Review Article

Medicinal Plants with Potential Inhibitory Bioactive Compounds against Coronaviruses

Introduction

Drugs are chemically and/or biologically synthesized. Semi-synthesized drugs (e.g. homatropine) are obtained from natural sources while fully synthesized drugs are chemically amalgamated in the laboratory (e.g. paracetamol, aspirin). Hence, plants contain beneficial bioactive compounds that may be valuable for therapeutic purposes or used as precursors for drugs biosynthesis. ¹ The whole plant, part of the plant (e.g. leaves), exudates or extract of plants represent potential sources of bioactive compounds. ² Hence, medicinal plants have been applied since time immemorial and it is important to mention that their use is growing dramatically. ³ Indeed, medicinal plants remain a major source of drug discovery and play an important role in the management of diseases such as infections. ^4-6 It is also worth noting that over 85% of the population in Africa, Asia and in the Middle East use herbal medicine as first line of treatment. ⁷ Interestingly, the Chinese population widely utilizes herbs to control severe acute respiratory syndrome (SARS) caused by coronaviruses (CoVs). CoVs are enveloped single-stranded RNA (ss-RNA) viruses that infect both humans and animals. They are named for the crown-like spikes on their surface, and are classified as alpha, beta, gamma, and delta. ⁸ They affect the respiratory, gastrointestinal and central nervous systems. ⁹ Mechanistically, the CoVs-mediated infection is initiated by the entry of the virus into host cells through binding of the viral spike protein (S-protein) to angiotensin-converting enzyme 2 (ACE2) present in the host (mainly epithelial cells such as pneumocytes and enterocytes). Their replication is controlled by the viral 3-chymotrypsin-like cysteine protease (3CLpro), papain-like proteinase (PLpro) and RNA-dependent RNA protease (RdRp) enzyme. ^10,11 Onset of CoVs symptoms occurs within 14 days of infection and decreases thereafter. ^12,13 Transmission appears to spread mainly through respiratory droplets and contact routes. ¹² The two types of human coronaviruses of public health concerns two decades ago were SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) until now the recent outbreak of another CoV known as SARS-CoV-2. These three viruses belong to the genera, beta coronavirus. ¹⁴

Human coronaviruses were isolated nearly 50 years ago but they were only thought to cause mild, self-limiting respiratory disease. ^15-17 The outbreak of SARS-CoV changed this thought and gave scientist a new concept and approach to the CoVs. Since then, CoVs have been established to be endemic in the human populations, causing 15–30% of respiratory disease each year. ¹⁸ They cause more severe disease in children below age 5, the elderly, and individuals with underlying chronic illnesses (e.g. cardio-vascular diseases, diabetes etc).

SARS-CoV-2 was discovered in Wuhan, Hubei, China in December 2019. This virus, of unclear origin, is highly virulent, infectious, contagious and lethal. In less than a month, SARS-CoV-2 known as coronavirus disease 2019 (COVID-19) has spread from people to people to other provinces in China and reach many other countries within three months. ¹⁹ As estimated on April, 18^th 2020, there were 2 160 207 confirmed cases and 146 088 deaths globally from the pandemic. ²⁰

At present, the management of symptomatic patients with COVID-19 mainly involves the use of antiviral, supportive treatment (e.g. corticosteroid and mechanical ventilation) while boosting the patient’s immunity. To date, no chemical therapy is officially considered as successful in terms of efficiency and safety.

This review is carried out at this time as the inhibition of SARS-CoV-2 has defied specific therapeutic intervention. It reviews recent advances in the use of medicinal plants for the supportive treatment and cure of COVID-19. Some medicinal plants that possess bioactive compounds with CoV inhibitory activities that could be applied to prevent, treat, or used as adjuvant therapies in the management of COVID-19 are presented.

Andrographis paniculata

Andrographis paniculata (Burm.f.) Nees (A. paniculata) is a medicinal plant which belongs to the family, Acanthaceae. It is commonly known as the “King of Bitters”.It is widely distributed and used traditionally in China and tropical Asian region in the treatment of infectious diseases, common cold and upper respiratory tract infection, inflammation, fevers, cancer etc. ^21,22 The main bioactive compound of A. paniculata is andrographolide a diterpenoid which has a wide spectrum of antiviral activity among other antimicrobial activities. ²³ There are other bioactive antiviral compounds, such as andrographiside and andrograpanin isolated from this plant. ²⁴ Some studies indicate that A. paniculata possesses inhibitory bioactive compounds against CoVs. ^24,25 Wu et al. deduced that andrographolide and its derivative could serve as new lead compound in drug discovery for the treatment of SARS-CoV-2 infections by inhibiting viral 3CLpro and PLpro enzyme. ²⁴ Also, andrographolide sulphonate is the main active ingredient of “Xiyanping”, a traditional Chinese antiviral and anti-inflammatorymedicine, used as an injection. ^25,26 Itwas used in the treatment of SARS-CoV infection in 2002 as adjuvant therapy with a significant outcome. ²⁷

Rheum species

Rhubarb is the common name of a perennial plant belonging to the genus ‘Rheum’ in the familyPolygonaceae. There are several species of this plant e.g. Rheum emodi Wall., Rheum palmatum L., Rheum officinaleBaill., Rheum tanguticum Maxim. ex Balf. They are known to exert some antiviral activities against CoVs. ^28,29 The most important phytoconstituent of the root extract that possesses this antiviral activity is emodin, an anthraquinone derivative. Ho et al. and Schwarz et al. reported that emodin acts by blocking the binding of SARS-CoV S-protein to the host receptor ACE 2, and suggested that emodin could be considered as a potential lead therapeutic agent for SARS. ^28,30

Polygonum multiflorum

Polygonum multiflorum Thunb. is a perennial plant belonging to the genus polygonumin the family Polygonaceae. It is commonly known as tuber fleece flower, and represents a popular traditional Chinese medicine (TCM) listed in the Chinese Pharmacopoeia (CP). ³¹ Laboratory investigations of various parts of this plant demonstrated that Polygonum multiflorum displays various bioactive components with antibacterial, anti-inflammatory, anti-oxidant and antiviral properties. ^32-34 Like in rhubarb, the most important bioactive compound of this plant is emodin, which was found to exerts inhibitory activity against SARS-CoV. ²⁸

Glycyrrhiza glabra

The root of Glycyrrhiza glabra L. is popularly called liquorice. The plant is an herbaceous perennial legume belonging to the family Leguminosae and widely distributed in Europe and Asia. The most active bioactive compound is glycyrrhizin which acts by inhibiting the interaction between S-protein and ACE2 thereby preventing viral invasion. ^35,36 Pilcher and Cinatl et al suggested that glycyrrhizin should be assessed for the treatment of SARS as an alternative option. ^37,38 Further investigation was done by Hoever et al and Fiore et al who confirmed the activity of glycyrrhizin against SARS coronavirus. ^39,40

Scutellariabaicalensis

Scutellariabaicalensis Georgi, or Chinese skullcap, is a flowering plant belonging to the family Lamiaceae. ⁴¹ It is found abundantly in several East Asian countries and Russia. This plant has been widely used as a medicinal plant in China for thousands of years and has been officially listed in the CP as a medicine to treat various conditions like hepatitis, inflammation, diarrhea, dysentery, hypertension, and respiratory infections. ⁴² The biologically active phytoconstituent of the root extract is baicalin, a flavone glycoside known to have anti-inflammatory, anti-allergic, free radical scavenging and apoptotic activities. ⁴³ This flavonoid can be found in other species from the genus Scutellaria such as Scutellariaamoena and Scutellaria likiangensis. ⁴⁴ Interestingly, baicalin is the most active flavonoid from Scutellaria spp. against virus. ⁴⁵ Wong and Yuen reported baicalin as an antiviral compound with an unknown mechanism that can be used for the management of CoVs with particular reference to SARS. ⁴⁶ More recently, Yang et al ³⁶ reported that baicalin acts by inhibition of ACE 2, making it a valuable antiviral compound in the treatment of patients with SARS-CoV-2.

