursolic acid (HSV‐I), apigenin (HSV‐II) HSV‐I and HSV‐II Yucharoen, Anuchapreeda, & Tragoolpua, 2011
20 Glycyrrhiza glabra Fabaceae Glycyrrhizic acid VV, HSV, VSV, VZV, SARS‐COV, KSHV, HIV‐I HIV‐II, and influenza virus Fiore et al., 2008
21 Stephania cepharantha Menispermaceae Cepharathine HSV‐I, CVB‐3, HIV, SARS‐CoV Ma et al., 2002
22 Stylogne cauliflora Oligophenols are involved in antiviral activity HCV M Patil, Masand, & Prakash Gupta, 2016
23 Pithecellobium clypearia Leguminosae 7‐ogalloyltricetifavan 7,4‐di‐ogalloylricetifavan HSV‐I, HSV‐II, Junin virus, HBV, tacaribe virus Leung et al., 2006; Li, Leung, Yao, Ooi, & Ooi, 2006
24 Humulus lupulus Cannabaceae Xanthohumol HIV Wang et al., 2004
25 Melissa officinalis Labiatae Citral a, citral b,citronellal, monoterpenes, aldehydes, lemon balm oil HSV Allahverdiyev, Duran, Ozguven, & Koltas, 2004
26 Prunella vulgaris Ericaceae Rosmarinic acid, phenol like apigenin, luteolin derivatives HSV‐I Xu, Lee, Lee, White, & Blay, 1999
27 Geum japonicum Rosaceae Triterpenes HIV Xu, Zeng, Wan, & Sim, 1996
28 Ocimum basilicum Lamiaceae Ursolic acid (HSV‐I), apigenin (HSV‐II) HSV‐I and HSV‐II Yucharoen et al., 2011
29 Olea europea Oleaceae Oleuropein, leaf extract VHSH Antunes et al., 2017
30 Glycine max Leguminosae ADV‐I, CXV‐B1 Müller et al., 2007
31 Lycoris radiata Amaryllidaceae Lycorine and alkaloids; 2αmethoxy‐6‐oethyloduline, 2αmethoxy‐6‐omethyloduline, trispherine SARS‐CoV, influenza He et al., 2013
32 Blumea laciniate Asteraceae Polyphenols RSV Li, Ooi, Wang, But, & Ooi, 2004
33 Geranium sanguineum Geraniaceae Polyphenols RSV, influenza Chattopadhyay et al., 2009
34 Phyllanthus nanus Euphorbiaceae HBV Lam et al., 2006
35 Ardisia chinensis Primulaceae Phenolics HBV Leung et al., 2006
36 Alisma orientalis Alismataceae 25‐anhydroanisol, 13b,17b‐epoxyalisol, alisol b‐23‐acetate, alisol F24 acetate, alisol F HBV Jiang et al., 2006
37 Acacia nilotica Fabaceae Silybin, oxymatrine HCV Rehman, Ashfaq, Riaz, Javed, & Riazuddin, 2011
38 Nerium indicum Apocynaceae Caffeoylquinic acid, quercetin, luteolin‐5o‐rutinisid Influenza, HIV,HSV Farahani, 2014; Kitazato, Wang, & Kobayashi, 2007
39 Elephantopus scabe Asteraceae Polyphenols RSV Li, 2005
40 Eleutherococcs senticosus Araliaceae Ethanolic extract of roots HRV, RSV, influenza virus A Glatthaar‐Saalmüller, Sacher, & Esperester, 2001
41 Syzygium aromaticum Myrtaceae Eugeniin HSV‐I, EBV Carvalho, Andrade, de Sousa, & de Sousa, 2015; Kurokawa et al., 1998
42 Azadiracta indica Meliaceae Aqueous extract of leaves, azadiractin Dengue virus Parida, Upadhyay, Pandya, & Jana, 2002
43 Momordia charantia Cucurbitaceae Lectin MA30 Influenza Ahmad, Javed, Rao, & Husnain, 2016
44 Euphorbia segetalis Euphorbiaceae Lupenone HSV‐I and HSV‐II Álvarez, Habtemariam, & Parra, 2015
45 Guazuma ulmifolia Malvaceae Ethyl acetate extract PV Felipe et al., 2006
46 Argimonia pilosa Rosaceae Polyphenols Influenza virus A and B Shin, Lee, Park, & Seong, 2010
47 Punica granatum Lythraceae Polyphenols HSV‐I, norovirus Živković et al., 2018
48 Myrica rubra Myricaceae Rodelphinidin‐di‐ogallate HSV‐I Cheng et al., 2003
49 Podophyllum peltatum Berberidaceae Podohyllotoxin Measles, HSV Bedows & Hatfield, 1982
50 Psiadia dentate Asteraceae 3‐methylkaemfero PV Robin, Boustie, Amoros, & Girre, 1998
51 Loranthus yadoriki Loranthaceae Camp B,C Coxsackie virus Wang, Yang, Huang, Wen, & Liu, 2000
52 Scutellaia baicalensis Lamiaceae Isoscutellarein‐8methyl ether (5,7,4trihydroxy‐8methoxyflavone) Influenza A Nagai, Moriguchi, Suzuki, Tomimori, & Yamada, 1995
53 Poncirus trifoliate Rutaceae Flavonoids, coumarins, and triterpenoid Influenza Heo et al., 2018
54 Dianella longifolia Asphodelaceae Chrysophanic acid PV Semple, Pyke, Reynolds, & Flower, 2001
55 Callophylum lanigerum Calophyllaceae Calinode A‐1, calonide B‐4 HIV‐I Kashman et al., 1992
56 Curcuma longa Zingiberaceae Curcumin, curcuminoids HIV‐I, HBV, influenza Zorofchian Moghadamtousi et al., 2014
57 Dropteris crassirhizoma Dryopteridaceae Dryocrassin ABBA, Extract, kaemferol acethylrhamnoside Dengue virus Maryam et al., 2020
58 Scutellaria baicalensis Lamiaceae Baicalin, isosceutellarei n‐8‐methylether, wagonin, oroxylin A Influenza A and B, RSV, hepatitis B Hour et al., 2013; Ma et al., 2002
59 Urtica dioica Urticaceae n‐acethylglucosamine HIV‐I, HIV‐II, influenza A De Clercq, 2000; Rajbhandari et al., 2009
60 Brazilian propolis Asteraceae Moronic acid, kaemferol HIV, influenza virus Ito et al., 2001; Kai et al., 2014
61 Artemisia annua L. Asteraceae friedelan3‐β‐ol, artemetin, and quercetagetin 6,7,3′,4′‐tetramethyl ether SARS‐CoV Wang et al., 2007
62 Lycoris radiate Amaryllidaceae Lycorine, glycyrrhizin SARS‐CoV Shahrajabian, Sun, Shen, & Cheng, 2020
63 Glycyrrhiza uralensis Fabaceae HIV, RSV, SARS‐CoV Hoever et al., 2005; Ma et al., 2002
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Abbreviations: ADV, Aleutian disease virus; CMV, Cytomegalovirus; CVB, Coxsackie B virus; CXV, Cactus X virus; HBV, Hepatitis B virus; HIV, human immunodeficiency virus; HSV, Herpes simplex virus; KSHV, Kaposi sarcoma herpes virus; SARS‐CoV, severe acute respiratory syndrome coronavirus; PV, polio virus; RSV, respiratory syncytial virus; VHSH, viral hemorrhagic septicemia virus; VSV, vesicular stomatitis virus; VV, vaccinia virus.

The Traditional Chinese Medicines (TCM) were highly considered by Government of China in their campaign against COVID‐19. To evaluate the safety and efficacy of treatments for COVID‐19 patients, China launched more than 300 clinical trials on March 1, 2020. Among the total treatments, 16.5% (50 trials) were linked to the use TCM where 4.6% (14 cases) were linked to examine the combine use of Western medicine and TCM. Among the trials of TCM, 22 (7.3%) were launched to evaluate the efficacy of self‐made herbal preparations including QingYi‐4, Xin Guan‐1 Formula and Xin Guan‐2 Formula. The commercially available TCM products like Lian Hua Qing Wen capsules and Tan Re Qing injections were also studied in 14 (4.6%) trials (Yang et al., 2020). The therapeutic effects of TCM herbal remedies for the treatment of SARS coronavirus have also been published (Luo et al., 2020; Yang et al., 2020). Regardless the complex formulation of TCM, herbs such as Scutellaria baicalensis and Glycyrrhiza glabra were available in tested TCM preparations. The extracted baicalin and glycyrrhizin compounds from the mentioned herbs have in vitro evidences of anticoronaviral activity (Chen et al., 2004). The anticoronavirus TCM remedies included plants such as Lonicerae japonicae, Saposhnikovia divaricate, Forsythia Vahl, and Atractylodis macrocephalae (Luo et al., 2020). This could identify new directions for future research.

For the treatment of coronavirus infections, two different research streams could be possibly followed to search useful phytotherapeutic compounds. One option is the herbal remedies that have potential preventive effects especially boosting the immune responses, that is, Echinacea purpurea and Astragalus membranaceus (Block & Mead, 2003). Astragals has been used in TCM herbal formulation against SARS (Liu et al., 2012). Immunomodulatory properties of polysaccharides and Uncaria tomentosa (from medicinal mushrooms) could also be used. The second option is the herbal remedies with therapeutic effects that have different antiviral mechanism of action. Regardless the etiology, clinical studies have proposed extract from plants, such as Pelargonium sidoides and Sambucus nigra to treat the infection of respiratory system (Agbabiaka, Guo, & Ernst, 2008; Hawkins, Baker, Cherry, & Dunne, 2019; Kalus et al., 2009). The anticoronaviral activities of polyphenols and pelargonium has also been studied (Michaelis, Doerr, & Cinatl Jr, 2011; Weng et al., 2019). A set of compounds such as quercetin, kaempferol, and cryptotanshinone have been identified with anti‐SARS‐CoV action (Zhang, Wu, Zhang, Deng, & Peng, 2020). Active compounds derived from medicinal plants has different antiviral mechanisms, such as viral pentation inhibition, replication inhibition or inhibiting the SARS‐3CLpro activity (Yang et al., 2020). Such studies can expand the area of plant‐based products to be investigated in future experiments. Similarly, the phytotherapy can be useful in the management or prevention the adverse effects of conventional drugs (Yang et al., 2020).

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

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