자유게시판-한의약융합연구정보센터

코로나19가 2년 넘게 지속되면서 한의계에서도 전 세계적인 재난을 하루빨리 종식하고자 치료는 물론 예방 및 후유증 관리를 위해 지속적인 연구를 해오고 있습니다. KMCRIC에서는 코로나19 한의 임상연구를 모아 소개합니다.

■ KMCRIC 근거중심한의약 DB

2022년 3월 현재, 근거중심한의약 DB에서는 'COVID', 'Corona', 'Coronavirus', 'SARS', 'Pandemics' 등의 키워드로 검색 시 200여 건의 논문 검색 결과를 얻으실 수 있습니다. 그중 코로나19 한의 치료 및 한양방 병용 치료 효과에 대한 근거가 될 만한 논문을 선별했습니다. 연구자, 임상의분들에게 도움이 되고자 전문가의 한글 요약 및 비평을 소개합니다.

코로나 치료에 한약과 양약의 병용 투여는 효과적인가?

경희대학교 한의과대학 한방폐계내과학교실 이범준

https://www.kmcric.com/database/ebm_result_detail?cat=SR&access=S202107112

코로나19로 호흡기 감염이 무서운 요즘, 한약으로 감기를 예방할 수 있을까?

경희대학교한방병원 폐장호흡내과 김관일

https://www.kmcric.com/database/ebm_result_detail?cat=RCT&access=R202105001

코로나19 환자에게 식이 보충제 및 한약의 복용 효과는?

채영한의원 한은경

https://www.kmcric.com/database/ebm_result_detail?cat=SR&access=S202108102

연화청온(連花淸瘟)이 코로나19 치료에 효과적이고 안전한가?

경희대학교한방병원 폐장호흡내과 김관일

https://www.kmcric.com/database/ebm_result_detail?cat=SR&access=S202103001

경증, 중등증 코로나19에 연화청온(連花淸瘟)은 안전하고 효과적일까?

부산대학교 한의학전문대학원 최준용

https://www.kmcric.com/database/ebm_result_detail?cat=SR&access=S202105064

한약은 코로나19 치료에 효과적인가?

대구한의대학교 부속 포항한방병원 한방내과 최해윤

https://www.kmcric.com/database/ebm_result_detail?cat=SR&access=S202010001

코로나19 치료에 한양방 병행 요법이 효과적인가?

경희대학교한방병원 폐장호흡내과 김관일

https://www.kmcric.com/database/ebm_result_detail?cat=SR&access=S202008003

코로나19에 연화청온(連花淸瘟) 캡슐의 부가적 효과 - 2주 만에 대상자 모집이 끝난 대규모 다기관 무작위 연구

부산대학교한방병원 한의약임상연구센터 최준용

https://www.kmcric.com/database/ebm_result_detail?cat=RCT&access=R202005045

■ 코로나19 한의 기초연구

석산(꽃무릇) 추출물 라이코린( Lycorine) , 항코로나바이러스 효능 확인

Jin YH, Min JS, Jeon S, Lee J, Kim S, Park T, Park D, Jang MS, Park CM, Song JH, Kim HR, Kwon S. Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections. Phytomedicine. 2021 Jun;86:153440. doi: 10.1016/j.phymed.2020.153440. Epub 2020 Dec 16.

https://pubmed.ncbi.nlm.nih.gov/33376043/

Abstract

Background: Highly effective novel treatments need to be developed to suppress emerging coronavirus (CoV) infections such as COVID-19. The RNA dependent RNA polymerase (RdRp) among the viral proteins is known as an effective antiviral target. Lycorine is a phenanthridine Amaryllidaceae alkaloid isolated from the bulbs of Lycoris radiata (L'Hér.) Herb. and has various pharmacological bioactivities including antiviral function.

Purpose: We investigated the direct-inhibiting action of lycorine on CoV's RdRp, as potential treatment for emerging CoV infections.

Methods: We examined the inhibitory effect of lycorine on MERS-CoV, SARS-CoV, and SARS-CoV-2 infections, and then quantitatively measured the inhibitory effect of lycorine on MERS-CoV RdRp activity using a cell-based reporter assay. Finally, we performed the docking simulation with lycorine and SARS-CoV-2 RdRp.