Quercetin yielding medicinal plants

Quercetin is a bioactive flavonoid present in many plants and some fruits such as green tea (Camellia sinensis), onions (Allium cepa), and apples (Malus domestica). ^47,48 It was used in folk medicine as an antioxidant. Most recently, Smith and Smith reported that quercetin ⁴⁹ is a FDA-approved compound that prevents CoVs from binding to host cell’s ACE2 receptor. However, Nguyen et al. previously reported that quercetin and some other flavonoids in this class act on CoVs by 3CLpro inhibition, ⁵⁰ and this report was substantiated by a most recent study made by Jo et al. ⁵¹ Other flavonoids, such as herbacetin, hesperetin, rhoifolin, pectolinarin, have been proved to possess antiviral activities against CoVs. ^52,53 Some medicinal plants containing these flavonoids include Toona sinensis (Juss.) M.Roem. (family - Meliaceae), ^54,55 Litchi chinensis Sonn (family - Sapindaceae), ⁵⁶ Pichia pastoris (family - Saccharomycetaceae), ⁵⁰ Houttuynia cordataThunb. (family - Saururaceae), ⁵⁷ Sambucus nigraL. (family - Adoxaceae). ⁵⁸

Galla Chinensis

The galls on the leaves of Rhus chinensis Mill. is known as Galla Chinensis. Rhus chinensisis a deciduous flowering shrub belonging to the family Anacardiaceae and widely distributed in Asia and commonly known as sumac. Galla Chinensis has been used in TCM for several years in the treatment of diarrhea and prolonged coughing. ³¹ Djakpo and Yao reported that Galla Chinensis contains strong antiviral properties. ⁵⁹ The bioactive compound of Galla Chinensis that possesses antiviral activity is the polyphenol Tetra-O-galloyl-β-d-glucose (TGG), a tannin. Indeed, Ling et al. discovered that TGG is effective against SARS-CoV with a mechanism that would interfere with the virus entry into host cells. ⁶⁰

Phyllanthus emblica

Phyllanthus emblica L.is an Indian gooseberry originated from a deciduous flowering tree belonging to the family Phyllanthaceae and used in traditional medicines in India to treat cough, constipation, fever and asthma. ⁶¹ This plant possesses various bioactive compounds such as emblicanin, phyllaemblicin, punigluconoin and glochicoccin. ^62-64 Among them, the polyphenol, phyllaemblicin B, an ellagitannin, represents the bioactive compound that has been extensively studied for antiviral activity. ^62,65 Actually, a recent review highlighted phyllaemblicin B as a potential bioactive compound for the treatment of SARS-CoV-2 by inhibiting RdRp. ²⁴ Like in Galla Chinensis, TGG was also found eliciting a good antiviral property in Phyllanthus emblica. ⁶⁶

Isatisindigotica

Isatisindigotica L. is a small flowering plant with a decumbent stem belonging to the family Brassicaceae. It is native to east and central Asia. The dried root of Isatisindigotica is commonly called Ban Lan Gen, Woad root, Indigo wood, or Isatidis Radix. Woad root has been used in the treatment of cold, headache, sore throat, bacterial and viral diseases for several years in China. ^67,68 During the SARS-CoV and MERS pandemic which occurred in 2003 and 2012, respectively, Isatisindigotica was used in the management of people with the said disease. ⁶⁹ The antiviral activity of Isatisindigotica extractwas confirmed by Hsuan et al, Yang et al, and Ping et al. ^70-72 Interestingly, Yang et al and Su et al concluded that the antiviral activity of Isatisindigotica extract is mediated by inhibition of virus attachment. ^71,73 The important bioactive compounds of this plant with antiviral activity are clemastanin B, epigoitrin, sinigrin, indigo, indirubin, beta-sitosterol. ^69,72-74 To date, beta-sitosterol, sinigrin and indigo were shown to be active against CoVs by inhibiting 3CLpro. ^36,69,75

Erigeron breviscapus

Erigeron breviscapus (Vaniot) Handel-Mazzetti is a perennial Chinese flowering herb in the family Compositae and its common name is fleabane. It has been used for many years in TCM. Scutellarin is the most active bioactive compound of this plant having anti-inflammatory, anti-oxidative, anti-platelet, and anti-coagulation properties. ^76,77 It is clinically used to treat diabetes and stroke. ⁷⁸ Yu et al. observed that scutellarin potently inhibited the activity of SARS-CoV protease enzyme in vitro and concluded that it could be a potential SARS-CoV inhibitor. ⁷⁹

Torreya nucifera

Torreya nucifera (L.) Siebold & Zucc.is a large evergreen shrub belonging to the family Taxaceae. It is commonly known as Japanese nutmeg and it is native to Japan and South Korea. The seed of this plant is used as an anthelmintic to treat several worm infestations. The plant is used to relief pain, and as a carminative, digestive and laxative. The bioactive component of the plant is Amentoflavone, a polyphenolic compound that is also present in many other plant families such as Selaginellaceae, Euphorbiaceae, Cupressaceae, Calophyllaceae and Podocarpaceae. ⁸⁰ So many studies on amentoflavone have proved its pharmacological potentials as antioxidant, anti-inflammatory, antifungal, and antivirus ^81,82 In a study carried out by Ryu et al., it was discovered that among the twelve compounds isolated from Torreya nucifera, amentoflavone showed potent activity on SARS-CoV by a molecular mechanism involving the inhibition of 3CLpro. ⁸³

Strobilanthes cusia

Strobilanthes cusia (Nees) Kuntzeis an herbaceous perennial plant, a member of the family Acanthaceae, widely distributed in Asia. ⁸⁴ It has no common name associated with it but in some Asian cities, it is called Assam indigo. The root and leaf extracts have been widely used in traditional herbal medicine thanks to its anti-inflammatory, antipyretic, antitumor, antimicrobial, and antiviral properties. ^85,86 The leaf and root extract possesses several bioactive compounds which include aurantiamide acetate, β-sitosterol, indirubin, tryptanthrin, betulin, indigodole B. ^87-89 These compounds exert antiviral activity against various viral infections. ^88,90 Tsai et al studied the antiviral activity of the bioactive compounds of the leaf extract of Strobilanthes cusia on human CoV-NL63. ⁹¹ They observed that among the compounds isolated, tryptanthrin displayed the strongest antiviral activity with significant reduction in human CoVs. The suggested mechanism of action of tryptanthrin is the moderation of viral RNA genome synthesis by its activity on viral enzymes like RNA-dependent RNA polymerase and PLpro that are responsible for the late stages of CoV-NL63 replication. ⁹¹

Veronica linariifolia

Veronica linariifolia Pall. ex Link. is a weed commonly called speedwell which belongs to the familyPlantaginaceae. There are several species of this genus including V. persica, V. liwanensis, V. filiformis, V. longifolia, V. fuhsi and V. peregrine. They are widely distributed in Australia, New Zealand, New Guinea and western Asia. This plant is used in traditional medicine for wound healing, and rheumatism, among various other diseases. Its various bioactive compounds possess a wide spectrum of activities like anti-inflammatory, antioxidant, antimicrobial and anticancer. ^92-94 The bioactive compounds of importance that have been isolated and investigated from Veronica linariifolia are linariifolioside, luteolin, apigenin, vanillic acid, protocatechuic acid, isoerulic acid and catechol. ^95,96 Luteolin is the most active of these compounds against viruses. It is a flavonoid active against SARS-CoV. Although Jo et al revealed that the anti-SARS CoV activity is mediated by inhibition of 3CLpro, ⁵¹ some other studies reported that this activity is exerted through inhibition of S-protein binding with ACE2. ^38,60

