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Dietary therapy and herbal medicine for COVID-19 prevention: A review and
perspective

Suraphan Panyod, Chi-Tang Ho, Lee-Yan Sheen

PII: S2225-4110(20)30506-X
DOI: https://doi.org/10.1016/j.jtcme.2020.05.004
Reference: JTCME 407

To appear in: Journal of Traditional and Complementary Medicine

Received Date: 27 April 2020

Revised Date: 29 May 2020
Accepted Date: 29 May 2020

Please cite this article as: Panyod S, Ho CT, Sheen LY, Dietary therapy and herbal medicine for
COVID-19 prevention: A review and perspective, Journal of Traditional and Complementary Medicine
(2020), doi: https://doi.org/10.1016/j.jtcme.2020.05.004.

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Fig. X| Perspective of Herbal medicine for COVID-19 prevention

COVID-19

? ?
? ?

Using foods and herbs as Use as an anti-viral agent Use as an air-disinfectant Use as a surface sanitizing
diet or supplement to by coating on masks (essential oil) to stop agent to provide a
prevent infection and aerosol transmission disinfected environment
strengthen immunity

Herbal medicine and its bioactive compound

 1 Dietary Therapy and Herbal Medicine for COVID-19 Prevention: A
2 Review and Perspective
3
4 Suraphan Panyoda, Chi-Tang Hob, *, Lee-Yan Sheena, c, d, *
5
a
6 Institute of Food Science and Technology, National Taiwan University, Taipei,
7 Taiwan.
b
8 Department of Food Science, Rutgers University, New Brunswick, New Jersey,
9 United States.
c
10 Center for Food and Biomolecules, National Taiwan University, Taipei, Taiwan.
d
11 National Center for Food Safety Education and Research, National Taiwan
12 University, Taipei, Taiwan.
13
14 *Corresponding author:
15 Lee-Yan Sheen. Institute of Food Science and Technology, National Taiwan
16 University
17 No. 1, Section 4, Roosevelt Road, Taipei 106, Taiwan 

18 Tel: 886-2-33664129; Fax: 886-2-23620849; E-mail: lysheen@ntu.edu.tw
19
20 Chi-Tang Ho. Food Science Department, Rutgers University
21 65 Dudley Road, New Brunswick, NJ 08901-8520, USA
22 Tel: (848) 932-5553; Fax: (732) 932-6776; Email: ho@aesop.rutgers.edu
23

1
24 ABSTRACT
25
26 A novel coronavirus disease (COVID-19), transmitted from humans to
27 humans, has rapidly become the pandemic responsible for the current global health
28 crisis. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2
29 (SARS-CoV-2), which is said to be of zoonotic origin. This review describes the
30 etiology and signs and symptoms as well as the current allopathic therapy for
31 COVID-19. Additionally, findings of previous studies on the immunomodulatory
32 effects and antiviral activities of particular foods and herbs on influenza virus and
33 coronaviruses have been collated, with the aim of promoting the use of dietary
34 therapy and herbal medicine as COVID-19 preventive therapies, while specific drugs
35 and vaccines are yet to be discovered or are still under development. The volume of
36 existing reports is irrefutable evidence that foods and herbs possess a potential
37 antiviral ability against SARS-CoV-2 and can prevent COVID-19. Foods and herbs
38 could be used as dietary or complementary therapy to prevent infection and strengthen
39 immunity, as antiviral agents for masks, as disinfectants to curb aerosol transmission,
40 or as sanitizing agents to disinfect surfaces. However, these hypotheses need to be
41 experimentally verified for SARS-CoV-2 and COVID-19 patients.
42
43 Keywords: COVID-19, SARS-CoV-2, coronavirus, dietary therapy, herbal medicine,
44 herbs, prevention
45

