Could an over-the-counter health “shot” help fight COVID-19?
George Mason University researchers think it just might.
Cell and Bioscience recently highlighted research led by Yuntao Wu and Ramin Hakami in which they examined the potential anti-coronavirus activities of an over-the-counter drink called Respiratory Detox Shot (RDS).
RDS is a remedy containing nine herbal ingredients traditionally used in Eastern medicine to manage lung diseases. The researchers reported that RDS inhibited the infection of target cells by SARS-CoV and SARS-CoV-2 pseudoviruses and by infectious wild-type SARS-CoV-2.
Their results suggest that RDS might broadly inhibit respiratory viruses, such as influenza.
SARS-CoV is the viral pathogen causing Severe Acute Respiratory Syndrome (SARS), and its sister virus, SARS-CoV-2, is the pathogen that causes COVID-19. The COVID-19 global pandemic is a major focus of researchers around the world.
While effective vaccines have been developed, there is still a need for developing effective treatments. In particular, new variants of the virus are continuously emerging, and some of these variants may make the vaccines less effective.
Ramin Hakami, an associate professor in Mason’s School of Systems Biology and one of the authors of the study, said that the fact that RDS is a drinkable food supplement is helpful.
“If it proves effective in vivo, it should be a treatment for COVID-19 that is easy to administer,” said Hakami, who also works at Mason’s National Center for Biodefense and Infectious Diseases. “That’s a big plus.”
For their study, Hakami, Wu, and Mason researchers Brian Hetrick, Adeyemi A. Olanrewaju, Linda D. Chillin, Sijia He, and Deemah Debbagh worked with Dongyang Yu of Virongy LLC, Yuan-Chun Ma of Dr. Ma’s Laboratories Inc., and Lewis A. Hoffman of the World Health Science Organization.
For the study, they pretreated cells with diluted RDS and then infected the cells in the presence of RDS for four to six hours. After infection, they cultured cells in the absence of RDS and then quantified the cells to determine if viral infection was inhibited at 48 and 72 hours.
Subsequently, the researchers used the Biomedical Research Lab on Mason’s Science and Technology Campus to confirm the in vitro efficacy of RDS against infectious SARS-CoV-2 virus.
The study revealed that RDS contains very potent ingredients that can destroy the infectivity of SARS-CoV, SARS-CoV-2, and influenza A virus, even at very low dosages, said Wu, a professor in Mason’s National Center for Biodefense and Infectious Diseases and a study co-author. In addition, the investigators have demonstrated that RDS is effective against the SARS-CoV-2 variants in vitro.
Hetrick, a Ph.D. student in biosciences working on the study, said that the discovery was a happy surprise for him. It would be great if there are safe and effective herbal drugs available for the management of COVID-19 in the future.
Hakami is currently conducting in vivo animal studies to build on the in vitro discovery that RDS may be used as a SARS-CoV-2 treatment. He is testing RDS using K18-hACE2 transgenic mice that will be infected with SARS-CoV-2. Depending on the results, Dejia Harmony, the sponsor of the above pre-clinical trial, may seek FDA approval to begin human clinical trials.
“This study points to the possibility of using a readily available, over-the-counter herbal beverage to provide protection against SARS-CoV-2 and influenza A infections,” said Ali Andalibi, senior associate dean in Mason’s College of Science. “It will also be quite interesting to see if RDS shows activity against other respiratory viruses.”
From the perspective of traditional Chinese medicine (TCM), COVID-19 can be considered a “plague.” TCM has played an essential role in prevention and control of plagues in China. Throughout the history of combating plagues, TCM has gradually forged a unique and complete system with invaluable experience in both theoretical and practical levels of treatment.
In recent history, TCM has provided alternative treatments for the effective prevention and control of novel acute respiratory tract infections around the world [7], [8]. Presently, the integration of TCM and allopathic medicine has formed the dominant treatment strategy in all COVID-19-affected areas across China [9].
The Lung-toxin Dispelling Formula No. 1 (祛肺毒一号方), referred to as Respiratory Detox Shot (RDS), is based on the theory of TCM medicinal properties, the classical prescription of TCM and clinical practice.