Camellia sinensis

Camellia sinensis (L.) Kuntze is an evergreen flowering small tree in the family Theaceae. It is commonly known as green tea. Green tea has many health benefits and has been in use for centuries for the treatment of several diseases and conditions, including vomiting, diarrhea, inflammation, infections, Parkinson’s disease, and cancers. Its use in the treatment of viral infection was reported in several studies. ^97-99 The bioactive component of Camellia sinensis that is active against CoVs is theaflavin, a polyphenolic compound. Yu et al and Chen et al reported that theaflavin from Camellia sinensis has a good anti-SARS CoV activity which is mediated by the inhibition of 3CLpro and RdRp. ^79,100 This observation was supported by a more recent study by Wu et al. ²⁴

Swertia kouitchensis

Swertia kouitchensis Franch. is a perennial plant distributed mainly in Southern China. It belongs to the family Gentianaceae and has no common names associated with it. It is widely used in traditional medicine to treat sore throat, indigestion and jaundice. The plant possesses several bioactive compounds, including xanthones, flavonoids, triterpenoids, alkaloids, which have been shown to be effective as anti-oxidant, antibacterial, antifungal, and antiviral. ^98,101,102 The bioactive compounds that inhibit 3CLpro, making them valuable against CoVs, are Kouitchenside and Oleanolic acid. ²⁴ Other species in Swertia genus with potential anti-SARS CoV activity include Swertia binchuanensis, Swertia macrosperma, Swertia maculate, Swertia mussotii.

Bupleurum spp

Bupleurum spp., also known as Saiko or Chai Hu, are annual or perennial herbs or shrubs of a large genus in the family Apiaceae native to North America and Southern Africa, and widely distributed in Asia. Some of the important species, that have been used in traditional medicine especially in China, Korea and Japan to treat fever, flu, cough, headache, asthma, chest pain, constipation, diarrhea, epilepsy, fatigue, and/or hepatitis, are Bupleurum chinenseDC, Bupleurum scorzoneerifolium, Bupleurum kaoi, Bupleurum falcatum. ¹⁰³ The main bioactive component of this plant is saikosaponin (a triterpene glycoside) which has been found to possess anti-cancer, antiviral, anti-inflammatory, antipyretic, antihepatotoxic, anti-allergic, immunoregulation, and neuroregulation activities. ^104,105 Saikosaponin is also present in some medicinal plants such as Heteromorpha spp., and Scrophularia scorodonia. ¹⁰⁶ Many studies have reported the antiviral activity of saikosaponin against CoVs by inhibition of viral attachment. ^106-108

Alnus japonica

Alnus japonica (Thunb.) Steud., known as Japanese alder, is a deciduous tree, a member of the family Betulaceae. It is found in Japan, Korea, Taiwan, eastern China, and Russia. The genus ‘Alnus’ iswell-known in Korean folk medicine and in Ayurvedic medicine for the treatment of hepatitis, mouth and throat inflammations, dysentery, stomach ache, diarrhea, fever, cancer. ^109,110 The dominant biologically active natural compounds of Alnus japonica is the diarylheptanoids. ¹¹¹ These secondary metabolites have also been isolated from other medicinal plants such as Curcuma kwangsiensis, Alpinia officinarum, Zingiber mekongense, Acer nikoense, Aframomummelegueta, Alpinia katsumadai, Acer nikoense. ¹¹² Diarylheptanoids exhibit anti-inflammatory, cytotoxic, antiviral and anticancer activities. ^113,114 Remarkably, diarylheptanoids from Alnus japonica have been found to be effective against SARS-CoV by inhibiting PLpro. ¹¹¹ Zang & Liu concluded that diarylheptanoids with other natural compounds could be used as alternative choices to fight SARS-COV-2. ¹¹⁵

Lonicera japonica

Lonicera japonica Thunb. also known as honeysuckleis a deciduous climber belonging to the family Caprifoliaceae native to eastern Asia. It is used widely in TCM and contained over 500 prescriptions listed in CP to treat conditions such as cough, cold, tonsillitis, fever, inflammation, pneumonia. ³¹ The plant extract consist of several constituents including organic acids and flavones that confers its wide pharmacological activities, such as hepatoprotective, anti-inflammatory, antioxidative, antibacterial, and antiviral activities. ¹¹⁶ The primary bioactive compound of the plant is chlorogenic acid, a phenolic acid that is active against viruses and other microorganisms. ¹¹⁷ Lonicera japonica has been extensively used to prevent and treat SARS-CoV by inhibiting RdRp involved in SARS-CoV replication. ^118,119 Indeed, it was the most popular plant used in the treatment of SARS epidemic of 2003 in China. ¹¹⁶ Also, “Shuang Huang Lian”, a TCM prescription, ¹²⁰ containing Lonicera japonica, exerted anti-SARS-CoV-2 activity. ³⁶

Aesculus chinensis

Aesculus chinensis Bunge, commonly called Chinese horse chestnut, abundantly distributed in northwestern China, is a deciduous tree species in the genus ‘Aesculus’ and a member of the Sapindaceae family. The seeds of this tree have been frequently used in folk medicine to treat chest and abdominal pain. ¹²¹ The bioactive constituent of Aesculus chinensis is escin, a triterpenoid saponin, which exerts pharmacological activities such as anti-inflammatory, antioxidative, anti-tumor and antimicrobial activity. ¹²² Escin was reported to possess antiviral activity against SARS-CoV by inhibiting viral 3CLpro. ^118,123

Saposhnikovia divaricata

Saposhnikovia divaricata (Turcz.) Schischk., commonly called Siler, is an herbaceous perennial plant that belongs to the family Apiaceae. The plant is native to China, Russia, Korea and Japan, and is used as herbal medicine for the treatment of general body pain, headaches, spasm, tremor, arthritis and inflammation. ^124,125 The plant possesses several bioactive compounds including coumarins, chromones, lignans, sterols that elicit antioxidative, antimicrobial, anti-inflammatory, immunoregulatory, anti-proliferative, and analgesic activities. ^126,127 The compound that is effective against viruses are the coumarins. ^126,128 Coumarins from the root of Saposhnikoviae divaricate is one of the constituents of a TCM formula, named “Yuping feng” powder used to prevent SARS-CoV. ¹²⁹ Liu et al showed that Saposhnikovia divaricate is contained in some of the Chinese herbal prescriptions recommended by the Chinese government in 2004 for the treatment of SARS-CoV infection. ¹³⁰ Further, Yang et al listed it as one of the frequently used medicinal herbs in the prevention of COVID-19 infection. ³⁶ Also, Saposhnikovia divaricata has been shown to be effective against porcine epidemic diarrhea virus, which belongs to the same class (Coronaviridae) with SARS and MERS viruses, by a molecular mechanism involving the inhibition of S-protein. ^118,128

