Researchers at Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego have broken down the genomic and life history traits of three classes of viruses that have caused endemic and global pandemics in the past and identify natural products – compounds produced in nature – with the potential to disrupt their spread.
In a review appearing in the Journal of Natural Products, marine chemists Mitchell Christy, Yoshinori Uekusa, and William Gerwick, and immunologist Lena Gerwick describe the basic biology of three families of RNA viruses and how they infect human cells.
These viruses use RNA instead of DNA to store their genetic information, a trait that helps them to evolve quickly. The team then describes the natural products that have been shown to have capabilities to inhibit them, highlighting possible treatment strategies.
“We wanted to evaluate the viruses that are responsible for these deadly outbreaks and identify their weaknesses,” said Christy, the first author. “We consider their similarities and reveal potential strategies to target their replication and spread. We find that natural products are a valuable source of inhibitors that can be used as a basis for new drug development campaigns targeting these viruses.”
The research team is from Scripps Oceanography’s Center for Marine Biotechnology and Biomedicine (CMBB), which collects and analyzes chemical compounds found in marine environments for potential efficacy as antibiotics, anticancer therapies, and other products with medical benefit.
A drug known as Marizomib entered the final stages of clinical trials as a potential treatment for brain cancers earlier in 2020. The drug came from a genus of marine bacteria that CMBB researchers had originally collected in seafloor sediments in 1990.
The researchers, funded by the National Institutes of Health and the UC San Diego Chancellor’s Office, present an overview of the structure of viruses in the families Coronaviridae, Flaviviridae, and Filoviridae.
Within these families are viruses that have led to COVID-19, dengue fever, West Nile encephalitis, Zika, Ebola, and Marburg disease outbreaks.
The team then identifies compounds produced by marine and terrestrial organisms that have some demonstrated level of activity against these viruses. Those compounds are thought to have molecular architectures that make them potential candidates to serve as viral inhibitors, preventing viruses from penetrating healthy human cells or from replicating.
The goal of the review, the researchers said, was to improve the process of drug development as new pandemics emerge, so that containing disease spread can accelerate in the face of new threats.
“It is simply common sense that we should put into place the infrastructure necessary to more rapidly develop treatments when future pandemics occur,” the review concludes.
“One such recommendation is to create and maintain international compound libraries with substances that possess antiviral, antibacterial, or antiparasitic activity.”
To achieve that goal, the researchers realize that international agreements would need to be reached to address intellectual property issues, the rights and responsibilities of researchers, and other complex issues.
And while there has been remarkable progress in the development of vaccines for SARS-CoV-2 infection, effective antiviral drugs are also critically needed for managing COVID-19 infection in unvaccinated individuals or in cases where the efficacy of a vaccine decreases over time, the researchers said.
While several candidate antiviral molecules have been investigated for use in the clinic, such as remdesivir, lopinavir-ritonavir, hydroxychloroquine, and type I interferon therapy, all have shown limited or no efficacy in large scale trials. Effective antiviral drugs are still much in need of discovery and development.
Chinese herbal medicines and natural compounds possess promising antiviral effects against Human coronaviruses (HCoVs) and provide a rich resource for novel antiviral drug development. This review provides an update on natural compounds against HCoVs and summarizes the active natural compounds and their possible action mechanisms.
Antiviral properties of natural products against coronavirus
Extensive studies have been conducted over the past years to identify anti-CoV agents from natural products and Chinese herbal medicine39. In this section, we discuss the medicinal plant-based natural compounds and traditional Chinese medicine (TCM) formulae with antiviral action against coronaviruses and their potential for use in clinical practice.
Natural products against CoVs
Various natural products have shown potent antiviral effects against SARS-CoV40, 41, 42, 43, MERS-CoV44, HCoV-229 E45 and HCoV-OC4346. Aescin isolated from Aesculus hippocastanum and reserpine isolated from various Rauwolfia species40, were both shown to have significant anti-SARS activities with the concentration for 50% of maximal effect (EC50) values of 3.4 and 6.0 μmol/L, respectively41.
Ginsenoside-Rb1, one of the pharmacologically active components of Panax ginseng47, was reported to possess activity against SARS-CoV at the concentration of 100 μmol/L41. Boenninghausenia sessilicarpa (Rutaceae), a slender and perennial plant, has long been known as a coumarin-rich Chinese herbal medicine distributed in the temperate hilly regions at an altitude of 1500–2500 m in southwestern China.