2
46 1. Introduction
47 At the end of December 2019, the coronavirus outbreak caused by severe
48 acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei,
1
49 China, leading to the rapid spread of 2019 novel coronavirus (COVID-19) into a
2,3
50 pandemic responsible for the current global health crisis. In May 2020, there have
51 been approximately 5 million confirmed cases of COVID-19 and more than 30
4
52 thousand deaths worldwide, as reported by the WHO. In this review, we aim to
53 report historical records on the antiviral activity of a particular diet and herbal
54 medicine on influenza virus, SARS-CoV-1, and SARS-CoV-2. This will promote the
55 use of dietary therapy and herbal medicine as complementary COVID-19 prevention
56 therapies, given the current absence of an effective drug and/or vaccine against
57 COVID-19/SARS-COV-2. Several doctors and researchers have already attempted to
5
58 use herbal medicines on clinical trials against SARS-CoV-2. The longstanding use
59 of dietary therapy and herbal medicine to prevent and treat diseases cannot be
6
60 overemphasized, as several herbs exhibit antiviral activity. Using dietary therapy
61 and herbal medicine to prevent SARS-CoV-2 infections could be a complementary
62 COVID-19 therapy, while drugs remain under development.
63
64 2. Methods
65 In this review and perspective, the authors searched and collected data related
66 to COVID-19, herbal medicine, and dietary therapy. Google Scholar, PubMed,
67 SciFinder, and ScienceDirect were the main search engines used. The search terms
68 used included: coronavirus; etiology; signs; symptoms; allopathic therapy against
69 COVID-19; immunomodulatory and antiviral activities of herbs against influenza,
70 SARS-CoV-1, and SARS-CoV-2. The chosen articles were reviewed and interpreted
71 by the authors. The perspective is an opinion of the authors regarding the use of foods
72 and herbs as a prevention and complementary therapy against COVID-19.
73
74 3. Results and discussion
75 3.1. Etiology, Signs, and Symptoms of COVID-19
76 Early discoveries of COVID-19 pneumonia patients were suspected to be
77 associated with the Huanan seafood market in Wuhan, where wild-animal trading
78 occurred. 7 SARS-CoV-2 is postulated to have originated from a bat, because its full-
79 length genomes are similar to the bat-derived SARS-CoV genome: 88% identical
3
 80 (Figure 1). Phylogenetic analyses indicate that SARS-CoV-2 belongs to the subgenus
81 Sarbecovirus of the genus Betacoronavirus. More so, homology modeling studies
82 reveal that the receptor-binding domain structure of SARS-CoV-1 is similar to that of
8
83 SARS-CoV-2. SARS-CoV-2 might amplify in the intermediate mammalian host,
84 probably pangolin, since the whole-genome of pangolin-CoV is 91.02% identical to
9
85 SARS-CoV-2. In a previous study, molecular and phylogenetic data showed that
10
86 SARS-CoV-2 did not emerge directly from the pangolin-CoV. However, the origin
87 of the transmission from pangolin-to-human is still in debate. Trading pangolin in wet
88 markets should therefore be strictly prohibited to reduce the risk of future zoonotic
11
89 transmission. SARS-CoV-2 genomes have now mutated into 3 types; A, B, and C.
90 Type A is closest to the ancestral bat-derived coronavirus. Great proportions of types
91 A and C have been observed in Europeans and Americans, while type B is mainly
92 found in East Asia. 12
93 SARS-CoV-2 is a human-to-human aerosol transmission, 13 making the fear of
94 contracting COVID-19 a major panic-trigger amongst numerous individuals. Based
95 on data collected from 99 COVID-19 patients admitted in Jinyintan Hospital, Wuhan,
96 the typical signs and symptoms include fever (83%), cough (82%), and shortness of
97 breath (31%), which are often accompanied by muscle ache (10%), confusion (9%),
14
98 headache (8%), and sore throat (5%) (Figure 2). Approximately 75% of these
99 patients also presented with bilateral pneumonia (75%), 17% of them had acute
100 respiratory distress syndrome, and 11% died over a short time span, owing to multi-
101 organ failure. 14 Another study observed that the time from illness onset to dyspnea is
102 approximately 8 days. In this study, 63% of patients had lymphopenia, and all the
15
103 patients presented with pneumonia. Other reliable indicators include the loss of
104 taste and smell. 16
105
106 3.2. Allopathic Therapy against COVID-19
107 During the SARS-CoV-2 spread in Wuhan, allopathic therapy was used for
108 COVID-19 treatment in the Wuhan Jinyintan Hospital (based on 99 patients),
109 including antiviral treatment (76%), antibiotic treatment (71%), oxygen therapy
14
110 (75%), and intravenous immunoglobulin therapy (27%), although no COVID-19
111 drug has been approved by the US Food and Drug Administration. There is also no
17
112 effective pharmacologic treatment against COVID-19. Determining the drug target
113 requires an understanding of the viral lifecycle. SARS-CoV-2 is a single-stranded
4
 18
114 RNA-enveloped virus. SARS-CoV-2 and SARS-CoV-1 share similar host-entry
115 mechanisms. It targets the cells by using the viral structural spike (S) protein bind
116 with angiotensin-converting enzymes 2 (ACE2) receptor forming endosomes which
117 enter the cells. TMPRSS2 is a host type 2 transmembrane serine protease helping
118 virus enter through S protein. After the virus enters the cell, it synthesizes viral
119 polyprotein, and RNA subsequently assembles and releases the new virus particles.
120 Inhibiting viral cell entry and replication and modulating the immune system could be
19
121 a potential target for drug therapy. Current clinical tries on COVID-19
122 pharmacological treatments include hydroxychloroquine and remdesivir.
123 Hydroxychloroquine, which reduces the viral load in COVID-19 patients, appears to
124 be more effective when used in combination with azithromycin. 20 Remdesivir proved
21
125 its potential against COVID-19 by displaying clinical improvement. While many
126 clinical trials aimed at discovering a potential effective COVID-19 drug are ongoing,
127 using herbal medicines with well-known antiviral activity might be a complementary
128 SARS-CoV-2 preventive therapy.
129
130 3.3. Immunomodulatory Effect of Foods and Herbs and their Antiviral
131 Activities against Influenza, SARS-CoV-1, and SARS-CoV-2
132 Coronavirus can be treated using nutrition; for instance, treating influenza
133 with very large amounts of vitamin C has been practiced for decades. The common
134 cold, SARS-CoV-1, and SARS-CoV-2 fall under the same coronavirus family; hence,
22
135 are regarded as the same viral type. Therefore, vitamin C may be effective against
136 COVID-19; clinical studies are required. An evidence showed that vitamin D
137 decreased the risk of COVID-19 outbreak in winter, which is a time when 25-
138 hydroxyvitamin D (25(OH)D) level is low. Thus, vitamin D intake may reduce the
23
139 risk of influenza and COVID-19 infections and related deaths. Many foods and
140 herbs are known to display antiviral and immunomodulatory activities. Aloe vera,
141 Angelica gigas (Korean angelica), Astragalus membranaceus (Mongolian milkvetch),
142 Ganoderma lucidum (lingzhi mushroom), Panax ginseng (ginseng), and Scutellaria
143 baicalensis (Chinese skullcap) have been reported to exhibit immunomodulatory
144 properties. 24 Their activities are based on selectively stimulating cytokines, activating
145 lymphocytes, increasing natural killer cell counts, and enhancing macrophage actions.
146 Rice bran, wheat bran, Lawsonia alba (hina), Echinacea purpurea (eastern purple
147 coneflower), Plumbago zeylanica (Ceylon leadwort), and Cissampelos pareira Linn
5
148 (velvetleaf) also exhibit immunomodulatory properties by stimulating phagocytosis.
149 Eucalyptus essential oil is reported to improve the innate cell-mediated immune
150 response that can be used as an immunoregulatory agent against infectious diseases.
25,26
151 Collectively, using these immunomodulatory foods and herbs could enhance the
152 immune system and protect the body against COVID-19. However, these observations
153 must be verified through scientific or clinical studies.
154 Numerous studies, although limited to in vitro, in vivo, and in ovo studies,
155 have reported the bioactive components of foods and herbs against the influenza virus
156 and SAR-CoV-1. Only a few clinical studies have been carried on the effects of
157 specific foods and herbs against the influenza virus and SAR-CoV-1, as most clinical
158 studies have been done on food and herb combinations, or the traditional Chinese
159 formulas. 27 The antiviral activities reported for foods and herbs against the influenza
160 virus are shown in Table 1. The antiviral influenza study models have mainly been
161 Madin-Darby Canine Kidney cells (MDCK) and murine models, with the influenza
162 strains being the influenza A virus subtype H1N1, H9N2, and H11N9. The extracts or
163 bioactive compounds of garlic, ginger, Korean red ginseng, eucalyptus, tea tree,
164 Tianmingjing, Machixian, fish mint, Chinese mahogany, cape jasmine, zhebeimu
165 have been shown to exhibit antiviral activity against the influenza virus. 28-39
166 The mode of action for influenza virus A inhibition is via inhibition of
167 proliferation or penetration into MDCK cells. Garlic and ginger were found to
28,29
168 inactivate avian influenza virus H9N2 activity in both chick embryos. The
169 ethanolic extract and polysaccharides of fish mint have been shown to alleviate
170 H1N1-induced acute lung injury in mice, hence simultaneously improving the
171 immune system. 35
The aqueous extract of zhebeimu can inhibit H1N1 replication in
39
172 embryonated eggs and increase the survival rate of virus-infected mice. Some
173 essential oils have been shown to exhibit anti-influenza activities. These include
174 Cinnamomum zeylanicum leaf oil (cinnamon), Citrus bergamia (bergamot),
40
175 Cymbopogon flexuosus (lemongrass) and Thymus vulgaris (Red Thyme). A blend
176 of essential oils also inhibits the infectivity of influenza virus via inactivating viral
41
177 binding ability and viral protein translation in MDCK cells. Tea tree oil and
178 eucalyptus oil capturing on the fiber coating materials are capable of inactivating
179 influenza virus A. 32
180 Chinese mahogany, Chinese liquorice, red spider lily, the rhizome of Scythian
181 lamb, and its extract or compound, have reported anti-SARS-CoV-1 activity in Vero
6
 42-45
182 cells with the SARS-CoV-1 infection model (Table 2). Although some natural
46
183 products as baicalein and baicalin were proved as the inhibitors of SARS-CoV-2,
184 there has been no published study on a single herb, its extract, and bioactive
185 compound against SARS-CoV-2. Ding et al. (2017) investigated Lianhuaqingwen, a
186 Traditional Chinese Medicine formula composed of a combination of 13 herbs (Table
47
187 3). Lianhuaqingwen suppressed SARS-CoV-2 replication, reduced pro-
188 inflammatory cytokine production, and changed the morphology of SARS-CoV-2
189 cells. 48 SARS-CoV-2 can cause dangerous and potentially lethal diseases through the
190 respiratory route. Hence, studying the effect of a particular bioactive compound
191 against SAR-CoV-2 requires a highly contained laboratory with inward directional
192 airflow (Biosafety level 3; BSL-3), 49 posing a challenges for most researchers.
193
194 3.4. Perspective for Using Foods and Herbs against COVID-19
195 Current literature carries strong evidence in support of dietary therapy and
196 herbal medicine as potential effective antivirals against SARS-CoV-2 and preventive
197 agents against COVID-19. For future studies, the authors believe there are 4 potential
198 approaches for the application of dietary therapy and herbal medicine against
199 COVID-19: (1) using foods and herbs as diet or supplement to prevent infection and
200 strengthen immunity; (2) use as an antiviral agent by coating on masks; (3) use as an
201 air-disinfectant (essential oil) to stop aerosol transmission; and (4) use as a surface
202 sanitizing agent to provide a disinfected environment (Figure 3).
203 Surgical masks are good at preventing virus spread into the air and
50,51
204 transmission to humans. However, after mask removal, the virus remains on the
205 mask and is probably re-aerosolized, increasing the risk of human infection. Mask
206 coating with an antiviral compound could be advantageous, but disinfectant toxicity to
207 humans must be considered.
208 Aromatherapy has been used for thousands of years in Egypt and India to treat
52
209 various diseases, and the antimicrobial and antiviral activity of essential oils have
53
210 been confirmed by numerous studies. However, most of these studies only
211 investigated the effect of their liquid formula, limiting their administration to only via
212 the oral route. Using essential oils vapors could increase their application against
213 airborne bacteria and viruses. The anti-influenza virus activity of some essential oil
214 vapors, such as that of Citrus bergamia (bergamot), Eucalyptus globulus (eucalyptus),
215 Pelargonium graveolens (geranium), Cinnamomum zeylanicum leaf oil (cinnamon),
7
216 and Cymbopogon flexuosus (lemongrass), has been reported. Their inhibitory
217 mechanism is based on the inactivation of the principal external proteins of the
218 influenza virus. The hemagglutinin protein of the virus appeared to be a major target
219 of most of these oil vapors, and this may provide therapeutic benefits for people
40
220 suffering from influenza or other respiratory viral infections. Aerosolized tea tree
221 oil reportedly inhibits airborne viral particles of H11N9 subtype avian influenza virus.
32
222 There are currently very few studies on the potential of the vapor form of essential
223 oils. Air sterilization without human health damage using essential oils could be a
224 good way to prevent COVID-19. However, the minimum essential oil concentration
225 needed for SARS-CoV-2 inhibition should be investigated.
226 Many restaurants use cleaning detergents for surface sanitization; however,
227 their safety and disinfection efficiency need further consideration. Natural antiviral
228 extracts from herbs could be added to cleaning detergents to increase their anti-SARS-
229 CoV-2 activity.
230
231 4. Conclusions
232 Currently, there are limited number of allopathic medicines considered
233 effective against COVID-19. The design and development of drugs and vaccines
234 require elucidation of the mechanism of SARS-CoV-2. Current literature provides
235 obvious evidence supporting dietary therapy and herbal medicine as potential
236 effective antivirals against SARS-CoV-2 and as preventive agents against COVID-19.
237 Thus, dietary therapy and herbal medicine could be a complementary preventive
238 therapy for COVID-19. However, these hypotheses require experimental validation in
239 SARS-Cov-2 infection models and COVID-19 patients.