Results: Lycorine efficiently inhibited these CoVs with IC50 values of 2.123 ± 0.053, 1.021 ± 0.025, and 0.878 ± 0.022 μM, respectively, comparable with anti-CoV effects of remdesivir. Lycorine directly inhibited MERS-CoV RdRp activity with an IC50 of 1.406 ± 0.260 μM, compared with remdesivir's IC50 value of 6.335 ± 0.731 μM. In addition, docking simulation showed that lycorine interacts with SARS-CoV-2 RdRp at the Asp623, Asn691, and Ser759 residues through hydrogen bonding, at which the binding affinities of lycorine (-6.2 kcal/mol) were higher than those of remdesivir (-4.7 kcal/mol).

Conclusions: Lycorine is a potent non-nucleoside direct-acting antiviral against emerging coronavirus infections and acts by inhibiting viral RdRp activity; therefore, lycorine may be a candidate against the current COVID-19 pandemic.

Keywords: COVID-19; Lycorine; RNA-dependent RNA polymerase; cell-based reporter assay; coronavirus; remdesivir.

개암풀 열매인 파고지(破故紙, psoralea corylifolia)의 면역증강 효능 기전 규명

Jin YH, Kim DE, Jang MS, Min JS, Kwon S. Bavachin produces immunoadjuvant activity by targeting the NFAT signaling pathway. Phytomedicine. 2021 Dec;93:153796. doi: 10.1016/j.phymed.2021.153796. Epub 2021 Oct 9. PMID: 34689117.

https://pubmed.ncbi.nlm.nih.gov/34689117/

Abstract

Background: Bavachin, a flavonoid compound isolated from the seeds and fruits of Psoralea corylifolia l. (family Fabaceae), is used as a traditional medicine in Asia. Indeed, it is reported to have various medicinal functions such as estrogenic and antiinflammatory activities among others. However, to date, the effects of bavachin on T cell activation have yet to be reported.

Purpose and study design: We aimed to determine the effects of bavachin on the activation of a human T cell line in vitro and on antigen-specific immune responses in mice in vivo.

Methods: In a nuclear factor of activated T cells (NFAT) activity assay, the Jurkat T cell line expressing a luciferase reporter driven by an NFAT-response element was stimulated with antihuman CD3/CD28 antibody and bavachin. Furthermore, the level of cytokine production was measured in the Jurkat T cell line stimulated with phorbol 12-myristate 13-acetate/ionomycin and bavachin using an IL-2 ELISA and a cytometric bead array assay. For in vivo analyses, mice were subcutaneously immunized with an antigen (ovalbumin protein) and bavachin, and the immune responses of mice were analyzed by FACS analysis, a T cell proliferation assay, a cytokine ELISA, and an antiovalbumin-specific antibody ELISA.

Results: We found that bavachin activated NFAT-mediated transcription in the human T cell line in vitro. In mice, when bavachin was administered with the antigen, an increase in T cell responses and antibody production specific to the antigen was observed.

Conclusion: Our results suggest that bavachin has immunoadjuvant and immunomodulation effects, which arise through activation of the NFAT signaling pathway.

Keywords: Jurkat cells; bavachin; immunoadjuvant; immunomodulation; nuclear factor of activated T cells; ovalbumin.

두꺼비의 피부와 귀밑 샘에서 분비되는 불투명한 흰색의 끈적한 독으로 알려진 섬수(蟾酥) 유래 물질의 강력한 항바이러스 효과 규명

Jin YH, Jeon S, Lee J, Kim S, Jang MS, Park CM, Song JH, Kim HR, Kwon S. Broad Spectrum Antiviral Properties of Cardiotonic Steroids Used as Potential Therapeutics for Emerging Coronavirus Infections. Pharmaceutics. 2021 Nov 2;13(11):1839. doi: 10.3390/pharmaceutics13111839. PMID: 34834252