It is traditionally used for the treatment of fever, festers and tonsillitis. Leptodactylone, extracted from B. sessilicarpa, was found to have a strong protective effect against virus-infected cells and anti-SARS-CoV activity with the inhibition rate of 60% at 100 mg/mL42. It has also been shown that lycorine extracted from Lycoris radiata was identified to have anti-SARS-CoV activity with EC50 value of 15.7 ± 1.2 nmol/L43.
Latest study of repurposing of clinically approved drugs for treatment of COVID-19 showed that cepharanthine, a bisbenzylisoquinoline alkaloid from tubers of Stephania japonica (Qianjinteng), exhibited a potent inhibition of a 2019-nCoV-related pangolin coronavirus GX_P2V infection, with EC50 value of 0.98 μmol/L using a 2019-novel coronavirus-related coronavirus model48. Dihydrotanshinone is a major lipophilic compound isolated from Salviae Miltiorrhizae Radix et Rhizoma, which is commonly used in TCM.
A recent study showed that dihydrotanshinone exerted inhibitory effects against viral entry in the MERS-CoV with the IC50 value of 1 μg/mL44. Saikosaponin B2, isolated from Bupleuri Radix, exerted potent antiviral activity against HCoV-22E9, with the IC50 value of 1.7 ± 0.1 μmol/L45.
The antiviral action mechanism of saikosaponin B2 may be mediated, at least in part, by inhibiting viral attachment to cells, blocking viral penetration into cells, and interfering with the early stage of viral replication, such as virus absorption and penetration. Tetrandrine, isolated from Stephaniae Tetrandrae Radix, has been found to dramatically suppress the replication of HCoV-OC43, with the IC50 value of 0.33 ± 0.03 μmol/L46.
All these natural compounds possess antiviral effects against the coronavirus, and their action mechanisms were summarized in Table 129,30,41, 42, 43, 44, 45, 46,48, 49, 50, 51, 52, 53, 54, 55, 56, 57, while their chemical structures shown in Fig. 2. This article also reported the IC50 values of the natural products against the HCoVs including SARS and MERS.
As shown in Table 1, the IC50 values of these compounds mostly ranged from micro to milligrams per milliliter, or from nano to micromoles per liter. These natural compounds have been reported to act on various viral targets such as spike (S) glycoprotein, coronavirus main proteinase-chymotrypsin-like protease (3CLpro), the papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), and nucleocapsid (N) proteins. These pharmacological targets are further discussed in the section below.
Summary of the anti-CoVs effects of natural compounds and their possible action mechanisms.
|Plant||Compound||Virus acting on||IC50 value||Reported antiviral mechanism||Ref.|
|Licorice root||Glycyrrhizin||SARS-CoV||300 mg/L||Upregulates nitrous oxide synthase and nitrous oxide production||29,49|
|Panax ginseng||Ginsenoside-Rb1||SARS-CoV||100 μmol/L||Inhibits glycoprotein activity||41|
|Rauvolfia serpentina||Reserpine||SARS-CoV||6.0 μmol/L||–||41|
|Aesculus hippocastanum||Aescin||SARS-CoV||3.4 μmol/L||–||41|
|Boenninghausenia sessilicarpa||Leptodactylone||SARS-CoV||100 μg/mL||–||42|
|Lycoris radiata||Lycorine||SARS-CoV||15.7 ± 1.2 nmol/L||–||43|
|Salvia miltiorrhiza||Dihydrotanshinone||MERS-CoV||1 μg/mL||–||44|
|Bupleurum chinense||Saikosaponin B2||HCoV-229E||1.7 ± 0.1 μmol/L||Interferes with events of early viral entry||43,45|
|Stephania tetrandra||Tetrandrine||HCoV-OC43||0.33 ± 0.03 μmol/L||Inhibits p38 MAPK pathway||46|
|Stephania japonica||Cepharanthine||SARS-CoV-2||0.98 μmol/L||ACE inhibitor||48|
|Rheum palmatum||Emodin||SARS-CoV||200 μmol/L||Blocks the binding of S protein to ACE2||50|
|Triterygium regelii||Celastrol||SARS-CoV||10.3 μmol/L||Inhibits SARS-CoV 3CLpro||51|
|Triterygium regelii||Pristimererin||SARS-CoV||5.5 μmol/L||Inhibits SARS-CoV 3CLpro||51|
|Triterygium regelii||Tingenone||SARS-CoV||9.9 μmol/L||Inhibits SARS-CoV 3CLpro||51|