8
240 Figure legends
241
242 Figure 1. SARS-CoV-2 etiology, transmission cycle, and structure. SARS-CoV-2
243 reportedly originates from bats, zoonotically transmitted to the intermediate
244 mammalian host pangolin, 8,9 however, its origin is still under debating. SARS-CoV-2
245 belongs to the subgenus Sarbecovirus of the genus Betacoronavirus. Its genome
12
246 mutates to form 3 types: A, B, and C. It is an airborne disease transmitted from
247 human-to-human. COVID-19 is currently a pandemic and global health crisis. 2
248
249 Figure 2. Data from 99 patients admitted at Jinyintan Hospital, Wuhan, suggest the
250 principal signs and symptoms of COVID-19 include fever, cough, shortness of breath,
14
251 muscle ache, confusion, headache, and sore throat. Loss of taste and smell is
252 another strong indicator of SARS-CoV-2 infection. 16
253
254 Figure 3. The prospects of dietary therapy and herbal medicine for COVID-19
255 prevention. Dietary therapy and herbal medicine could be used against COVID-19 in
256 the following four ways: (1) diet or supplement for infection prevention and immunity
257 strengthening; (2) application as antiviral agent on masks; (3) air disinfection agent to
258 stop aerosol transmission of the virus; and (4) surface sanitizing agent to afford a
259 disinfected environment.