Discussion and Conclusion

Undeniably, plants are great reservoir of compounds valuable for the treatment of infections and other disease conditions. ¹³¹ Importantly, medicinal plants offer some advantages, such as ease of accessibility and availability, as well as low toxicity over synthetic drugs. Twenty medicinal plants with various bioactive compounds that possess potentials for inhibition of SARS-CoV-2 were identified in this review (Table 1). The phytochemical class among these bioactive compounds varied from diterpenoid, anthraquinones, saponin, flavonoid, tannin, alkaloids and steroids, with flavonoids being the prominent class. The mechanism of the antiviral action of these compounds varies, but involved the inhibition of at least one enzyme associated with the coronavirus pathogenesis, i.e. S-protein, which initiates the entry of the virus by binding to host ACE2, ¹³² 3CLpro and PLpro, which are both responsible for the cleavage of the polyprotein translated from the viral RNA, ^10,11,133 and RdRp, that catalyzes the synthesis of RNA enzyme. ¹³⁴ Many researchers have posited that bioactive compounds with inhibitory activity against SARS-CoV may be active against SARS-CoV-2 because of some similarities they share. ¹³⁵ Indeed, they are both beta-coronaviruses with similar genome sequencing and life cycle, albeit their origin may differ. The mode of entry into a host, the RNA replication, ^132,136 as well asthe mode of transmission from person-to-person and clinical manifestations of the disease from both viruses are also similar, hence the name SARS-CoV and SARS-CoV-2. Several studies have reported that medicinal plant used in the treatment of SARS-CoV may offer some sort of relief from the burden of COVID-19 pandemic. ¹¹⁵ None of the isolated compounds from the medicinal plants have been successfully tried clinically for the treatment of COVID-19. However, several drug developments, formulation processes, pilot test and clinical trials are under way. ^25,36,137

Since coronavirus pathogenesis involves some specific enzymes at different stages of the development of COVID-19 disease, a combination of plant extracts, pure bioactive phytocompounds, or plants themselves described in this review article, such as Alnus japonica, Andrographis paniculata, Glycyrrhiza glabra, Lonicera japonica, Saposhnikovia divaricata, and Veronica linariifolia, may be beneficial and used in clinical trials for the management of COVID-19. However, safety and compatibility of this combination must be ensured.

In conclusion, several evidences have been highlighted in this review indicating that medicinal plant used in the treatment of SARS-CoV could be useful in the management of COVID-19. The search for medicinal plants with inhibitory bioactive compounds that may be developed into various drug delivery systems against coronavirus could be the long awaited breakthrough scientist have been searching to change the narratives of COVID-19 pandemic since there is no effective cure yet.

Ethical Issues

Not applicable.

Conflict of Interest

The authors declare no conflicts of interest.

References

1. Abolaji AO, Adebayo HA, Odesanmi OS. Nutritional qualities of three medicinal plant parts (Xylopia aethiopica, Blighia sapida and Parinari polyandra) commonly used by pregnant women in the western part of Nigeria. Pak J Nutr 2007; 6(6):655-8. doi: 10.3923/pjn.2007.665.668 [Crossref]
2. Alamgir AN. Therapeutic use of medicinal plants and their extracts In: Progress in Drug Research. Springer International Publishing 2017. doi: 10.1007/978-3-319-63862-1 [Crossref]
3. Sofowora A, Ogunbodede E, Onayade A. The role and place of medicinal plants in the strategies for disease prevention. Afr J Tradit Complement Altern Med 2013; 10(5):210-29. doi: 10.4314/ajtcam.v10i5.2 [Crossref]
4. Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 2016; 79(3):629-61. doi: 10.1021/acs.jnatprod.5b01055 [Crossref]
5. Cragg GM, Newman DJ. Natural products: a continuing source of novel drug leads. Biochim Biophys Acta 2013; 1830(6):3670-95. doi: 10.1016/j.bbagen.2013.02.008 [Crossref]
6. Ovadje P, Roma A, Steckle M, Nicoletti L, Arnason JT, Pandey S. Advances in the research and development of natural health products as main stream cancer therapeutics. Evid Based Complement Alternat Med 2015; 2015:751348. doi: 10.1155/2015/751348 [Crossref]
7. Robinson MM, Zhang X. The World Medicines Situation 2011, Traditional Medicines: Global Situation, Issues and Challenges. Geneva: WHO; 2011.
8. Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol 2016; 24(6):490-502. doi: 10.1016/j.tim.2016.03.003 [Crossref]
9. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019; 17(3):181-92. doi: 10.1038/s41579-018-0118-9 [Crossref]
10. Harcourt BH, Jukneliene D, Kanjanahaluethai A, Bechill J, Severson KM, Smith CM. Identification of severe acute respiratory syndrome coronavirus replicase products and characterization of papain-like protease activity. J Virol 2004; 78(24):13600-12. doi: 10.1128/jvi.78.24.13600-13612.2004 [Crossref]
11. Tahir Ul Qamar M, Alqahtani SM, Alamri MA, Chen LL. Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. J Pharm Anal 2020; 10(4):313-9. doi: 10.1016/j.jpha.2020.03.009 [Crossref]
12. Li H, Wang Y, Ji M, Pei F, Zhao Q, Zhou Y. Transmission routes analysis of SARS-CoV-2: a systematic review and case report. Front Cell Dev Biol 2020; 8:618. doi: 10.3389/fcell.2020.00618 [Crossref]
13. Cheng PK, Wong DA, Tong LK, Ip SM, Lo AC, Lau CS. Viral shedding patterns of coronavirus in patients with probable severe acute respiratory syndrome. Lancet 2004; 363(9422):1699-700. doi: 10.1016/s0140-6736(04)16255-7 [Crossref]
14. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 382(8):727-33. doi: 10.1056/NEJMoa2001017 [Crossref]
15. Bradburne AF, Bynoe ML, Tyrrell DA. Effects of a “new” human respiratory virus in volunteers. Br Med J 1967; 3(5568):767-9. doi: 10.1136/bmj.3.5568.767 [Crossref]
16. Hamre D, Procknow JJ. A new virus isolated from the human respiratory tract. Proc Soc Exp Biol Med 1966; 121(1):190-3. doi: 10.3181/00379727-121-30734 [Crossref]
17. Woo PC, Lau SK, Chu CM, Chan KH, Tsoi HW, Huang Y. Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. J Virol 2005; 79(2):884-95. doi: 10.1128/jvi.79.2.884-895.2005 [Crossref]
18. Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol 2015; 1282:1-23. doi: 10.1007/978-1-4939-2438-7_1 [Crossref]
19. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223):497-506. doi: 10.1016/s0140-6736(20)30183-5 [Crossref]
20. Coronavirus Disease (COVID-2019) Situation Reports 89; World Health Organization, 2020. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports.
21. Chao WW, Lin BF. Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian). Chin Med 2010; 5:17. doi: 10.1186/1749-8546-5-17 [Crossref]
22. Adeleye OA, Babalola CO, Femi-Oyewo MN, Balogun GY. Antimicrobial activity and stability of Andrographis paniculata cream containing shea butter. Niger J Pharm Res 2019; 15(1):9-18.
23. Gupta S, Mishra KP, Ganju L. Broad-spectrum antiviral properties of andrographolide. Arch Virol 2017; 162(3):611-23. doi: 10.1007/s00705-016-3166-3 [Crossref]
24. Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B 2020; 10(5):766-88. doi: 10.1016/j.apsb.2020.02.008 [Crossref]
25. Rosa SGV, Santos WC. Clinical trials on drug repositioning for COVID-19 treatment. Rev Panam Salud Publica 2020; 44:e40. doi: 10.26633/rpsp.2020.40 [Crossref]
26. Yang QW, Li Q, Zhang J, Xu Q, Yang X, Li ZY. Crystal structure and anti-inflammatory and anaphylactic effects of andrographlide sulphonate E in Xiyanping, a traditional Chinese medicine injection. J Pharm Pharmacol 2019; 71(2):251-9. doi: 10.1111/jphp.13028 [Crossref]
27. Luo Y, Wang CZ, Hesse-Fong J, Lin JG, Yuan CS. Application of Chinese medicine in acute and critical medical conditions. Am J Chin Med 2019; 47(6):1223-35. doi: 10.1142/s0192415x19500629 [Crossref]
28. Ho TY, Wu SL, Chen JC, Li CC, Hsiang CY. Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Res 2007; 74(2):92-101. doi: 10.1016/j.antiviral.2006.04.014 [Crossref]
29. Luo W, Su X, Gong S, Qin Y, Liu W, Li J. Anti-SARS coronavirus 3C-like protease effects of Rheum palmatum L extracts. Biosci Trends 2009; 3(4):124-6.
30. Schwarz S, Wang K, Yu W, Sun B, Schwarz W. Emodin inhibits current through SARS-associated coronavirus 3a protein. Antiviral Res 2011; 90(1):64-9. doi: 10.1016/j.antiviral.2011.02.008 [Crossref]
31. Pharmacopoeia of the People’s Republic of China (PPRC). China: Chemical Industry Press; 2010. p. 22-3.
32. Zuo GY, Wang GC, Zhao YB, Xu GL, Hao XY, Han J. Screening of Chinese medicinal plants for inhibition against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). J Ethnopharmacol 2008; 120(2):287-90. doi: 10.1016/j.jep.2008.08.021 [Crossref]
33. Lin HW, Sun MX, Wang YH, Yang LM, Yang YR, Huang N. Anti-HIV activities of the compounds isolated from Polygonum cuspidatum and Polygonum multiflorum. Planta Med 2010; 76(9):889-92. doi: 10.1055/s-0029-1240796 [Crossref]
34. Bounda GA, Feng YU. Review of clinical studies of Polygonum multiflorum Thunb and its isolated bioactive compounds. Pharmacognosy Res 2015; 7(3):225-36. doi: 10.4103/0974-8490.157957 [Crossref]
35. Yarnell E. Herbs for emerging viral infectious diseases. Altern Complement Ther 2016; 22(4):164-74. doi: 10.1089/act.2016.29062.eya [Crossref]
36. Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective. Int J Biol Sci 2020; 16(10):1708-17. doi: 10.7150/ijbs.45538 [Crossref]
37. Pilcher H. Liquorice may tackle SARS. Nature 2003. doi: 10.1038/news030609-16 [Crossref]
38. Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet 2003; 361(9374):2045-6. doi: 10.1016/s0140-6736(03)13615-x [Crossref]
39. Hoever G, Baltina L, Michaelis M, Kondratenko R, Baltina L, Tolstikov GA. Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus. J Med Chem 2005; 48(4):1256-9. doi: 10.1021/jm0493008 [Crossref]
40. Fiore C, Eisenhut M, Krausse R, Ragazzi E, Pellati D, Armanini D. Antiviral effects of Glycyrrhiza species. Phytother Res 2008; 22(2):141-8. doi: 10.1002/ptr.2295 [Crossref]
41. Shang X, He X, He X, Li M, Zhang R, Fan P. The genus Scutellaria an ethnopharmacological and phytochemical review. J Ethnopharmacol 2010; 128(2):279-313. doi: 10.1016/j.jep.2010.01.006 [Crossref]