|Triterygium regelii||Iguesterin||SARS-CoV||2.6 μmol/L||Inhibits SARS-CoV 3CLpro||51|
|Ginkgo biloba||Quercetin-3-β-galactoside||SARS-CoV||42.79 ± 4.97 μmol/L||Competitively inhibits SARS-CoV 3CLpro||52|
|Salvia miltiorrhiz||Tanshinones I–VII||SARS–CoV||0.7–30 μmol/L||Inhibits PLpro activity||53|
|Alnus japonica||Hirsutenone||SARS-CoV||4.1 μmol/L||Inhibits PLpro activity||53,54|
|Black tea||Theaflavin||SARS-CoV-2||–||Inhibits RdRp activity||55|
|Myrica rubra||Myricetin||SARS-CoV||2.71 ± 0.19 μmol/L||Inhibits ATPase activity||56|
|Scutellaria baicalensis||Scutellarein||SARS-CoV||0.86 ± 0.48 μmol/L||Inhibits ATPase activity||56|
|Angelica keiskei||Chalcones I–IX||SARS–CoV||11.4–129.8 μmol/L||Competitively inhibits SARS-CoV 3CLpro|
Chinese herbal formulae against CoVs
TCM has been used for the treatment of epidemic diseases for a long history and accumulated rich experience. Thus, the antiviral activities are not limited to natural compounds, and also extended to TCM formulae. For example, Lian-Hua-Qing-Wen Capsule (LHQWC, Clearing Pestilential Disease with Forsythiae Fructus-Lonicerae Capsule), a commonly used Chinese medicine preparation, is widely used in clinical practice to treat viral influenza, and plays a very important role in the fight against SARS-CoV58, 59, 60 in particular.
LHQWC has been reported to exert inhibitory effects on the SARS-CoVs in cultured Vero-E6 cells, with the EC50 value of 0.11 mg/mL61. LHQWC ameliorated the clinical symptoms such as fever, cough, fatigue and shortness of breath in 63 patients with COVID-1962. A recent study by Academician Nanshan Zhong revealed that LHQWC significantly inhibited the SARS-CoV-2 replication with the IC50 value of 411.2 μg/mL, affected virus morphology, and exerted anti-inflammatory activity in vitro63.
They also conducted a prospective multicenter open-label randomized controlled trial on the effectiveness of LHQWC in 284 confirmed cases of COVID-19 (142 each in treatment and control group). The results showed that COVID-19 patients treated with LHQWC for 14 days resulted in a significantly higher recovery rate (91.5% vs. 82.4%, P = 0.022), a markedly shorter median time to symptom recovery (7 vs. 10 days, P < 0.001), as well as a dramatically shorter time to recovery of fever (2 vs. 3 days), fatigue (3 vs. 6 days) and coughing (7 vs. 10 days) (P < 0.001 for all) than the control group (baseline treatment).
The results of this trial amply attested the safety and efficacy of LHQWC in patients with COVID-1964. In a retrospective clinical analysis, it was revealed that LHQWC could significantly ameliorate the major symptoms associated with the novel coronavirus-infected pneumonia (NCIP) patients by shortening the duration of fever and cough, and improving the recovery rate65.
Moreover, the functional indications of LHQWC have been added to the originally approved indications for COVID-19 treatment. LHQWC can be used to treat clinical symptoms such as fever, cough, and fatigue for the light and common types of COVID-19 patients66.
As revealed by network pharmacology approach, Ren-Shen-Bai-Du-San (Ginseng to Defeat Toxicity Powder) may inhibit the cytokine storm formation in COVID-19 patients through regulating chemokines, increasing blood oxygen saturation, inhibiting signal transducer and activator of transcription (STAT), mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), phosphoinositide 3-kinases (PIK3K) and interleukin-6 (IL-6) signaling pathways67.
Another TCM formula, Qing-Fei-Jie-Du Decoction (Decoction for Clearing the Lung and Detoxification) was used for the prevention and treatment of SARS68 and also recommended for COVID-19 treatment according to the 7th edition of the Guidelines of Diagnosis and Treatment for COVID-1969 issued by the National Health Commission of China.