9
260 Figures
261

262
263 Figure 1
264

10
265
266 Figure 2
267

11
268
269 Figure 3
270

12
271 Tables
272 Table 1. Antiviral activity of foods and herbs against influenza virus
273
Bioactive compound and
Herbs Experimental model Mode of action References
extract

Allium sativum Rasool et al.

H9N2 virus infection in MDCK cells Anti-avian influenza virus H9N2 activity in
Garlic aqueous extract (2017) 28
(Garlic; 大蒜; Dà suàn) and chicken embryo both chick embryos and cell models

Inhibits H1N1 virus penetration and

Mehrbod et al.
Garlic extract H1N1 virus infection in MDCK cells proliferation in cell culture
(2008) 29

Zingiber officinalis Rasool et al.

H9N2 virus infection in MDCK cells Anti-avian influenza virus H9N2 activity in
Ginger aqueous extract (2017) 28
(Ginger; 薑; Jiāng) and chicken embryo both chick embryos and cell models

Ginseng enhances immunity by increasing

Panax ginseng C.A. the levels of influenza A virus-specific
Meyer Korean red ginseng antibodies and their neutralizing activities.
H1N1 virus-induced respiratory tract Quan et al.
(Korean red ginseng; powder capsule It modulates CD69-expressing immune cells
infection in mice and MDCK cells (2006) 30
and exhibits significant enhancement of
紅參; Hóng cān)
influenza virus-specific IgA antibody in
mice lungs.
Eucalyptus polybractea Aerosol and vapor of
Inhibits avian influenza virus H11N9 in Usachev et al.
(Eucalyptus; 桉樹; Ān eucalyptus oil H11N9 virus infection in MDCK cells
aerosol and vapor form
31
(2013)
shù)

Pre-coated eucalyptus oil inactivates Pyankov et al.

