key: cord-0794961-qhxz3xj2 authors: Park, Sunju; Hahm, Dae-Hyun; Joo, Myungsoo; Kim, Kyongmin; Kwon, Sunoh; Choi, Hoyoung; Lee, Hyangsook title: The role of Korean Medicine in the post-COVID-19 era: an online panel discussion part 2 - basic research and education date: 2020-07-24 journal: Integr Med Res DOI: 10.1016/j.imr.2020.100488 sha: 0c3eee6f5eee06a6b56c5f6a528b4b18a57e807d doc_id: 794961 cord_uid: qhxz3xj2 Abstract Background Experiencing difficulties and challenges though COVID-19 pandemic, there are voices that it needs to be discussed to seek direction of basic research and college education of Korean Medicine (KM) so that KM community can play a significant role in the future infectious disease outbreaks. Methods This paper summarizes the edited highlights of an online video meeting by Google meet on May 19, 2020, organized by the Korean Medicine Convergence Research Information Center. Five researchers specialized in immunology, microbiology, virology, preventive medicine, and herbology, respectively, presented what KM community should prepare for the future acute infectious disease outbreaks by learning from the previous research on antiviral effect of herbs for coronavirus and the experiences of the present COVID-19 pandemic. Results There are a lot of herbs or natural products with potential anti-coronavirus effects reported from in vitro experiments and despite criticism, many clinical trials on traditional herbal medicine for COVID-19 are being conducted. In addition to establishing research evidence, KM community should train and produce public health professionals among Korean Medicine Doctors (KMDs) and official participation in public healthcare system should be ensured in terms of regulation and policy. Newly developed KM treatments can be interpreted by the KM theories and also should be allowed by regulations for KMDs to utilize them. Conclusion The present online discussion suggested directions of basic research for acute viral infections diseases utilizing KM and how to enforce relevant education and regulations in the post-COVID-19 era. . Table 1 . Information of speakers in the present discussion. Here is our data from an in vitro experiment. We created a cell culture, infected it with the virus, and found that Cimicifuga rhizoma, Meliae cortex, Coptidis rhizoma, and Phellodendron cortex inhibit replications of mouse hepatitis virus (MHV) and coronavirus 9 . We evaluated the virus titer wherein the baseline is 100, and a decrease below 10 is considered effective as an antiviral treatment. As you can see, Cimicifuga rhizoma, Meliae cortex, Coptidis rhizoma, and Phellodendron cortex showed values much lower than 10, demonstrating a marked inhibition of viral replication to the point where there was almost no RNA expression. Sophora subprostrata radix also had an antiviral effect (≤ 10, meaning that it was effective) and we assume that they inhibit RNA basically by inhibiting RNA polymerase, protease, or replication 9 . Our 2 nd paper was published in 2010. There, we reported on our in vitro experiments wherein Sophorae radix, Acanthopanacis cortex, Sanguisorbae radix, and Torilis fructus inhibited replication of the coronavirus. Ribavirin is a commonly used drug against RNA viruses. We observed that Sophorae radix, Acanthopanacis cortex, Sanguisorbae radix, and Torilis fructus markedly inhibited replication of the coronavirus as much as ribavirin. In the end, we completed the paper hypothesizing that while Sophorae radix, Acanthopanacis cortex, and Torilis fructus inhibit RNA dependent RNA polymerase replication, Sanguisorbae radix inhibits viral replication by inhibiting not RNA synthesis but later steps of the viral replication 10 . Stephania tetrandra is known for analgesic and anti-inflammatory effects in patients with arthritis and edema 11 . We could confirm the antiviral effect by concentration, using the cell-survival rates and the levels of viral M-protein RNA have decreased post-treatment of Stephania tetrandra. The release of inflammatory cytokines has also decreased post-treatment 12 . Researchers at the University of Wisconsin demonstrated in a translocation assay using a MERS pseudovirus 13 , dose-dependent inhibition of viral gene expression by tetrandrine and fangchinoline, which are the same compounds that our team used. These compounds are known as calcium channel blockers, and for the viral gene to be expressed, calcium channels must be working properly to allow Ca 2+ signaling. According to this study, treatment with these compounds reduced the signaling and, thus, inhibited viral gene expression. A trial of tetrandrine tablets which were used in our research, for COVID-19 treatment, is registered at ClinicalTrials.gov (https://www.clinicaltrials.gov/) and it focuses on reduction of inflammations, including pneumonia, due to the anti-inflammatory effect of tetrandrine, rather than the antiviral effect itself 14 . In contrast to the findings above, recently, articles criticizing that TCM products whose efficacy and safety have not been sufficiently verified, are being applied in clinical practice and even exported to Europe, were published in Nature (https://www.nature.com/articles/d41586-020-01284-x) and Science Hahm: Next, Prof. Park will discuss how KM can contribute to the public health system in the future via changes in university education and in legal and regulatory barriers. Park: Although the KM community has made significant progress by putting a lot of efforts in the current COVID-19 pandemic, compared to the past, I hope that we make more regular and systematic contributions to the public healthcare system in the future. David Quammen, the author of "Spillover: Animal Infections and the Next Human Pandemic," mentions 4 things that are essential to managing infectious diseases in the future: science, technology, public health, and politics 19 . I would also like to talk about the public health aspect. I have been thinking that not just the efforts of the KM community alone, but also the government and academia must collaborate, in a joint effort, towards establishing the basis and strengthening our capabilities. In the end, the goal is to develop the role of KM in managing infectious diseases and secure our expertise so that the KM community can play an active role in the infectious disease management. J o u r n a l P r e -p r o o f I have divided this presentation into three parts, i.e., establishing research evidence, education, and regulations (Fig. 3) . As research directions were already addressed, I would just add to that; there were cases in which the KM community has contributed to emergency situations, as in a recent teleconsultation center 7 . Thinking back, we need to establish in advance a data collection/utilization system that works even in emergencies. If there is a system that is designed with an expert researcher participating from early on and evaluated post hoc for improvement, I think those data would be useful in the future. I will skip the part about claims and claims data utilization since it was explained well in the 1 st KMCRIC online panel discussion 2 . Others also addressed the role of infectious disease research and accumulating relevant knowledge. As the president Moon mentioned in his 3 rd inaugural anniversary speech establishing a national research center for infectious diseases, I hope that the KM community can take part in it as well. And lastly, we should continue to explore ways for the KM community to participate in public healthcare and think about our role in it. Next, in terms of education, students of colleges of KM are educated and trained in epidemiology and medical statistics, but they are not well-aware of their importance, and thus, engagement is rather limited. I think we should focus on education to emphasize the importance of these subjects and reinforce the utilization plan. Of course, they are already included in the curriculum and taught in colleges, but I think education, related to the public sector, must also be reinforced. Students should fully grasp the characteristics and role of public healthcare in their undergraduate studies, and their sense of commitment to society should be nurtured as well. Next, I think it is also essential to train KMD public health professionals and strengthen the competence and professionalize the KM community. In terms of upbringing KMD public health professionals, I hope that the number of professionals in preventive KM increases. Also, they should be allowed to work as epidemiological investigators by law, which I will mention again in part about KMDs serving the army in the public health centers. After all these things are achieved, they should be supplemented in terms of regulation and policy. The Infectious Disease Prevention Act and related laws should be enhanced, and, as the activities of epidemiological investigation teams increase, the application requirements should be modified so that KMDs can apply as well. Next, we should continue to establish measures to expand the participation of KMDs in public healthcare, such as increasing recruitment in national and public hospitals, health J o u r n a l P r e -p r o o f centers and the task force on infectious diseases. Finally, I think the plan should be expanded to include KMDs in specialized educational institutions and create a curriculum for training public health professionals to strengthen their competences and achieve professionalization. should be part of their work as KMDs in the future so that they are motivated to