42. Zhao Q, Chen XY, Martin C. Scutellaria baicalensis, the golden herb from the garden of Chinese medicinal plants. Sci Bull (Beijing) 2016; 61(18):1391-8. doi: 10.1007/s11434-016-1136-5 [Crossref]
43. Guo X, Wang X, Su W, Zhang G, Zhou R. DNA barcodes for discriminating the medicinal plant Scutellaria baicalensis (Lamiaceae) and its adulterants. Biol Pharm Bull 2011; 34(8):1198-203. doi: 10.1248/bpb.34.1198 [Crossref]
44. Parajuli P, Joshee N, Rimando AM, Mittal S, Yadav AK. In vitro antitumor mechanisms of various Scutellaria extracts and constituent flavonoids. Planta Med 2009; 75(1):41-8. doi: 10.1055/s-0028-1088364 [Crossref]
45. Chen F, Chan KH, Jiang Y, Kao RY, Lu HT, Fan KW. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol 2004; 31(1):69-75. doi: 10.1016/j.jcv.2004.03.003 [Crossref]
46. Wong SS, Yuen KY. The management of coronavirus infections with particular reference to SARS. J Antimicrob Chemother 2008; 62(3):437-41. doi: 10.1093/jac/dkn243 [Crossref]
47. Bischoff SC. Quercetin: potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Care 2008; 11(6):733-40. doi: 10.1097/MCO.0b013e32831394b8 [Crossref]
48. Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: a bioactive flavonoid. Pharmacogn Rev 2016; 10(20):84-9. doi: 10.4103/0973-7847.194044 [Crossref]
49. Smith M, Smith JC. Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface. ChemRxiv Preprint 2020. doi: 10.26434/chemrxiv.11871402.v3 [Crossref]
50. Nguyen TT, Woo HJ, Kang HK, Nguyen VD, Kim YM, Kim DW. Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris. Biotechnol Lett 2012; 34(5):831-8. doi: 10.1007/s10529-011-0845-8 [Crossref]
51. Jo S, Kim S, Shin DH, Kim MS. Inhibition of SARS-CoV 3CL protease by flavonoids. J Enzyme Inhib Med Chem 2020; 35(1):145-51. doi: 10.1080/14756366.2019.1690480 [Crossref]
52. Jucá MM, Cysne Filho FMS, de Almeida JC, da Silva Mesquita D, de Moraes Barriga JR, Dias KCF. Flavonoids: biological activities and therapeutic potential. Nat Prod Res 2020; 34(5):692-705. doi: 10.1080/14786419.2018.1493588 [Crossref]
53. Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol 2017; 162(9):2539-51. doi: 10.1007/s00705-017-3417-y [Crossref]
54. Chen CJ, Michaelis M, Hsu HK, Tsai CC, Yang KD, Wu YC. Toona sinensis Roem tender leaf extract inhibits SARS coronavirus replication. J Ethnopharmacol 2008; 120(1):108-11. doi: 10.1016/j.jep.2008.07.048 [Crossref]
55. Peng W, Liu Y, Hu M, Zhang M, Yang J, Liang F. Toona sinensis: a comprehensive review on its traditional usages, phytochemisty, pharmacology and toxicology. Rev Bras Farmacogn 2019; 29(1):111-24. doi: 10.1016/j.bjp.2018.07.009 [Crossref]
56. Singh YD, Jena B, Ningthoujam R, Panda S, Priyadarsini P, Pattanayak S. Potential bioactive molecules from natural products to combat against coronavirus. Adv Tradit Med 2020:1-12. doi: 10.1007/s13596-020-00496-w [Crossref]
57. Lau KM, Lee KM, Koon CM, Cheung CS, Lau CP, Ho HM. Immunomodulatory and anti-SARS activities of Houttuynia cordata. J Ethnopharmacol 2008; 118(1):79-85. doi: 10.1016/j.jep.2008.03.018 [Crossref]
58. Młynarczyk K, Walkowiak-Tomczak D, Łysiak GP. Bioactive properties of Sambucus nigra L as a functional ingredient for food and pharmaceutical industry. J Funct Foods 2018; 40:377-90. doi: 10.1016/j.jff.2017.11.025 [Crossref]
59. Djakpo O, Yao W. Rhus chinensis and Galla chinensis--folklore to modern evidence: review. Phytother Res 2010; 24(12):1739-47. doi: 10.1002/ptr.3215 [Crossref]
60. Yi L, Li Z, Yuan K, Qu X, Chen J, Wang G. Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells. J Virol 2004; 78(20):11334-9. doi: 10.1128/jvi.78.20.11334-11339.2004 [Crossref]
61. Bhat HP, Jakribettu RP, Boloor R, Fayad R, Baliga MS. Use of ayurvedic medicinal plants as immunomodulators in geriatrics: preclinical studies. In: Watson RR, ed. Foods and Dietary Supplements in the Prevention and Treatment of Disease in Older Adults. Massachusetts: Academic Press; 2015. p. 143-9. 10.1016/b978-0-12-418680-4.00015-4
62. Lv JJ, Wang YF, Zhang JM, Yu S, Wang D, Zhu HT. Anti-hepatitis B virus activities and absolute configurations of sesquiterpenoid glycosides from Phyllanthus emblica. Org Biomol Chem 2014; 12(43):8764-74. doi: 10.1039/c4ob01196a [Crossref]
63. Yadav SS, Singh MK, Singh PK, Kumar V. Traditional knowledge to clinical trials: a review on therapeutic actions of Emblica officinalis. Biomed Pharmacother 2017; 93:1292-302. doi: 10.1016/j.biopha.2017.07.065 [Crossref]
64. Fazil M, Nikhat S. Nutraceutical and pharmacological appraisal of Āmla (Emblica officinalis Gaertn): a review. Eur J Med Plants 2019; 30(3):1-13. doi: 10.9734/ejmp/2019/v30i330176 [Crossref]
65. Ahmad W, Ejaz S, Anwar K, Ashraf M. Exploration of the in vitro cytotoxic and antiviral activities of different medicinal plants against infectious bursal disease (IBD) virus. Cent Eur J Biol 2014; 9(5):531-42. doi: 10.2478/s11535-013-0276-8 [Crossref]
66. Xiang YF, Ju HQ, Li S, Zhang YJ, Yang CR, Wang YF. Effects of 1,2,4,6-tetra-O-galloyl-β-D-glucose from P emblica on HBsAg and HBeAg secretion in HepG2215 cell culture. Virol Sin 2010; 25(5):375-80. doi: 10.1007/s12250-010-3144-y [Crossref]
67. Zhou Y, Kang L, Liao S, Pan Q, Ge X, Li Z. Transcriptomic analysis reveals differential gene expressions for cell growth and functional secondary metabolites in induced autotetraploid of Chinese woad (Isatis indigotica Fort). PLoS One 2015; 10(3):e0116392. doi: 10.1371/journal.pone.0116392 [Crossref]
68. Kang M, Wu H, Yang Q, Huang L, Hu Q, Ma T. A chromosome-scale genome assembly of Isatis indigotica, an important medicinal plant used in traditional Chinese medicine: an Isatis genome. Hortic Res 2020; 7:18. doi: 10.1038/s41438-020-0240-5 [Crossref]
69. Lin CW, Tsai FJ, Tsai CH, Lai CC, Wan L, Ho TY. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. Antiviral Res 2005; 68(1):36-42. doi: 10.1016/j.antiviral.2005.07.002 [Crossref]
70. Hsuan SL, Chang SC, Wang SY, Liao TL, Jong TT, Chien MS. The cytotoxicity to leukemia cells and antiviral effects of Isatis indigotica extracts on pseudorabies virus. J Ethnopharmacol 2009; 123(1):61-7. doi: 10.1016/j.jep.2009.02.028 [Crossref]
71. Yang Z, Wang Y, Zhong S, Zhao S, Zeng X, Mo Z. In vitro inhibition of influenza virus infection by a crude extract from Isatis indigotica root resulting in the prevention of viral attachment. Mol Med Rep 2012; 5(3):793-9. doi: 10.3892/mmr.2011.709 [Crossref]
72. Xiao P, Ye W, Chen J, Li X. [Antiviral activities against influenza virus (FM1) of bioactive fractions and representative compounds extracted from Banlangen (Radix isatidis)]. J Tradit Chin Med 2016; 36(3):369-76. doi: 10.1016/s0254-6272(16)30051-6 [Crossref]
73. Su JH, Diao RG, Lv SG, Mou XD, Li K. Modes of antiviral action of chemical portions and constituents from woad root extract against influenza virus A FM1. Evid Based Complement Alternat Med 2016; 2016:2537294. doi: 10.1155/2016/2537294 [Crossref]
74. Ye WY, Li X, Cheng JW. Screening of eleven chemical constituents from Radix isatidis for antiviral activity. Afr J Pharm Pharmacol 2011; 5(16):1932-6. doi: 10.5897/ajpp11.559 [Crossref]