Eucalyptus oil H11N9 virus infection in MDCK cells
captured H11N9 virus in fiber material (2012) 32

Melaleuca alternifolia
Aerosol and vapor of tea Inhibits avian influenza virus H11N9 in Usachev et al.
(Tea tree; 茶樹; Chá H11N9 virus infection in MDCK cells
tree oil aerosol and vapor form (2013) 31
shù)

Pre-coated tea tree oil inactivates captured Pyankov et al.

Tea tree oil H11N9 virus infection in MDCK cells
H11N9 fiber material (2012) 32

Carpesium
4α,5α-dihydroxy-guaia-
abrotanoides L. He et al. (2020)
11(13)-en- 12,8α- H11N9 virus infection in MDCK cells Inhibits H1N1 virus activity 33
(Tianmingjing; 天名精;
lactone
Tiān míng jīng)

Portulaca oleracea L. Inhibits H1N1 and H3N2 in the early stages

Water extract of P. of influenza A virus infection, inhibits the Li et al. (2019)
(Machixian; 馬齒莧; H11N9 virus infection in MDCK cells 34
oleracea L. binding of virus to cells, and exhibits good
Mǎ chǐ xiàn) virucidal activity.
Alleviates H1N1-induced acute lung injury
Houttuynia cordata in mice through antiviral and anti-
H. cordata ethanolic H1N1 virus-induced acute lung injury Ling et al.
(Fish mint; 魚腥草; Yú inflammatory effects. Inhibition of viral
extract in mice and RAW 264.7 cell model (2020) 35
xīng cǎo) neuraminidase activity and toll like receptor
signaling
H. cordata H1N1 virus-induced acute lung injury Alleviates lung injury and intestinal Chen et al.
polysaccharide mouse model dysfunction (2019) 36
Toona sinensis
Inhibits H1N1 mRNA replication and
(Chinese mahogany; 香 Catechin and gallic acid H1N1 virus infection in MDCK cells MDCK plaque formation, neuraminidase
You et al.
(2018) 37
椿; Xiāng chūn) activity, and viral glycoprotein

Gardenia jasminoides Protects MDCK from H1N1 virus-induced

Ellis cell injury and inhibits virus-induced
H1N1 virus-induced respiratory tract Zhang et al.
Geniposide alveolar wall changes, alveolar hemorrhage,
(Cape jasmine; 梔子; infection in mice and MDCK cells (2017) 38
neutrophil-infiltration, and inflammation in
Zhī zi) mice lungs
Fritillaria thunbergii Inhibits H1N1 replication in embryonated
F. thunbergii aqueous H1N1 virus-induced respiratory tract
(Zhebeimu; 浙貝母; eggs. Protects MDCK cells from H1N1 Kim et al.
extract infection in mice, virus infection in
Zhè bèi mǔ) virus-induced cell injury. Increases mice (2020) 39
MDCK cells and in ovo studies
survival rate from viral infection.

274
275
13
276 Table 2. Antiviral activity of foods and herbs against severe acute respiratory
277 syndrome coronavirus 1 (SARS-CoV-1)
278
Bioactive compound and
Herbs Experimental model Mode of action References
extract
Toona sinensis Roem
Tender leaf of Toona Vero cell with SARS-CoV-1 strain
(Chinese mahogany; 香 Chen et al.
sinensis Roem crude FFM 1 infection model Inhibits SARS-CoV-1 replication
(2008) 42
椿; Xiāng chūn) extract fraction

Glycyrrhiza radix
Hoever et
(Chinese liquorice; 甘 Glycyrrhizic Acid Vero cell with SARS-CoV-1 strain Inhibits SARS-CoV-1 and increase
al. (2005)
Derivatives FFM 1 infection model cytotoxicity 43
草; Gān cǎo)

Lycoris radiata
Vero cell with SARS-CoV-1 strain Li et al.
(Red spider lily; 石蒜; Lycorine
BJ001 and BJ006 infection model
Inhibits SARS-CoV-1 replication
(2005) 44
Shí suàn)

Rhizoma Cibotii
(Rhizome of Scythian Vero cell with SARS-CoV-1 Wen et al.
Rhizoma Cibotii extract Inhibits SARS-CoV-1 replication
infection model (2011) 45
Lamb; 狗脊; gǒujǐ)

279
280

14
281 Table 3. Antiviral activity of herbs against severe acute respiratory syndrome
282 coronavirus 2 (SARS-CoV-2)
283
Herbs Bioactive compound and extract Experimental model Mode of action References

Lianhua-Qingwen formula (13 herbs) (Ding et al. ,2017)

