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Medicinal Plants - Its Application As A COVID-19 Vaccine

Since the beginning of the COVID-19 epidemic, herbal traditional remedies have been employed in China. In fact, 90% of the 214 people who were treated with these medicinal herbs got better.

Also, some traditional medicinal plants protected healthy people from getting severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and helped people with moderate or severe symptoms feel better.

Similar encouraging findings have been recorded in Zhejiang Province, China. Two Chinese traditional medicines, Shu Feng Jie Du and Lianhuaqingwen, have been suggested because they have been shown to help people who have had influenza A (H1N1) or SARS-CoV-1 in the past.

The use of traditional remedies was incorporated into the recommendations for the treatment and prevention of COVID-19 by a panel of specialists from Wuhan University's Zhongnan Hospital.

Several treatments based on medicinal plants were suggested for COVID-19 prevention. Doctors also suggested that different herbal mixes be used to treat the disease at different stages.

SARS-CoV-2 is a member of the Nidovirales order of the Coronaviridae family. SARS-CoV-2 is a single (+) stranded encapsulated RNA with a symmetric helical nucleocapsid.

The virus encodes twenty proteins, including four major structural proteins (S: spike; E: envelope; M: membrane; N: nucleocapsid) and many nonstructural proteins, including RNA-dependent RNA polymerase (RdRp), coronavirus main protease (3CLpro), and papain-like protease (PLpro).

The angiotensin converting enzyme II (ACE2) was shown to be a critical functional receptor for the SARS-CoV-2, enabling it to bind to human and bat cells and hence replicate. SARS-CoV-2 attaches to host cells when the receptor binding motif—receptor binding domain (RBD) of the spike protein interacts with the ACE2 receptor.

This connection will cause the spike protein's C-terminal S2 subunit (responsible for virus-cell membrane fusion) to shift shape. The host cell-type 2II transmembrane serine protease TMPRSS2 subsequently proteolytically processes the complex S protein-ACE2, resulting in ACE2 cleavage and viral entrance into the host cell.

Following entrance and uncoating, genomic RNA is translated into two polyproteins (pp1a and pp1ab), which are proteolytically cleaved to produce 15-16 nonstructural proteins. The double-membrane vesicle is then made when the nonstructural proteins change the way the cell membrane is set up.

The genomic RNA, on the other hand, is translated into subgenomic RNA, which results in the production of structural (spike, envelope, membrane, and nucleocapsid) and auxiliary proteins. In the end, the ER-Golgi intermediate complex is where the virus is made. It is then released through the secretory route.

Natural Products With Anti-SARS-CoV-2 Effects

Runfeng et al. looked into how inhibiting and anti-inflammatory Lianhuaqingwen was against SARS-CoV-2 in 2020. Lianhuaqingwen is a combination of 11 medicinal species, a mineral remedy called gypsum, and menthol.

Traditional Chinese medicine has used Lianhuaqingwen to treat fever, cough, tiredness, flu, bronchitis, pneumonia, and the early stages of measles. It has also been part of phase II clinical studies in the US.

The Chinese National Health Commission approved this herbal combo to treat or control COVID-19. Cytopathic effect inhibition and plaque reduction tests were used to measure anti-SARS-CoV-2 activity in Vero E6 cells.

With an IC50 of 411.2 µg/ml, the herbal combination reduced SARS-CoV-2 replication in a dose-dependent manner. Furthermore, in a dose-dependent way, the combination was able to decrease the production of pro-inflammatory cytokines (TNFα-, IL-6, CCL-2/MCP-1, and CXCL-10/IP-10).

These findings might be intriguing since cytokine storms have been identified as one of the COVID-19 fatal consequences. In a prior investigation, seven compounds (arctiin, forsythoside A, gallic acid, isoliquiritigenin, kaempferol, rutin, and secoxyloganin) were shown to have significant antiviral activity, with IC50 values ranging from 4.9 ± 0.1 (kaempferol) to 47.8 ± 1.5 µM (secoxyloganin).

Wang et al. reported findings in four COVID-19 patients treated with a combination of lopinavir/ritonavir (Kaletra®) and arbidol with Shufeng Jiedu capsules (a Chinese traditional medicine).

Three individuals were confirmed to be COVID-19 negative after therapy and had substantial improvements in their symptoms. Another study on 132 COVID-19 patients in northeast Chongqing (China) found that traditional Chinese medicine was used by about 92% of them.