75. De Clercq E. Potential antivirals and antiviral strategies against SARS coronavirus infections. Expert Rev Anti Infect Ther 2006; 4(2):291-302. doi: 10.1586/14787210.4.2.291 [Crossref]
76. Liu Y, Jing YY, Zeng CY, Li CG, Xu LH, Yan L. Scutellarin suppresses NLRP3 inflammasome activation in macrophages and protects mice against bacterial sepsis. Front Pharmacol 2017; 8:975. doi: 10.3389/fphar.2017.00975 [Crossref]
77. Wang L, Ma Q. Clinical benefits and pharmacology of scutellarin: a comprehensive review. Pharmacol Ther 2018; 190:105-27. doi: 10.1016/j.pharmthera.2018.05.006 [Crossref]
78. Liu Y, Wang J, Zhang X, Wang L, Hao T, Cheng Y. Scutellarin exerts hypoglycemic and renal protective effects in db/db mice via the Nrf2/HO-1 signaling pathway. Oxid Med Cell Longev 2019; 2019:1354345. doi: 10.1155/2019/1354345 [Crossref]
79. Yu MS, Lee J, Lee JM, Kim Y, Chin YW, Jee JG. Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13. Bioorg Med Chem Lett 2012; 22(12):4049-54. doi: 10.1016/j.bmcl.2012.04.081 [Crossref]
80. Yu S, Yan H, Zhang L, Shan M, Chen P, Ding A. A review on the phytochemistry, pharmacology, and pharmacokinetics of amentoflavone, a naturally-occurring biflavonoid. Molecules 2017; 22(2):229. doi: 10.3390/molecules22020299 [Crossref]
81. Zhang Z, Sun T, Niu JG, He ZQ, Liu Y, Wang F. Amentoflavone protects hippocampal neurons: anti-inflammatory, antioxidative, and antiapoptotic effects. Neural Regen Res 2015; 10(7):1125-33. doi: 10.4103/1673-5374.160109 [Crossref]
82. An J, Li Z, Dong Y, Ren J, Huo J. Amentoflavone protects against psoriasis-like skin lesion through suppression of NF-κB-mediated inflammation and keratinocyte proliferation. Mol Cell Biochem 2016; 413(1-2):87-95. doi: 10.1007/s11010-015-2641-6 [Crossref]
83. Ryu YB, Jeong HJ, Kim JH, Kim YM, Park JY, Kim D. Biflavonoids from Torreya nucifera displaying SARS-CoV 3CLpro inhibition. Bioorg Med Chem 2010; 18(22):7940-7. doi: 10.1016/j.bmc.2010.09.035 [Crossref]
84. Lin W, Huang W, Ning S, Wang X, Ye Q, Wei D. De novo characterization of the Baphicacanthus cusia (Nees) Bremek transcriptome and analysis of candidate genes involved in indican biosynthesis and metabolism. PLoS One 2018; 13(7):e0199788. doi: 10.1371/journal.pone.0199788 [Crossref]
85. Ichimaru Y, Saito H, Uchiyama T, Metori K, Tabata K, Suzuki T. Indirubin 3’-(O-oxiran-2-ylmethyl)oxime: a novel anticancer agent. Bioorg Med Chem Lett 2015; 25(7):1403-6. doi: 10.1016/j.bmcl.2015.02.053 [Crossref]
86. Chen H, Shao J, Zhang H, Jiang M, Huang L, Zhang Z. Sequencing and analysis of Strobilanthes cusia (Nees) Kuntze chloroplast genome revealed the rare simultaneous contraction and expansion of the inverted repeat region in angiosperm. Front Plant Sci 2018; 9:324. doi: 10.3389/fpls.2018.00324 [Crossref]
87. Gu W, Zhang Y, Hao XJ, Yang FM, Sun QY, Morris-Natschke SL. Indole alkaloid glycosides from the aerial parts of Strobilanthes cusia. J Nat Prod 2014; 77(12):2590-4. doi: 10.1021/np5003274 [Crossref]
88. Zhou B, Yang Z, Feng Q, Liang X, Li J, Zanin M. Aurantiamide acetate from Baphicacanthus cusia root exhibits anti-inflammatory and anti-viral effects via inhibition of the NF-κB signaling pathway in influenza A virus-infected cells. J Ethnopharmacol 2017; 199:60-7. doi: 10.1016/j.jep.2017.01.038 [Crossref]
89. Lee CL, Wang CM, Hu HC, Yen HR, Song YC, Yu SJ. Indole alkaloids indigodoles A-C from aerial parts of Strobilanthes cusia in the traditional Chinese medicine Qing Dai have anti-IL-17 properties. Phytochemistry 2019; 162:39-46. doi: 10.1016/j.phytochem.2019.02.016 [Crossref]
90. Gu W, Wang W, Li XN, Zhang Y, Wang LP, Yuan CM. A novel isocoumarin with anti-influenza virus activity from Strobilanthes cusia. Fitoterapia 2015; 107:60-2. doi: 10.1016/j.fitote.2015.10.009 [Crossref]
91. Tsai YC, Lee CL, Yen HR, Chang YS, Lin YP, Huang SH. Antiviral action of tryptanthrin isolated from Strobilanthes cusia leaf against human coronavirus NL63. Biomolecules 2020; 10(3):366. doi: 10.3390/biom10030366 [Crossref]
92. Dunkić V, Kosalec I, Kosir IJ, Potocnik T, Cerenak A, Koncic MZ. Antioxidant and antimicrobial properties of Veronica spicata L (Plantaginaceae). Curr Drug Targets 2015; 16(14):1660-70. doi: 10.2174/1389450116666150531161820 [Crossref]
93. Sharifi-Rad J, Iriti M, Setzer WN, Sharifi-Rad M, Roointan A, Salehi B. Antiviral activity of Veronica persica Poir on herpes virus infection. Cell Mol Biol (Noisy-le-grand) 2018; 64(8):11-7. doi: 10.14715/cmb/2018.64.8.2 [Crossref]
94. Sharifi-Rad J, Tayeboon GS, Niknam F, Sharifi-Rad M, Mohajeri M, Salehi B. Veronica persica Poir extract - antibacterial, antifungal and scolicidal activities, and inhibitory potential on acetylcholinesterase, tyrosinase, lipoxygenase and xanthine oxidase. Cell Mol Biol (Noisy-le-grand) 2018; 64(8):50-6. doi: 10.14715/cmb/2018.64.8.8 [Crossref]
95. Xue H, Chen KX, Zhang LQ, Li YM. Review of the ethnopharmacology, phytochemistry, and pharmacology of the genus Veronica. Am J Chin Med 2019; 47(6):1193-221. doi: 10.1142/s0192415x19500617 [Crossref]
96. Salehi B, Shivaprasad Shetty M, N VAK, Živković J, Calina D, Oana Docea A. Veronica plants-drifting from farm to traditional healing, food application, and phytopharmacology. Molecules 2019; 24(13):2454. doi: 10.3390/molecules24132454 [Crossref]
97. Ciesek S, von Hahn T, Colpitts CC, Schang LM, Friesland M, Steinmann J. The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry. Hepatology 2011; 54(6):1947-55. doi: 10.1002/hep.24610 [Crossref]
98. Chattopadhyay D, Mukherjee H, Bag P, Ghosh S, Samanta A, Chakrabarti S. Ethnomedicines in antiviral drug discovery. Int J Biomed Pharm Sci 2009; 3(1):1-25.
99. Mahmood MS, Mártinez JL, Aslam A, Rafique A, Vinet R, Laurido C. Antiviral effects of green tea (Camellia sinensis) against pathogenic viruses in human and animals (a mini-review). Afr J Tradit Complement Altern Med 2016; 13(2):176. doi: 10.4314/ajtcam.v13i2.21 [Crossref]
100. Chen CN, Lin CP, Huang KK, Chen WC, Hsieh HP, Liang PH. Inhibition of SARS-CoV 3C-like protease activity by theaflavin-3,3’-digallate (TF3). Evid Based Complement Alternat Med 2005; 2(2):209-15. doi: 10.1093/ecam/neh081 [Crossref]
101. Ruan J, Zheng C, Liu Y, Qu L, Yu H, Han L. Chemical and biological research on herbal medicines rich in xanthones. Molecules 2017; 22(10):1698. doi: 10.3390/molecules22101698 [Crossref]
102. Geng CA, Chen JJ. The progress of anti-HBV constituents from medicinal plants in China. Nat Prod Bioprospect 2018; 8(4):227-44. doi: 10.1007/s13659-018-0178-6 [Crossref]
103. Yang F, Dong X, Yin X, Wang W, You L, Ni J. Radix Bupleuri: a review of traditional uses, botany, phytochemistry, pharmacology, and toxicology. Biomed Res Int 2017; 2017:7597596. doi: 10.1155/2017/7597596 [Crossref]
104. Yuan B, Yang R, Ma Y, Zhou S, Zhang X, Liu Y. A systematic review of the active saikosaponins and extracts isolated from Radix Bupleuri and their applications. Pharm Biol 2017; 55(1):620-35. doi: 10.1080/13880209.2016.1262433 [Crossref]
105. Kim BM. The role of saikosaponins in therapeutic strategies for age-related diseases. Oxid Med Cell Longev 2018; 2018:8275256. doi: 10.1155/2018/8275256 [Crossref]