• Forsythia suspensa (Thunb.) Vahl (Weeping
forsythia; 連翹; Lián qiáo)
• Ephedra sinica Stapf (Chinese ephedra; 草麻黃;
Cǎo má huáng)
• Lonicera japonica Thunb. (Japanese honeysuckle;
忍冬; Rěndōng)
• Isatis indigotica Fortune (Woad; 菘藍; Sōng lán)
• Mentha haplocalyx Briq. (Mint; 薄荷; Bò hé)
• Dryopteris crassirhizoma Nakai (Thick-stemmed Inactivate SARS-CoV-2
wood fern; 粗莖鱗毛蕨; Cū jīng lín máo jué) replication, reduced pro-
Lianhuaqingwen
• Rhodiola rosea L. (Golden root, ;紅景天; Hóng Vero E6 cells with SARS- inflammatory cytokines Li et al.
(連花清瘟; Lián jǐng tiān) CoV-2 infection model production and affect (2020) 48
huā qīng wēn) • Gypsum Fibrosum (Gypsum; 石膏; Shí gāo) particle morphology of
• Pogostemon cablin (Blanco) Benth. (Patchouli; 廣 virus cell.
藿香; Guǎng huò xiāng)
• Rheum palmatum L. (Chinese rhubarb; 掌葉大黃;
Zhǎng yè dà huáng)
• Houttuynia cordata Thunb. (魚腥草; Yú xīng cǎo;
Fish mint)
• Glycyrrhiza uralensis Fisch. (Chinese liquorice;
甘草; Gāncǎo)
• Armeniaca sibirica (L.) Lam. (Siberian apricot; 山
杏; Shān xìng)47

284
285

15
286 References
287 1. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of
288 global health concern. Lancet. 2020;395(10223):470-473.
289 2. Bedford J, Enria D, Giesecke J, Heymann DL, Ihekweazu C, Kobinger G,
290 Lane HC, Memish Z, Oh MD, Sall AA, Schuchat A, Ungchusak K, Wieler LH.
291 for the WHO Strategic and Technical Advisory Group for Infectious Hazards.
292 COVID-19: Towards controlling of a pandemic. Lancet.
293 2020;395(10229):1015-1018.
294 3. Di Gennaro F, Pizzol D, Marotta C, Antunes M, Racalbuto V, Veronese N,
295 Smith L. Coronavirus diseases (COVID-19) current status and future
296 perspectives: a narrative review. Int J Environ Res Public Health. 2020;17(8).
297 4. WHO. Coronavirus disease (covid-19) pandemic. 2020;17(8):2690.
298 https://www.who.int/emergencies/diseases/novel-coronavirus-
299 2019?gclid=cj0kcqjwzzj2brdvarisabs3l9l2f-qlqqz-
300 ni5zltz8ytn8uvinukfefr_jrf3l1bastxo8zlddogyaai9realw_wcb.
301 5. Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese medicine in
302 the treatment of patients infected with 2019-New Coronavirus (SARS-CoV-2):
303 A review and perspective. Int J Biol Sci. 2020;16(10):1708-1717.
304 6. Huang J, Su D, Feng Y, Liu K, Song Y. Antiviral herbs-present and future.
305 Infect Disord Drug Targets. 2014;14(1):61-73.
306 7. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, Hu Y, Tao ZW, Tian JH,
307 Pei YY, Yuan ML, Zhang YL, Dai FH, Liu Y, Wang QM, Zheng JJ, Xu L,
308 Holmes EC, Zhang YZ. A new coronavirus associated with human respiratory
309 disease in China. Nature. 2020;579(7798):265-269.
310 8. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu
311 N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L,
312 Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu
313 W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic
314 characterisation and epidemiology of 2019 novel coronavirus: Implications for
315 virus origins and receptor binding. Lancet. 2020;395(10224):565-574.
316 9. Zhang T, Wu Q, Zhang Z. Probable pangolin origin of SARS-CoV-2
317 associated with the COVID-19 outbreak. Curr Biol. 2020;30(7):1346-1351
318 e1342.