Based on this latest edition of the Guidelines, several TCM formulae were recommended for the prevention and treatment of patients with COVID-19, including Jin-Hua-Qing-Gan Granule70,71 (Lonicerae Flos for Clearing Influenza Granule), Huo-Xiang-Zheng-Qi Water (Agastaches Herba Qi-Correcting Water), Shu-Feng-Jie-Du Capsule72, 73, 74 (Wind-Expelling and Detoxification Capsule), Xue-Bi-Jing Injection75 (Blood Definitely Be Cleansed Injection Fluid) and other herbal formulae (as shown in Table 258, 59, 60,62,67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81).
Among the components of these formulae, Rhei Radix et Rhizoma, Scutellariae Radix, Glycyrrhizae Radix et Rhizoma, Bupleuri Radix, Lonicerae Japonicae Flos, Isatidis Radix and Houttuyniae Herba have been found to exert antimicrobial activities.
Chinese herbal formulae used for the treatment of SARS-CoV and COVID-19.
|Type of virus||TCM formulae||Constituent||Ref.|
|SARS-CoV COVID-19||Lian-Hua-Qing-Wen Capsule||Forsythiae Fructus, Lonicerae Japonicae Flos, Ephedrae Herba, Armeniacae Semen Amarum, Isatidis Radix, Dryopteridis Crassirhizomatis Rhizoma, Houttuyniae Herba, Pogostemonis Herba, Rhei Radix et Rhizoma, Rhodiolae Crenulatae Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma and Gypsum Fibrosum||58, 59, 60,62|
|COVID-19||Ren-Shen-Bai-Du-San||Bupleuri Radix, Peucedani Radix, Notopterygii Rhizoma et Radix, Platycodonis Radix, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Poria, Chuanxiong Rhizoma, Aurantii Fructus, Angelicae Pubescentis Radix||67|
|SARS-CoV||Qing-Fei-Jie-Du Decoction||Astragali Radix, Bupleuri Radix, Ephedrae Herba, Armeniacae Semen Amarum, Gypsum Fibrosum, Coicis Semen, Trichosanthis Pericarpium, Platycodonis Radix, Menthae Haplocalycis Herba, Scutellariae Radix, Glycyrrhizae Radix et Rhizoma, Lonicerae Japonicae Flos, and Artemisiae Annuae Herba||68|
|SARS-CoV COVID-19||Jin-Hua-Qing-Gan Granule||Lonicerae Japonicae Flos, Gypsum Fibrosum, Ephedrae Herba, Armeniacae Semen Amarum, Scutellariae Radix, Forsythiae Fructus, Fritillariae Thunbergii Bulbus, Anemarrhenae Rhizoma, Arctii Fructus, Artemisiae Annuae Herba, Menthae Haplocalycis Herba, Glycyrrhizae Radix et Rhizoma||69, 70, 71|
|SARS-CoV COVID-19||Shu-Feng-Jie-Du Capsule||Patriniae Herba, Isatidis Radix, Bupleuri Radix, Glycyrrhizae Radix et Rhizoma, Polygoni Cuspidati Rhizoma et Radix, Forsythiae Fructus, Phragmitis Rhizoma, Verbenae Herba||72, 73, 74|
|COVID-19||Xue-Bi-Jing Injection||Carthami Flos, Paeoniae Radix Rubra, Chuanxiong Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Angelicae Sinensis Radix||75|
|SARS-CoV||Ma-Xing-Shi-Gan Decoction||Ephedrae Herba, Armeniaca Semen Amarum, Gypsum Fibrosum, Glycyrrhizae Radix et Rhizoma||76,77|
|SARS-CoV||Shuang-Huang-Lian Granule||Lonicerae Japonicae Flos, Scutellariae Radix, Forsythiae Fructus||78,79|
|SARS-CoV||Yin-Qiao Powder||Forsythiae Fructus, Lonicerae Japonicae Flos, Platycodonis Radix, Menthae Haplocalycis Herba, Lophatheri Herba, Glycyrrhizae Radix et Rhizoma, Schizonepetae Spica, Sojae Semen Praeparatum, Arctii Fructus, Phragmitis Rhizoma||80,81|
The targets of natural products against CoVs
Natural products alone and TCM herbal formulae have antiviral activities against coronaviruses through acting on different molecular targets. We summarized the molecular targets of natural products against coronavirus, and these targets include S glycoprotein, coronavirus main 3CLpro, PLpro, RdRp, N proteins and other kinase such as viral helicase.