106. Sinha SK, Shakya A, Prasad SK, Singh S, Gurav NS, Prasad RS. An in-silico evaluation of different saikosaponins for their potency against SARS-CoV-2 using NSP15 and fusion spike glycoprotein as targets. J Biomol Struct Dyn 2021; 39(9):3244-55. doi: 10.1080/07391102.2020.1762741 [Crossref]
107. Lin LT, Hsu WC, Lin CC. Antiviral natural products and herbal medicines. J Tradit Complement Med 2014; 4(1):24-35. doi: 10.4103/2225-4110.124335 [Crossref]
108. Liu CX. Pay attention to situation of SARS-CoV-2 and TCM advantages in treatment of novel coronavirus infection. Chin Herb Med 2020; 12(2):97-103. doi: 10.1016/j.chmed.2020.03.004 [Crossref]
109. Kim ST, Kim JD, Ahn SH, Ahn GS, Lee YI, Jeong YS. Hepatoprotective and antioxidant effects of Alnus japonica extracts on acetaminophen-induced hepatotoxicity in rats. Phytother Res 2004; 18(12):971-5. doi: 10.1002/ptr.1540 [Crossref]
110. Sati SC, Sati N, Sati OP. Bioactive constituents and medicinal importance of genus Alnus. Pharmacogn Rev 2011; 5(10):174-83. doi: 10.4103/0973-7847.91115 [Crossref]
111. Park JY, Jeong HJ, Kim JH, Kim YM, Park SJ, Kim D. Diarylheptanoids from Alnus japonica inhibit papain-like protease of severe acute respiratory syndrome coronavirus. Biol Pharm Bull 2012; 35(11):2036-42. doi: 10.1248/bpb.b12-00623 [Crossref]
112. Motiur Rahman AFM, Lu Y, Lee HJ, Jo H, Yin W, Alam MS. Linear diarylheptanoids as potential anticancer therapeutics: synthesis, biological evaluation, and structure-activity relationship studies. Arch Pharm Res 2018; 41(12):1131-48. doi: 10.1007/s12272-018-1004-8 [Crossref]
113. An N, Zhang HW, Xu LZ, Yang SL, Zou ZM. New diarylheptanoids from the rhizome of Alpinia officinarum Hance. Food Chem 2010; 119(2):513-7. doi: 10.1016/j.foodchem.2009.06.046 [Crossref]
114. Sun Y, Kurokawa M, Miura M, Kakegawa T, Motohashi S, Yasukawa K. Bioactivity and synthesis of diarylheptanoids from Alpinia officinarum. Stud Nat Prod Chem 2016; 49:157-87. doi: 10.1016/b978-0-444-63601-0.00004-1 [Crossref]
115. Zhang L, Liu Y. Potential interventions for novel coronavirus in China: a systematic review. J Med Virol 2020; 92(5):479-90. doi: 10.1002/jmv.25707 [Crossref]
116. Shang X, Pan H, Li M, Miao X, Ding H. Lonicera japonica Thunb: ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine. J Ethnopharmacol 2011; 138(1):1-21. doi: 10.1016/j.jep.2011.08.016 [Crossref]
117. Ding Y, Cao Z, Cao L, Ding G, Wang Z, Xiao W. Antiviral activity of chlorogenic acid against influenza A (H1N1/H3N2) virus and its inhibition of neuraminidase. Sci Rep 2017; 7:45723. doi: 10.1038/srep45723 [Crossref]
118. Wu CY, Jan JT, Ma SH, Kuo CJ, Juan HF, Cheng YS. Small molecules targeting severe acute respiratory syndrome human coronavirus. Proc Natl Acad Sci U S A 2004; 101(27):10012-7. doi: 10.1073/pnas.0403596101 [Crossref]
119. Liu B, Zhou J. SARS-CoV protease inhibitors design using virtual screening method from natural products libraries. J Comput Chem 2005; 26(5):484-90. doi: 10.1002/jcc.20186 [Crossref]
120. Gao Y, Fang L, Cai R, Zong C, Chen X, Lu J. Shuang-Huang-Lian exerts anti-inflammatory and anti-oxidative activities in lipopolysaccharide-stimulated murine alveolar macrophages. Phytomedicine 2014; 21(4):461-9. doi: 10.1016/j.phymed.2013.09.022 [Crossref]
121. Zhang N, Wei S, Cao S, Zhang Q, Kang N, Ding L. Bioactive triterpenoid saponins from the seeds of Aesculus chinensis Bge var chekiangensis. Front Chem 2019; 7:908. doi: 10.3389/fchem.2019.00908 [Crossref]
122. Cheng JT, Chen ST, Guo C, Jiao MJ, Cui WJ, Wang SH. Triterpenoid saponins from the seeds of Aesculus chinensis and their cytotoxicities. Nat Prod Bioprospect 2018; 8(1):47-56. doi: 10.1007/s13659-017-0148-4 [Crossref]
123. Kim JW, Ha TK, Cho H, Kim E, Shim SH, Yang JL. Antiviral escin derivatives from the seeds of Aesculus turbinata Blume (Japanese horse chestnut). Bioorg Med Chem Lett 2017; 27(13):3019-25. doi: 10.1016/j.bmcl.2017.05.022 [Crossref]
124. Yang M, Wang CC, Wang WL, Xu JP, Wang J, Zhang CH. Saposhnikovia divaricata-an ethnopharmacological, phytochemical and pharmacological review. Chin J Integr Med 2020; 26(11):873-80. doi: 10.1007/s11655-020-3091-x [Crossref]
125. Kong X, Liu C, Zhang C, Zhao J, Wang J, Wan H. The suppressive effects of Saposhnikovia divaricata (Fangfeng) chromone extract on rheumatoid arthritis via inhibition of nuclear factor-κB and mitogen activated proteinkinases activation on collagen-induced arthritis model. J Ethnopharmacol 2013; 148(3):842-50. doi: 10.1016/j.jep.2013.05.023 [Crossref]
126. Yang JL, Dhodary B, Quy Ha TK, Kim J, Kim E, Oh WK. Three new coumarins from Saposhnikovia divaricata and their porcine epidemic diarrhea virus (PEDV) inhibitory activity. Tetrahedron 2015; 71(28):4651-8. doi: 10.1016/j.tet.2015.04.092 [Crossref]
127. Kim M, Seo KS, Yun KW. Antimicrobial and antioxidant activity of Saposhnikovia divaricata, Peucedanum japonicum and Glehnia littoralis. Indian J Pharm Sci 2018; 80(3):560-5. doi: 10.4172/pharmaceutical-sciences.1000393 [Crossref]
128. Yang JL, Ha TK, Oh WK. Discovery of inhibitory materials against PEDV corona virus from medicinal plants. Jpn J Vet Res 2016; 64(Suppl 1):S53-S63. doi: 10.14943/jjvr.64.suppl.s53 [Crossref]
129. Lau JT, Leung PC, Wong EL, Fong C, Cheng KF, Zhang SC. The use of an herbal formula by hospital care workers during the severe acute respiratory syndrome epidemic in Hong Kong to prevent severe acute respiratory syndrome transmission, relieve influenza-related symptoms, and improve quality of life: a prospective cohort study. J Altern Complement Med 2005; 11(1):49-55. doi: 10.1089/acm.2005.11.49 [Crossref]
130. Liu Q, Zhou YH, Ye F, Yang ZQ. Antivirals for respiratory viral infections: problems and prospects. Semin Respir Crit Care Med 2016; 37(4):640-6. doi: 10.1055/s-0036-1584803 [Crossref]
131. Chugh NA, Bali S, Koul A. Integration of botanicals in contemporary medicine: road blocks, checkpoints and go-ahead signals. Integr Med Res 2018; 7(2):109-25. doi: 10.1016/j.imr.2018.03.005 [Crossref]
132. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 2020; 5(4):562-9. doi: 10.1038/s41564-020-0688-y [Crossref]
133. Ratia K, Saikatendu KS, Santarsiero BD, Barretto N, Baker SC, Stevens RC. Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme. Proc Natl Acad Sci U S A 2006; 103(15):5717-22. doi: 10.1073/pnas.0510851103 [Crossref]
134. Remali J, Aizat WM. A review on plant bioactive compounds and their modes of action against coronavirus infection. Front Pharmacol 2020; 11:589044. doi: 10.3389/fphar.2020.589044 [Crossref]
135. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG. A new coronavirus associated with human respiratory disease in China. Nature 2020; 579(7798):265-9. doi: 10.1038/s41586-020-2008-3 [Crossref]
136. Li F. Structure, function, and evolution of coronavirus spike proteins. Annu Rev Virol 2016; 3(1):237-61. doi: 10.1146/annurev-virology-110615-042301 [Crossref]
137. Zhu RF, Gao YL, Robert SH, Gao JP, Yang SG, Zhu CT. Systematic review of the registered clinical trials for coronavirus disease 2019 (COVID-19). J Transl Med 2020; 18(1):274. doi: 10.1186/s12967-020-02442-5 [Crossref]