16
319 10. Liu P, Jiang JZ, Wan XF, Hua Y, Li L, Zhou J, Wang X, Hou F, Chen J, Zou J,
320 Chen J. Are pangolins the intermediate host of the 2019 novel coronavirus
321 (SARS-CoV-2)? PLoS Pathog. 2020;16(5):e1008421.
322 11. Lam TT, Shum MH, Zhu HC, Tong YG, Ni XB, Liao YS, Wei W, Cheung
323 WY, Li WJ, Li LF, Leung GM, Holmes EC, Hu YL, Guan Y. Identifying
324 SARS-CoV-2 related coronaviruses in Malayan pangolins. Nature. 2020:
325 doi:10.1038/s41586-020-2169-0.
326 12. Forster P, Forster L, Renfrew C, Forster M. Phylogenetic network analysis of
327 SARS-CoV-2 genomes. Proc Natl Acad Sci USA. 2020;117(17):9241-9243.
328 13. Liu Y, Ning Z, Chen Y, Guo M, Liu Y, Gali NK, Sun L, Duan Y, Cai J,
329 Westerdahl D, Liu X, Ho K-f, Kan H, Fu Q, Lan K. Aerodynamic
330 characteristics and rna concentration of SARS-CoV-2 aerosol in wuhan
331 hospitals during COVID-19 outbreak. BioRxiv. 2020:2020.2003.2008.982637.
332 14. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei
333 Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical
334 characteristics of 99 cases of 2019 Novel Coronavirus pneumonia in Wuhan,
335 China: A descriptive study. Lancet. 2020;395(10223):507-513.
336 15. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X,
337 Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y,
338 Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B.
339 Clinical features of patients infected with 2019 Novel Coronavirus in Wuhan,
340 China. Lancet. 2020;395(10223):497-506.
341 16. Menni C, Valdes A, Freydin MB, Ganesh S, El-Sayed Moustafa J, Visconti A,
342 Hysi P, Bowyer RCE, Mangino M, Falchi M, Wolf J, Steves C, Spector T.
343 Loss of smell and taste in combination with other symptoms is a strong
344 predictor of COVID-19 infection. MedRxiv. 2020:2020.2004.2005.20048421.
345 17. CDC. Information for clinicians on investigational therapeutics for patients
346 with COVID-19. 2020; https://www.cdc.gov/coronavirus/2019-
347 ncov/hcp/therapeutic-options.html.
348 18. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S,
349 Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C,
350 Pohlmann S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is
351 blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280
352 e278.
17
353 19. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic
354 treatments for coronavirus disease 2019 (COVID-19): A review. JAMA.
355 2020;323(18):1824-1836.
356 20. Gautret P, Lagier J-C, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B,
357 Courjon J, Giordanengo V, Vieira VE, Dupont HT, Honoré S, Colson P,
358 Chabrière E, La Scola B, Rolain J-M, Brouqui P, Raoult D.
359 Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results
360 of an open-label non-randomized clinical trial. Internat J Antimicrobial Agents.
361 2020:105949.
362 21. Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, Feldt T,
363 Green G, Green ML, Lescure F-X, Nicastri E, Oda R, Yo K, Quiros-Roldan E,
364 Studemeister A, Redinski J, Ahmed S, Bernett J, Chelliah D, Chen D, Chihara
365 S, Cohen SH, Cunningham J, D’Arminio Monforte A, Ismail S, Kato H,
366 Lapadula G, L’Her E, Maeno T, Majumder S, Massari M, Mora-Rillo M,
367 Mutoh Y, Nguyen D, Verweij E, Zoufaly A, Osinusi AO, DeZure A, Zhao Y,
368 Zhong L, Chokkalingam A, Elboudwarej E, Telep L, Timbs L, Henne I,
369 Sellers S, Cao H, Tan SK, Winterbourne L, Desai P, Mera R, Gaggar A,
370 Myers RP, Brainard DM, Childs R, Flanigan T. Compassionate use of
371 remdesivir for patients with severe COVID-19. NEJM. 2020, doi:
372 10.1056/nejmoa2007016.
373 22. Saul AW. Nutritional treatment of coronavirus. Orthomolecular Med News
374 Ser. 2020.
375 23. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL,
376 Bhattoa HP. Evidence that vitamin d supplementation could reduce risk of
377 influenza and COVID-19 infections and deaths. Nutrients. 2020;12(4):988.
378 24. Tan BKH, Vanitha J. Immunomodulatory and antimicrobial effects of some
379 traditional chinese medicinal herbs: A review. Curr Med Chem.
380 2004;11(11):1423-1430.
381 25. Serafino A, Vallebona PS, Andreola F, Zonfrillo M, Mercuri L, Federici M,
382 Rasi G, Garaci E, Pierimarchi P. Stimulatory effect of eucalyptus essential oil
383 on innate cell-mediated immune response. Bmc Immunol. 2008;9:17.
384 26. Sadlon AE, Lamson DW. Immune-modifying and antimicrobial effects of
385 eucalyptus oil and simple inhalation devices. Altern Med Rev. 2010;15(1):33-
386 42.
18
387 27. Luo H, Tang QL, Shang YX, Liang SB, Yang M, Robinson N, Liu JP. Can
388 Chinese medicine be used for prevention of Corona Virus Disease 2019
389 (COVID-19)? a review of historical classics, research evidence and current
390 prevention programs. Chin J Integr Med. 2020;26(4):243-250.
391 28. Rasool A, Khan MU, Ali MA, Anjum AA, Ahmed I, Aslam A, Mustafa G,
392 Masood S, Ali MA, Nawaz M. Anti-avian influenza virus H9N2 activity of
393 aqueous extracts of Zingiber officinalis (ginger) and allium sativum (garlic) in
394 chick embryos. Pak J Pharm Sci. 2017;30(4):1341-1344.
395 29. Mehrbod P, Amini E, Tavassoti-Kheiri M. Antiviral activity of garlic extract
396 on influenza virus. Iranian Journal of Virology. 2009;3(1):19-23.
397 30. Quan FS, Compans RW, Cho YK, Kang SM. Ginseng and salviae herbs play a
398 role as immune activators and modulate immune responses during influenza
399 virus infection. Vaccine. 2007;25(2):272-282.
400 31. Usachev EV, Pyankov OV, Usacheva OV, Agranovski IE. Antiviral activity of
401 tea tree and eucalyptus oil aerosol and vapour. J Aerosol Sci. 2013;59:22-30.
402 32. Pyankov OV, Usachev EV, Pyankova O, Agranovski IE. Inactivation of
403 airborne influenza virus by tea tree and eucalyptus oils. Aerosol Sci Tech.
404 2012;46(12):1295-1302.
405 33. He YQ, Cai L, Qian QG, Yang SH, Chen DL, Zhao BQ, Zhong ZP, Zhou XJ.
406 Anti-influenza a (H1N1) viral and cytotoxic sesquiterpenes from carpesium
407 abrotanoides. Phytochem Lett. 2020;35:41-45.
408 34. Li YH, Lai CY, Su MC, Cheng JC, Chang YS. Antiviral activity of Portulaca
409 oleracea L. against influenza a viruses. J Ethnopharmacol. 2019;241:112013.
410 35. Ling LJ, Lu Y, Zhang YY, Zhu HY, Tu P, Li H, Chen DF. Flavonoids from
411 Houttuynia cordata attenuate H1N1-induced acute lung injury in mice via
412 inhibition of influenza virus and toll-like receptor signalling. Phytomed.
413 2020;67:153150.
414 36. Chen MY, Li H, Lu XX, Ling LJ, Weng HB, Sun W, Chen DF, Zhang YY.
415 Houttuynia cordata polysaccharide alleviated intestinal injury and modulated
416 intestinal microbiota in h1n1 virus infected. Chin J Nat Med. 2019;17(3):187-
417 197.
418 37. You HL, Huang CC, Chen CJ, Chang CC, Liao PL, Huang ST. Anti-pandemic
419 influenza a (H1N1) virus potential of catechin and gallic acid. J Chin Med
420 Assoc. 2018;81(5):458-468.
19
421 38. Zhang YS, Yao J, Qi X, Liu X, Lu XQ, Feng GZ. Geniposide demonstrates
422 anti-inflammatory and antiviral activity against pandemic A/Jiangsu/1/2009
423 (H1N1) influenza virus infection in vitro and in vivo. Antivir Ther.
424 2017;22(7):599-611.
425 39. Kim M, Nguyen DV, Heo Y, Park KH, Paik HD, Kim YB. Antiviral activity
426 of fritillaria thunbergii extract against human influenza virus H1N1 (PR8) in
427 vitro, in ovo and in vivo. J Microbiol Biotechn. 2020;30(2):172-177.
428 40. Vimalanathan S, Hudson J. Anti-influenza virus activity of essential oils and
429 vapors. Amer J Essential Oil Nat Prod. 2014;2(1):47-53.
430 41. Wu SH, Patel KB, Booth LJ, Metcalf JP, Lin HK, Wu WX. Protective
431 essential oil attenuates influenza virus infection: an in vitro study in mdck
432 cells. Bmc Complem Altern Med. 2010;10:69.
433 42. Chen CJ, Michaelis M, Hsu HK, Tsai CC, Yang KD, Wu YC, Cinatl J, Jr.,
434 Doerr HW. Toona sinensis roem tender leaf extract inhibits SARS coronavirus
435 replication. J Ethnopharmacol. 2008;120(1):108-111.
436 43. Hoever G, Baltina L, Michaelis M, Kondratenko R, Baltina L, Tolstikov GA,
437 Doerr HW, Cinatl J, Jr. Antiviral activity of glycyrrhizic acid derivatives
438 against sars-coronavirus. J Med Chem. 2005;48(4):1256-1259.
439 44. Li SY, Chen C, Zhang HQ, Guo HY, Wang H, Wang L, Zhang X, Hua SN,
440 Yu J, Xiao PG, Li RS, Tan X. Identification of natural compounds with
441 antiviral activities against sars-associated coronavirus. Antiviral Res.
442 2005;67(1):18-23.
443 45. Wen CC, Shyur LF, Jan JT, Liang PH, Kuo CJ, Arulselvan P, Wu JB, Kuo SC,
444 Yang NS. Traditional Chinese medicine herbal extracts of Cibotium barometz,
445 Gentiana scabra, Dioscorea batatas, Cassia tora, and Taxillus chinensis
446 inhibit SARS-CoV replication. J Tradit Complement Med. 2011;1(1):41-50.
447 46. Su H, Yao S, Zhao W, Li M, Liu J, Shang W, Xie H, Ke C, Gao M, Yu K, Liu
448 H, Shen J, Tang W, Zhang L, Zuo J, Jiang H, Bai F, Wu Y, Ye Y, Xu Y.
449 Discovery of baicalin and baicalein as novel, natural product inhibitors of
450 SARS-CoV-2 3CL protease in vitro. bioRxiv. 2020:2020.2004.2013.038687.
451 47. Ding YW, Zeng LJ, Li RF, Chen QY, Zhou BX, Chen QL, Cheng PL, Wang
452 YT, Zheng JP, Yang ZF, Zhang FX. The Chinese prescription
453 lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of