Targeting on S glycoprotein
The coronavirus spike (S) glycoprotein is the main antigen presented at the viral surface and is the target of neutralizing antibodies during infection, and a focus of vaccine design. S is a class I viral fusion protein synthesized as a single polypeptide chain precursor of approximately 1300 amino acids.
For many coronaviruses, S is processed by host proteases to generate two subunits, designated S1 and S2, which remain non-covalently bound in the pre-fusion conformation82. The size of the abundantly N-glycosylated S protein varies greatly between CoV species ranging from approximately 1100 to 1600 residues in length, with an estimated molecular mass of up to 220 kDa. Trimers of the S protein form the 18−23-nm long, club-shaped spikes that decorate the membrane surface of the CoV particle.
Besides being the primary determinant in CoV host tropism and pathogenesis, the S protein is also the main target for neutralizing antibodies elicited by the immune system of the infected host83. The CoV S protein is responsible for host cell attachment and mediates host cell membrane and viral membrane fusion during infection, the two key steps in the viral life cycle and major targets for antiviral drugs and vaccines35,84.
Various antiviral natural compounds act on antiviral S glycoprotein. For instance, emodin, the major component of Rhei Radix et Rhizoma, has been demonstrated to possess antiviral effects against SARS-CoV via targeting S protein and blocking the binding of S protein to ACE2 in a dose-dependent manner50,85. Extracts of Eucalyptus globulus and Lonicera Japonica Flos, as well as ginsenoside-Rb1 have been reported to possess antiviral activity against SARS-CoV due to their ability to disrupt the envelope glycoprotein processing41,43.
Saikosaponins isolated from Bupleuri Radix exerted antiviral activity against HCoV-22E9. More specifically, saikosaponin B2 possessed potent anti-CoV activity via affecting the viral penetration process including viral attachment and penetration through disturbing viral glycoproteins45. Bis-benzylisoquinoline alkaloids-tetrandrine from Stephaniae Tetrandrae Radix dramatically suppressed the replication of HCoV-OC4346 via targeting S protein.
Targeting on 3CLpro and PLpro
3CLpro and PLpro are two proteases that process the polypeptide translation product from the genomic RNA into the structural and nonstructural protein components, which are vital for the replication and packaging of a new generation of viruses. 3CLpro is an essential part of the polyprotein and is usually present as a monomer. However, upon substrate binding, dimer formation has been observed.
Each monomer has two domains (I and II) along with a C-terminal domain. 3CLpro is an important drug target, as its protease activity is crucial for viral survival and replication86. PLpro enzyme has two distinct functions in viral pathogenesis. The first one is to process the viral polyprotein into individual proteins that are essential for viral replication.
The second is to remove ubiquitin and ISG15 proteins from host cell proteins, which likely helps coronaviruses shun the host’s innate immune response87. Both 3CLpro and PLpro are essential to the virus for replication and controlling the host cell, and are viable targets for antiviral agents88,89.
The important functions of 3CLpro and PLpro in the life cycle of virus render them the key viable targets for the development of anti-SARS therapeutics. Numerous promising candidates have been reported to kill the virus via targeting 3CLpro and PLpro. For example, chalcones, flavanones and coumarins from Angelicae Sinensis Radix showed dose-dependent inhibitory effects against SARS-CoV by inhibiting the activity of 3CLpro.
In addition, natural compounds such as hesperetin and sinigrin isolated from Isatidis Radix90, celastrol, pristimererin, tingenone and iguesterin isolated from Triterygium regelii51 and quercetin derivatives quercetin-3-β-galactoside52 have antiviral activities against SARS-CoV through targeting on SARS-CoV 3CLpro. Moreover, tanshinone I isolated from Salviae Miltiorrhizae Radxi et Rhizoma53 and hirsutenone isolated from Alnus japonica54 exhibited dose-dependent inhibitory effects against SARS-CoV through targeting PLpro, with the IC50 values of 0.7 and 4.1 μmol/L, respectively.
Targeting on RdRp
RdRp, also called RNA replicases, is an important protease that catalyzes the replication of RNA from RNA template and is an essential protein encoded in the genomes of all RNA-containing viruses with no DNA stage. An RdRp is involved in a pathway outside the “central dogma” of early molecular biology. RdRps, present in a wide variety of RNA viruses, are involved in genome replication, mRNA synthesis, and RNA recombination.