https://pubmed.ncbi.nlm.nih.gov/34834252/

Abstract

Cardiotonic steroids are steroid-like natural compounds known to inhibit Na+/K+-ATPase pumps. To develop a broad-spectrum antiviral drug against the emerging coronavirus infection, this study assessed the antiviral properties of these compounds. The activity of seven types of cardiotonic steroids against the MERS-CoV, SARS-CoV, and SARS-CoV-2 coronavirus varieties was analyzed using immunofluorescence antiviral assay in virus-infected cells. Bufalin, cinobufagin, and telocinobufagin showed high anti-MERS-CoV activities (IC50, 0.017~0.027 μM); bufalin showed the most potent anti-SARS-CoV and SARS-CoV-2 activity (IC50, 0.016~0.019 μM); cinobufotalin and resibufogenin showed comparatively low anti-coronavirus activity (IC50, 0.231~1.612 μM). Differentially expressed genes in Calu3 cells treated with cinobufagin, telocinobufagin, or bufalin, which had high antiviral activity during MERS-CoV infection were analyzed using QuantSeq 3' mRNA-Seq analysis and data showed similar gene expression patterns. Furthermore, the intraperitoneal administration of 10 mg/kg/day bufalin, cinobufagin, or digitoxin induced 100% death after 1, 2, and 4 days in 5-day repeated dose toxicity studies and it indicated that bufalin had the strongest toxicity. Pharmacokinetic studies suggested that telocinobufagin, which had high anti-coronavirus activity and low toxicity, had better microsomal stability, lower CYP inhibition, and better oral bioavailability than cinobufagin. Therefore, telocinobufagin might be the most promising cardiotonic steroid as a therapeutic for emerging coronavirus infections, including COVID-19.

Keywords: COVID-19; MERS; antiviral; cardiotonic steroid; coronavirus; pharmacokinetics.

Kim DE, Min JS, Jang MS, Lee JY, Shin YS, Song JH, Kim HR, Kim S, Jin YH, Kwon S. Natural Bis-Benzylisoquinoline Alkaloids-Tetrandrine, Fangchinoline, and Cepharanthine, Inhibit Human Coronavirus OC43 Infection of MRC-5 Human Lung Cells. Biomolecules. 2019 Nov 4;9(11):696. doi: 10.3390/biom9110696. PMID: 31690059; PMCID: PMC6921063.

https://pubmed.ncbi.nlm.nih.gov/31690059/

Abstract

Stephania tetrandra and other related species of Menispermaceae are the major sources of the bis-benzylisoquinoline alkaloids tetrandrine (TET), fangchinoline (FAN), and cepharanthine (CEP). Although the pharmacological properties of these compounds include anticancer and anti-inflammatory activities, the antiviral effects of these compounds against human coronavirus (HCoV) remain unclear. Hence, the aims of the current study were to assess the antiviral activities of TET, FAN, and CEP and to elucidate the underlying mechanisms in HCoV-OC43-infected MRC-5 human lung cells. These compounds significantly inhibited virus-induced cell death at the early stage of virus infection. TET, FAN, and CEP treatment dramatically suppressed the replication of HCoV-OC43 as well as inhibited viral S and N protein expression. The virus-induced host response was reduced by compound treatment as compared with the vehicle control. Taken together, these findings demonstrate that TET, FAN, and CEP are potential natural antiviral agents for the prevention and treatment of HCoV-OC43 infection.

Keywords: MRC-5 human lung cell; antiviral effect; bis-benzylisoquinoline alkaloids; cepharanthine; fangchinoline; human coronavirus strain OC43; tetrandrine.