The research indicated that a combination of Kaletra and traditional medicine was the most effective treatment method.

Using silico techniques, Lung et al. proved that theaflavin might be employed as an important anti-SARS-CoV-2 medication. Indeed, theaflavin demonstrated promising docking affinities in the SARS-CoV-2 RNA-dependent RNA polymerase catalytic pocket.

Natural Products As ACE2-Blockers

The SARS-CoV-2 genome is able to enter host cells due to the SARS-CoV-2 spike protein attaching to host receptors. Phylogenetic analysis and key regions of ACE2 structure were used to suggest that various animals, including cats, pigeons, and sheep, would be crucial intermediate hosts for SARS-CoV-2. According to Hoffmann et al., SARS-CoV-2 enters human cells through the ACE2 receptor.

Furthermore, they revealed that TMPRSS2 inhibitors might be a potential treatment method against SARS-CoV-2. The transmembrane serine protease TMPRSS2 cleaves both ACE2 and the S protein. Ortega et al. used computer modeling to find out if changes in the SARS-CoV-2 Spike protein and the ACE2 receptor were linked.

They discovered that the SARS-CoV-2 spike protein has a higher affinity for human ACE2 than the Bat-CoV spike and ACE2. This work supported the idea that the ACE2 receptor is the main "bridge" that SARS-CoV-2 uses to spread from person to person.

Chen et al. demonstrated that, whereas SARS-CoV and SARS-CoV-2 RBD of spike glycoprotein had 72% structural similarities, SARS-CoV-2 RBD interacted more with ACE2. ACE2 inhibitors are considered to affect the RBD binding site indirectly, preventing SARS-CoV-2 infection.

Wrapp et al. discovered that the SARS-CoV-2 spike had a stronger affinity for ACE2 than the SARS-CoV. Adedeji et al. found that early inhibition of SARS-CoV by ACE2 inhibitors was one of the ways that new effective anti-SARS drugs worked.

Even so, three recent COVID-19 studies found that high blood pressure and diabetes mellitus greatly increased the chance of getting COVID-19, even when ACE2 drugs were used.

ACE2 inhibitors, angiotensin II type I receptor blockers, and ibuprofen cause ACE2 upregulation, highlighting the critical necessity of employing and/or discovering alternate ACE2 blockers.

As a result, medicinal plant-derived products or natural products that can selectively block the ACE2 receptor without inhibiting enzyme activity may be useful in preventing and/or treating SARS-CoV-2 transmission in humans without increasing ACE2 expression in patients and thus increasing COVID-19 risk.

Natural Products Targeting The TMPRSS2

The S spike proteins of SARS-CoV, MERS, and ACE2 are cleaved by the type II transmembrane serine-proteinase serine type 2 RSS2 type II transmembrane serine protease. In addition to employing an ACE2 receptor to enter host cells, SARS-CoV-2 also employs TMPRSS2 for S protein priming, according to Hoffmann et al.

The complex is broken by the TMPRSS2 after the contact between the S spike protein (SARS-CoV-2) and the ACE2 (host cell). Matsuyama and his team found that SARS-CoV-2 is especially dangerous to cells that have a lot of TMPRSS2 expression.

Since binding to the ACE2 receptor, which is cut by the TMPRSS, is a requirement for SARS-CoV-2 viral entry, drugs that stop or slow down TMPRSS2 expression in human cells could be used to treat or prevent the disease.

Several studies have shown that natural items may either downregulate or repress TMPRSS2. At 5 and 15 μM concentrations, kaempferol inhibited TMPRSS2 expression by 49.14 and 79.48%, respectively. In a similar way, it was found that sulforaphane, which is an isothiocyanate, can stop the expression of TMPRSS2 by releasing and moving Nrf2 (nuclear factor (erythroid-derived 2)-like 2).

A flavonoids mixture with standardized amounts of luteolin, quercetin, and kaempferol greatly reduced the amount of TMPRSS2 expression.Even though the three flavonoids have different effects on the body, this study found that at low doses, they have a strong synergistic effect.

However, the effectiveness and safety of these drugs in COVID-19 patients remain unknown. Furthermore, modalities of delivery, digestive system health, and illness stage may restrict the therapeutic utility of such formulations and substances. Xu et al. revealed that cryptotanshinone at 0.5 μM has anti-TMPRSS2 action.

Natural Products Targeting The Papain-Like Proteinase (Plpro)

The SARS-CoV-2 genome encodes PLpro, one of the nonstructural proteins. This protease is essential for viral replication because it helps to cleave viral polyproteins (PP1A and PP1AB) into effector proteins. Furthermore, PLpro was shown to be an opponent of the host's innate immunity.

Actually, PLpro has been demonstrated to inhibit interferon production via inhibiting IRF3 phosphorylation, dimerization, and nuclear translocation, as well as the NF-κB signaling pathways (by preventing IκBα breakdown).

These effects were seen in the pathways of Toll-like receptor 3 and retinoic acid-inducible gene 1. Furthermore, SARS-CoV PLpro has been shown to suppress the TLR7 pathway by inactivating the TRAF3/6-TBK1-IRF3/NF-κB/AP1 signaling pathways.

Arya et al. investigated the in silico inhibitory potential of PLpro in FDA-approved medicines.

They discovered that sixteen FDA-approved drugs (Biltricide, Cinacalcet, Procainamide, Terbinafine, Pethidine, Labetalol, Tetrahydrozoline, Ticlopidine, Ethoheptazine, Levamisole, Amitriptyline, Naphazoline, Formoterol, Benzylpenicillin, Chloroquine, and Chlorothiazide) exhibited significant binding affinity to SARS-Co. Disulfiram (an alcohol-aversive medication) was also shown to be a competitive inhibitor of SARS-CoV PLpro. A number of drugs have been found to inhibit the SARS-CoV PLpro.

Flavonoids From Paulownia Tomentosa (Thunb.) Steud.

Cho et al. isolated five novel granular flavonoids from Paulownia tomentosa (Thunb.) Steud. fruits: tomentin A, tomentin B, tomentin C, tomentin D, and tomentin E. These flavonoids, along with seven others previously identified, inhibited SARS-CoV PLpro in a dose-dependent way, with IC50 values ranging between 5.0 and 14.4 μM.

Tomentin E had the strongest inhibitory impact, with an IC50 of 5.0 ± 0.06 μM. Compounds containing a 3,4-dihydro-2H-pyran moiety inhibited more effectively.The flavonoids from P. tomentosa were discovered to be reversible, mixed inhibitors.

Chalcones From Angelica Keiskei (Miq.) Koidz

Park et al. evaluated the inhibitory efficacy of nine alkylated chalcones (isobavachalcone, 4-hydroxyderricin, xanthoangelol, xanthoangelol F, xanthoangelol D, xanthoangelol E, xanthoangelol B, xanthokeistal A) and four coumarins isolated from Angelica ke.

SARS-CoV PLpro was significantly suppressed by alkylated chalcones in a dose-dependent manner, with an IC50 ranging from 1.2 ± 0.4 to 46.4 ± 7.8 µM. However, none of the coumarins tested showed a substantial inhibitory impact on SARS-CoV PLpro.

Isobavachalcone was shown to be a mixed inhibitor in kinetic experiments, while the other chalcones were noncompetitive. Interestingly, xanthoangelol E, an OOH substituted counterpart, had the highest inhibitory effect (IC50 = 1.2 ± 0.4 µM).

Different plants and laying close to each other on a wooden platform
Different plants and laying close to each other on a wooden platform

Tanshinones From Salvia Miltiorrhiza Bunge

The ethanolic extract of Salvia miltiorrhiza Bunge (30 g/µml) inhibited SARS-CoV PLpro by 88%. In the n-hexane fraction, there were also seven bioactive tanshinones: tanshinone IIA, tanshinone IIB, methyl tanshinonate, cryptotanshinone, tanshinone I, dihydrotanshinone I, and rosmariquinone.

Using a fluorometric assay, several tanshinones were tested for inhibition of SARS-CoV PLpro activity. Both compounds displayed significant inhibitory time-dependent actions, with IC50 values ranging from 0.8 to 30 µM. The structure dimethyl tetrahydronaphthalen was linked to increased inhibitory potential.

The findings revealed that cryptotanshinone was the most effective inhibitor of SARS-CoV PLpro, with binding IC50 of 0.8 ± 0.2 µM. Rosmariquinone was shown to be a mixed-type inhibitor of SARS-CoV PLpro, while the other tanshinones were noncompetitive inhibitors.