They are essential for the survival of viruses91. RdRp has served as an excellent antiviral target against coronaviruses, and many promising naturally-occurring chemical principles exhibit their antiviral properties via targeting RdRp. For instance, theaflavin markedly suppressed SARS-CoV-2 replication through inhibiting RdRp55. Houttuyniae Herba also exhibited significant inhibitory effects against SARS-CoV via suppressing the activities of SARS-CoV 3CLpro and RdRp92.
Targeting on N proteins
The N protein is the only structural protein that is associated with RTCs. It binds to the gRNA, and is essential for the incorporation of the virus genetic material into CoV particles. Moreover, it is the major component of ribonucleoprotein complex sitting in the virion cores, and thus also plays an essential architectural role in the virus particle structural organization through a network of interactions with the gRNA, M protein and other N molecules.
For CoVs, N protein primarily encapsidates the viral genome but also plays an important role in viral replication, virus particle assembly and release93,94. Due to its pivotal role in the incorporation of the virus genetic material into CoV particles, it has been recognized as an important target for various antiviral compounds.
Resveratrol, a well-known natural compound widely presented in different plants, including Vitis vinifera, Polygonum cuspidatum and Vaccinium macrocarpon, has been demonstrated to decrease the production of nitric oxide in tissue to reduce inflammation95,96.
It also acts as an antioxidant to remove free radicals to suppress tumor growth97 and treat age-related diseases98,99. Moreover, resveratrol has been shown to have antiviral activity on MERS-CoV via targeting N protein and prolong cellular survival after viral infection30.
Besides targeting S protein, 3CLpro, PLpro, RdRp, and N proteins, natural products can also target on other proteins to exert their anti-CoV activities. Glycyrrhizin, an active ingredient of Glycyrrhizae Radix et Rhizoma, has been observed to exert anti-SARS-CoV activity through targeting protein kinase C, which upregulates the nitrous synthase and production29,49.
Viral helicase is essential for subsequent viral replication and proliferation, and is considered as a potential target for antiviral therapy100. Natural compounds such as myricetin and scutellarein, potently inhibited the SARS-CoV helicase protein by affecting the ATPase activity56.
The potential of natural compounds for clinical treatment of COVID-19
As shown in Fig. 3, CoV relies on its spike proteins to bind to the host cell surface receptor for entry. For SARS-CoV-2, it is now known that this receptor is ACE2101. After the virus entries into the host cell, its positive genomic RNA attaches directly to the host ribosome for the translation of two large, coterminal polyproteins that are processed by proteolysis into components for packaging new virions.
Two proteases that participate in this proteolysis process are 3CLpro and PLpro. In order to replicate the RNA genome, the CoV encodes a replicase that is a RdRp. These four proteins are essential for the pathogenicity of virus. Therapeutics currently targeting spike, RdRp, 3CLpro, and PLpro are possible treatments for SARS-CoV-2102.
Moreover, the initial analyses of genomic sequences from COVID-19 patients indicate that the catalytic sites of the four COVID-19 enzymes that could represent antiviral targets are highly conserved and share a high level of sequence similarity with the corresponding SARS and MERS enzymes. SARS-CoV-2 shares 82% similarity of sequence identity with SARS-CoV and more than 90% similarity of sequence identity in several essential enzymes103.
Therefore, it is rational to consider repurposing existing MERS and SARS inhibitors for COVID-19 treatment102. As listed in Table 1, natural compounds such as theaflavin and cepharanthine suppressed SARS-CoV-2 by suppressing RdRp and ACE activities; hirsutenone and tanshinones I–VII showed antiviral action against SARS-CoV via inhibiting the PLpro activity, while celastrol, pristimererin, tingenone, iguesterin, chalcones I–IX and quercetin-3-β-galactoside were able to inhibit SARS-CoV by suppressing the 3CLpro activity.
Owing to the close resemblance between SARS-CoV and SARS-CoV-2, all these natural compounds and their original plants with the antiviral activities against SARS-CoV and MERS-CoV may have potential protective effects against COVID-19.
reference link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278644/
More information: Mitchell P. Christy et al, Natural Products with Potential to Treat RNA Virus Pathogens Including SARS-CoV-2, Journal of Natural Products (2020). DOI: 10.1021/acs.jnatprod.0c00968