There are nine TCM ingredients in RDS:
- Schizonepetae Herba (Jingjie),
- Lonicerae Japonicae Flos (Jinyinhua),
- Forsythiae Fructus (Lianqiao),
- Scrophulariae Radix (Xuanshen),
- Gleditsiae Spina (Zaojiaoci),
- Armeniacae Semen Amarum (Kuxingren),
- Nidus Vespae (Fengfang),
- Glycyrrhizae Radix et Rhizoma (Gancao),
- Ginseng Radix et Rhizoma (Renshen).
The nine TCM ingredients in this prescription have been used together as an herbal formula in clinical practice for more than a decade and have been effective for the prevention and treatment of acute respiratory tract infections, as well as the common cold and flu.
In recent months, clinical trials of RDS have been conducted to evaluate its efficacy in patients with severe/critical COVID-19 pneumonia, finding that RDS has treatment value and no observed side effects [10]. Additionally, eight out of the nine ingredients in RDS are plant-derived; the other ingredient is honeycomb.
All nine ingredients are approved as dietary supplements by the United States Food and Drug Administration, indicating that their long-term use is considered to be safe in the US. RDS has therapeutic benefits in both disease prevention and treatment against COVID-19; these benefits may have global significance [10].
TCM has substantial advantages in treating complicated and severe diseases and has strong clinical support, but it is still considered as an alternative or complementary medicine, mainly because of that the specific biochemically active constituents of its prescriptions or their mechanisms of action are not identified.
The critical problem of the COVID-19 pandemic demands novel strategies that reach beyond conventional antiviral treatments [8], [11], [12], [13]. To better understand and promote the clinical use of RDS globally, this study investigates important biochemical constituents present in the formula and the biological processes that they may effect, eliciting the therapeutic effects of RDS.
Even though technological limitations in drug research have been reduced over time, challenges still exist in studying the biochemically active constituents present in TCM prescriptions and their mechanisms of action. TCM prescriptions present a complex chemical system, comprised of multiple TCM herbs.
The complex nature of TCM makes it difficult to study the action of the full prescription through the reductionist approach taken in contemporary medical research, which would recommend separating out individual herbal ingredients and potential targets in the investigation process [14], [15].
In the era of -omics technologies, a vast amount of data have become available and in some avenues of research, the focus has shifted emphasis from the classic “drug-reductionist” to the novel “drug-holistic” system-based approaches [16]. Network pharmacology is a branch of systems biology, which explores the correlation between drugs and diseases from a comprehensive perspective; this is consistent with the holistic view, systematic approach and compatibility principle of TCM [17], [18], [19].
The structure of 3-chymotrypsin-like protease (3CLpro) was determined after the emergence of severe acute respiratory syndrome (SARS) [20], [21]. It is the main protease that cleaves host polyproteins into viral replication-related proteins, and is highly conserved across the coronavirus family, including SARS coronavirus 2 (SARS-CoV-2), SARS coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus [22].
Therefore, it is an important target for the design of potential anti-coronavirus inhibitors [23]. One efficient approach used to screen potential active compounds against specific target proteins, such as 3CLpro, is molecular docking simulation [22], [23], [24], [25]. It is a universal and efficient approach in modern drug design and drug discovery.
The present study is designed based on the success of network analysis. A network of interactions among each TCM in the RDS formula, their meridian tropism, chemical composition and potential target proteins was established to investigate the possible pathways of action. This approach helps to predict the biochemically active constituents of this TCM prescription; it also provides a way to develop an in-depth understanding of how a complex drug system works to treat a complex disease. It is an important research strategy to understand the possible intervention mechanism of RDS on COVID-19 from the perspective of the biological and molecular networks.
This knowledge could help to develop an early prevention and treatment scheme to manage COVID-19 pneumonia. In this study, the ability of the active constituents of RDS to bind with SARS-CoV-2 3CLpro (6LU7) was evaluated using computational pattern recognition to test the likelihood of molecular docking. Finally, the chemical constituents present in RDS were tested against the putative biochemically active constituents identified in this study using ultrahigh-performance liquid chromatography (UPLC), coupled with tandem mass spectrometry in data-independent analysis mode (MSE) with non-targeted and targeted approaches. Through the above studies, biochemically active constituents from the RDS formula and their likely pathways of action were identified.
reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195604/
More information: Brian Hetrick et al, A traditional medicine, respiratory detox shot (RDS), inhibits the infection of SARS-CoV, SARS-CoV-2, and the influenza A virus in vitro, Cell & Bioscience (2021). DOI: 10.1186/s13578-021-00609-1