Min JS, Kim DE, Jin YH, Kwon S. Kurarinone Inhibits HCoV-OC43 Infection by Impairing the Virus-Induced Autophagic Flux in MRC-5 Human Lung Cells. J Clin Med. 2020 Jul 14;9(7):2230. doi: 10.3390/jcm9072230. PMID: 32674356; PMCID: PMC7408680.

https://pubmed.ncbi.nlm.nih.gov/32674356/

Abstract

Kurarinone is a prenylated flavonone isolated from the roots of Sophora flavescens. Among its known functions, kurarinone has both anti-apoptotic and anti-inflammatory properties. Coronaviruses (CoVs), including HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2, are the causative agents of respiratory virus infections that range in severity from the common cold to severe pneumonia. There are currently no effective treatments for coronavirus-associated diseases. In this report, we examined the anti-viral impact of kurarinone against infection with the human coronavirus, HCoV-OC43. We found that kurarinone inhibited HCoV-OC43 infection in human lung fibroblast MRC-5 cells in a dose-dependent manner with an IC50 of 3.458 ± 0.101 μM. Kurarinone inhibited the virus-induced cytopathic effect, as well as extracellular and intracellular viral RNA and viral protein expression. Time-of-addition experiments suggested that kurarinone acted at an early stage of virus infection. Finally, we found that HCoV-OC43 infection increased the autophagic flux in MRC-5 cells; kurarinone inhibited viral replication via its capacity to impair the virus-induced autophagic flux. As such, we suggest that kurarinone may be a useful therapeutic for the treatment of diseases associated with coronavirus infection.

Keywords: HCoV-OC43; LC3; MRC-5 cell; autophagy; coronavirus; infection; kurarinone; p62/SQSTM1 protein.

■ Integrative Medicine Research(IMR) 코로나19 한의 임상연구

코로나19에 대한 전통, 보완, 통합의학 기반 중재의 무작위배정 비교임상연구: 서지학적 분석 및 연구설계 고찰

Ang L, Song E, Lee MS. Randomized controlled trials of traditional, complementary, and integrative medicine-based interventions for coronavirus disease 2019 (COVID-19): A bibliometric analysis and review of study designs. Integr Med Res. 2021;10(Suppl):100777. doi: 10.1016/j.imr.2021.100777. Epub 2021 Sep 23.

https://pubmed.ncbi.nlm.nih.gov/34580628/

https://www.sciencedirect.com/science/article/pii/S2213422021000640?via%3Dihub

Infographics

Abstract

Background: To date, the coronavirus disease 2019 (COVID-19) pandemic remains ongoing and continues to affect millions of people worldwide. In the effort of fighting this pandemic, there has been an increasing interest in the potential of traditional, complementary, and integrative medicines (TCIMs) in engaging COVID-19. This study presents a bibliometric analysis of the research trends of TCIMs for COVID-19.

Methods: Six databases were searched on July 15, 2021, to retrieve all the citations on TCIM-focused randomized controlled trials (RCTs) available on COVID-19. Only RCTs that mentioned at least one TCIMs for the treatment and/or management or COVID-19 were eligible. Data such as number and countries of trials conducted, publication journal, research focus, study design, and sample size were extracted for analysis.

Results: The resulting 56 articles were authored by 553 unique authors, and included 28 English articles, 19 Chinese articles with English abstracts, and 9 Chinese articles without English abstract. Analyses had shown that China was the dominant country with TCIM related RCT publications, followed by India and the United States. The included articles were published across 24 English journals and 22 Chinese journals with a wide range of impact factors from 0.220 to 56.272. The most commonly studied TCIM modalities included Chinese herbal decoction (n=12) and Chinese patent medicine (n=16). In terms of study designs, TCIM interventions were integrated with standard medicine across the trials with most trials having a small to medium sample size and open-labeled.

Conclusion: This bibliometric analysis of RCTs demonstrated the research trends and characteristics of TCIM utilized in COVID-19 research. Although there are still many research gaps and limitations for pandemic research, the publication of TCIM-focused RCTs is anticipated to show a continuously increasing trend.

Keywords: Bibliometric; Clinical trials; Coronavirus; Pandemic; Research trends; Review; Study designs.

중증 코로나19로 입원한 환자의 폐 기능 및 호흡기 증상에 대한 기공 운동 및 지압 재활 프로그램의 효과: 무작위배정 비교임상연구

Liu ST, Zhan C, Ma YJ, Guo CY, Chen W, Fang XM, Fang L. Effect of qigong exercise and acupressure rehabilitation program on pulmonary function and respiratory symptoms in patients hospitalized with severe COVID-19: a randomized controlled trial. