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

Aleutian disease virus

Cytomegalovirus

Coxsackie B virus

Cactus X virus

Espirito Santo virus

Hepatitis B virus

human immunodeficiency virus

Herpes simplex virus

Japanese encephalitis virus

Kaposi sarcoma herpes virus

polio virus

respiratory syncytial virus

severe acute respiratory syndrome coronavirus

viral hemorrhagic septicemia virus

vesicular stomatitis virus

vaccinia virus

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

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.