During the SARS outbreak in 2003, China effectively combined conventional medicine with Traditional Chinese Medicine also known as TCM. Due to its pathbreaking effectiveness, Chinese authorities employed Traditional Chinese Medicine in the treatment of COVID-19 as well. At a press conference in Februay, Chinese officials reported to the world how they treated more than 85% of the COVID-19 patients with TCM.
Potential use of Medicinal Plants against SARS-COV-2
Since the outbreak of Coronavirus disease (COVID-19) caused by SARS-CoV-2, there has been no vaccine or specific antiviral medication for treatment of the infection where supportive care and prevention of complications is the current management strategy.
In this work (read full study below), the potential use of medicinal plants and more than 16,500 of their constituents was investigated within two suggested therapeutic strategies in the fight against SARS-CoV-2.
These strategies include the prevention of SARS-CoV-2 RNA synthesis and replication, through targeting vital proteins and enzymes as well as modulation of the host’s immunity through production of virulence factors.
Therapeutic Strategies in prevention of COVID-19
Currently, there are no vaccines or specific antiviral medication to treat SARS-CoV-2 infections. Therefore, supportive care and prevention of complications is an important management strategy to minimize harm.
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Suggested therapeutic strategies in the fight against SARS-CoV-2 can be split into 4 different categories:
- prevention of SARS-CoV-2 RNA synthesis and therefore replication, through action on vital proteins and enzymes,
- impeding virus-cell receptor binding or suppression of virus self-assembly,
- stimulation of the host’s immunity through production of virulence factors and
- blocking the entry of the virus into host cells through action on the host’s enzymes or cellular entry receptor.
Traditional Chinese Medicine (TCM)
For centuries, natural products have been a rich source of medicinally active constituents that have had a pivotal role in treating and preventing an infinite number of diseases.
Natural products are a cornerstone of Traditional Chinese Medicine (TCM), which encompasses a tremendous wealth of ancient knowledge.
The importance of TCM in emerging pandemics was made evident when it was effectively partnered with conventional medicine in the management of the SARS outbreak in 2003.
Therefore, due to their notable contributions in the SARS-CoV pandemic, the National Health Commission of the People’s Republic of China employed TCM in the COVID-19 treatment guidelines.
At a press conference held on February 17, an official reported that 60,107 COVID-19 cases (85.2% of total cases at the time) were treated with TCM.
Within this context, the potential of the use of medicinal plants in the mitigation of the novel SARS-CoV-2 infection has been investigated.
Molecular Docking Studies
A database comprising more than 16,000 compounds was compiled and docked against the crucial viral proteins; 3-chymotypsin protease (3CLpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp) to find potential inhibitors for these enzymes.
Furthermore, network pharmacology analysis of all the compounds in the database was attempted to speculate those that can target the inflammatory and immunity-related pathways at the molecular level and revealing those plants with potential multi-components and multi-targets that may help regulate the body functions and possibly will play a therapeutic role in the mitigation of the disease.
Medicinal Plants & Immune Regulation Pathways
Huge inflammatory response is observed in COVID-19 and in several clinical trials, it has been shown that combination of anti-inflammatory and antiviral drugs may be more effective than each one individually.
One of the main mechanisms involved in the SARS-CoV-2 induced-ARDS is the cytokine storm, the deadly uncontrolled systemic inflammatory response resulting from the release of large amounts of pro-inflammatory cytokines.
Therefore, arbitration of the immune evasion of SARS-CoV-2 is imperative in its treatment and specific drug development.
Targeting this approach by medicinal plants and their constituents and identifying their potential inflammation and immunity-correlated target proteins and pathways was also the focus of this study.
Network Pharmacology Analysis
Many of the medicinal plants and their constituents have a potential for use in the mitigation of the new SARS-CoV-2 infection.
Herein, a database comprised of more than 16,500 compounds was screened against the three viral targets 3CLpro, PLpro and RdRp, and several constituents identified may inhibit SARS-CoV-2 activity through inhibition of virus replication.
A network pharmacology analysis was performed for all the plants constituents and revealed that several compounds possessed multi-targets and enriched pathways of the molecular targets including cytokine–cytokine receptor interaction, TNF signaling pathway, Toll-like receptor signaling pathway, NF-kappa B signaling pathway, and JAK-STAT3 signaling pathway.
Mitigating SARS-CoV-2 through TCM
These results suggest a potential role of medicinal plants in the management of the current SARS-CoV-2 infection. A special emphasis is paid to the plant Glycyrrhiza glabra (liquorice) which has a long history of use in treatment of several viral infections.
In fact, randomized controlled trials confirmed that the Glycyrrhiza glabra demonstrated a reduction of mortality and viral activity in SARS-CoV-2 related coronavirus.
Meanwhile, the plants Hibiscus sabdariffa and Cichorium intybus are rich sources of caffeic acid derivatives which have been widely investigated concerning their antiviral potential.
The performed network pharmacology analysis revealed the synergistic nature of the compounds within each medicinal plant.
Combination of the most enriched plants in the created network i.e. Glycyrrhiza glabra (liquorice), Hibiscus sabdariffa, Cichorium intybus, could be chosen for mitigation of SARS-CoV-2.
Further molecular dynamic simulation studies, in vitro and in vivo analyses are required to confirm the results of the study, however, the insights provided by the present study may substantiate valuable exploration and development of anti-SARS-CoV-2 therapeutic agents from natural origin.