20
454 viral propagation and impacts immune function. Bmc Complem Altern M.
455 2017;17(1):130.
456 48. Runfeng L, Yunlong H, Jicheng H, Weiqi P, Qinhai M, Yongxia S, Chufang L,
457 Jin Z, Zhenhua J, Haiming J, Kui Z, Shuxiang H, Jun D, Xiaobo L, Xiaotao H,
458 Lin W, Nanshan Z, Zifeng Y. Lianhuaqingwen exerts anti-viral and anti-
459 inflammatory activity against novel coronavirus (SARS-CoV-2). Pharmacol
460 Res. 2020:104761.
461 49. WHO. laboratory biosafety guidance related to the novel coronavirus (2019-
462 nCOV). 2020.
463 50. Greenhalgh T, Schmid MB, Czypionka T, Bassler D, Gruer L. Face masks for
464 the public during the COVID-19 crisis. BMJ. 2020;369:m1435.
465 51. Leung CC, Lam TH, Cheng KK. Mass masking in the COVID-19 epidemic:
466 people need guidance. Lancet. 2020;395(10228):945.
467 52. Cooke B, Ernst E. Aromatherapy: A systematic review. Br J Gen Pract.
468 2000;50(455):493-496.
469 53. Swamy MK, Akhtar MS, Sinniah UR. Antimicrobial properties of plant
470 essential oils against human pathogens and their mode of action: an updated
471 review. Evid-Based Compl Alt Med. 2016:3012462.
472

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Conflict of Interest

None of the authors has any conflict of interest.