Diarylheptanoids From Alnus Japonica (Thunb.) Steud

Park et al. employed activity-guided fractionation to isolate nine diarylheptanoids from the ethanol extract of Alnus japonica (Thunb.) Steud (platyphyllenone, hirsutenone, platyphyllone, platyphyllonol-5-xylopyranoside, hirsutanonol, oregonin, rubranol, rubranoside B, and rubranoside They used a continuous fluorometric test to assess its SARS-CoV PLpro inhibiting impact.

The findings demonstrated that hirsutenone, hirsutanonol, oregonin, rubranol, rubranoside B, and rubranoside A inhibited SARS-CoV PLpro in a dose-dependent manner, with IC50 values ranging from 3 to 44.5 µM. Hirsutenone had the strongest inhibitory impact, with an IC50 of 4.1 ± 0.3 µM, which was less than that of the reference inhibitor curcumin (5.7 µM). The inclusion of α,β-unsaturated carbonyl and catechol groups seems to be connected to the higher inhibitory activity of diarylheptanoids.

People Also Ask

What Are Two Medicinal Plants?

Medicinal plants including Aloe, Tulsi, Neem, Turmeric, and Ginger treat a variety of diseases. In many regions of the nation, they are considered home cures. It is well known that many people use Basil (Tulsi) to make medications, black tea, for pooja, and for various purposes in their daily lives.

Which Flower Is Used As A Medicinal Plant?

Flowers: Plant flowers have long been used in traditional medicine. Clove and chamomile blossoms are two examples. Flower components such as saffron stamens, maize stigmas, and pollen are also employed. Fruits have long been utilized for therapeutic reasons.

Is Rose A Medicinal Plant?

The rose plant has several medical qualities, making it an excellent blood cleanser. This plant's anti-inflammatory and aphrodisiac properties help with a variety of health concerns such as intestinal ulcers and diarrhea. The whole plant has been utilized for therapeutic reasons in Ayurveda.

How Many Medicinal Plants Are There?

Worldwide, between 50,000 and 80,000 flowering plant species are utilized for therapeutic reasons, according to the International Union for Conservation of Nature and the World Wildlife Fund.


Medicinal plants and natural products are still seen as potential solutions for illness prevention and treatment. Since the COVID-19 pandemic's emergence in December 2019, numerous traditional herbal medications have been utilized with favorable health outcomes among COVID-19 patients, mostly in China.

Although studies on the anti-SARS-CoV-2 effects of medicinal plants are still insufficient and relatively immature, some natural products with IC50 values less than 10 µM could be considered promising anti-SARS-CoV-2 agents due to their ability to block its life-cycle related proteins such as the cellular receptor ACE2, papain-like or chymotrypsin-like proteinases.

Several constraints have been identified, including the specificity of the effect exerted by such items, the sustainable procurement of the species, the dosage range employed, and the application of adequate controls.

While existing research suggests that plant-derived products may aid in the battle against COVID-19, further research is needed to determine the therapeutic utility of such medicines against COVID-19 infection.

Aside from the necessity for clinical confirmation of their effectiveness and safety, the bioavailability of natural compounds with potential anti-SARS-CoV-2 properties, such as tannins, should be studied.

About The Authors

Suleman Shah

Suleman Shah - Suleman Shah is a researcher and freelance writer. As a researcher, he has worked with MNS University of Agriculture, Multan (Pakistan) and Texas A & M University (USA). He regularly writes science articles and blogs for science news website immersse.com and open access publishers OA Publishing London and Scientific Times. He loves to keep himself updated on scientific developments and convert these developments into everyday language to update the readers about the developments in the scientific era. His primary research focus is Plant sciences, and he contributed to this field by publishing his research in scientific journals and presenting his work at many Conferences. Shah graduated from the University of Agriculture Faisalabad (Pakistan) and started his professional carrier with Jaffer Agro Services and later with the Agriculture Department of the Government of Pakistan. His research interest compelled and attracted him to proceed with his carrier in Plant sciences research. So, he started his Ph.D. in Soil Science at MNS University of Agriculture Multan (Pakistan). Later, he started working as a visiting scholar with Texas A&M University (USA). Shah’s experience with big Open Excess publishers like Springers, Frontiers, MDPI, etc., testified to his belief in Open Access as a barrier-removing mechanism between researchers and the readers of their research. Shah believes that Open Access is revolutionizing the publication process and benefitting research in all fields.

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