study hard in colleges. They will study even harder at school and work harder after graduation if these topics are reflected in the national examination. If not, then I think students will not be as persistent or interested, even if the courses are provided. Research on herbal medicine treatment is accomplished by the various efforts of researchers, trained and working in the field of KM, so the findings must be applied in human health for sure, as well as KM clinical practice. Currently, however, various research findings cannot be used in KM clinical practice due to legal or regulatory barriers. For example, Shinbaro tablet (GCSB-5), which was developed by the Jaseng Hospital of KM, cannot be used by KMDs, and only WM doctors are allowed to use it. While it is beneficial for human health, the KM community is facing many difficulties, as the results of KM community's hard work and large investment are not permitted to be applied to the field of KM. For the COVID-19, it is a crucial factor whether KMDs can use research findings in their practice to treat various symptoms of the COVID-19. Therefore, research is essential, but I think legal and regulatory improvements are also necessary. To conclude, we need to reinforce education and courses on infectious diseases, and I think, linking it to the work of KMDs will be quite crucial. I think we should create a system in which KMDs can participate in the treatment of infectious diseases. In terms of research, we should advise on developing herbal medicine treatment for infectious diseases that can be used by the KMDs via legal and regulatory improvements. Hahm: Thank you. Prof. Hoyoung Choi gave us a full lecture on herbal medicine and things to be supplemented, and he explained that education and research must be expanded to cover infectious diseases, but definitely there are regulatory barriers to be improved. I thank all the panel members who presented earlier. Lee: Thank you so much for sharing your valuable experiences and opinions. There were many good comments, and no one expects the answers to be found in this one encounter. The world is rapidly J o u r n a l P r e -p r o o f changing amidst many other problems and I think the most critical task is to establish the basis so that we can argue for the role of KM in academics and clinical practice, and of KMDs as healthcare professionals. And as prof. Hahm said, such a task should begin with education. I also believe that although the work in each field is different, the evidence from each area will eventually accumulate to establish the supporting background. There should still be many more discussions in each field, and I hope that even more sound evidence be established through our efforts. Thank you. This work did not require an ethical approval as it does not involve any human or animal experiment. The full recording of this online panel discussion can be accessed at https://www.kmcric.com/education/speciallecture/view_seminar/42922. SARS: epidemiology Worldwide reduction in MERS cases and deaths since Global Covid-19 Case Fatality Rates Confirmation of effectiveness of non face-to-face treatment via Korean Medicine teleconsultation center Naming the coronavirus disease (COVID-19) and the virus that causes it In vitro inhibition of coronavirus replications by the traditionally used medicinal herbal extracts, Cimicifuga rhizoma, Meliae cortex, Coptidis rhizoma, and Phellodendron cortex Medicinal herbal extracts of Sophorae radix, Acanthopanacis cortex, Sanguisorbae radix and Torilis fructus inhibit coronavirus replication in vitro Suppressive effects of Stephania tetrandra on the neutrophil function in patients with rheumatoid arthritis Inhibit Human Coronavirus OC43 Infection of MRC-5 Human Lung Cells NAADP-dependent Ca China is promoting coronavirus treatments based on unproven traditional medicines Unproven herbal remedy against COVID-19 could fuel drug-resistant malaria, scientists warn. Science News May 6 th Evidence exists" -does traditional medicine work for COVID-19? More Chinese Traditional Medicine, Unfortunately. In the pipeline: Science Translational Medicine Animal Infections and the Next Human Pandemic Can Chinese Medicine Be Used for Prevention of Corona Virus Disease 2019 (COVID-19)? A Review of Historical Classics, Research Evidence and Current Prevention Programs Korean Medicine Clinical Practice Guideline for COVID-19 Korean Herbal Pharmacopoeia Shanghai: Shanghai Science and Technology Press The authors thank Dr. Jeeyoung Shin, Ms. Eunji Kim, and Ms. Jooyoung Jo for their administrative work for the online panel discussion event. We also appreciate Drs. Gunwoong Kim and Gajin Han for transcription and proofreading of the manuscript. The authors declare that they have no competing interests.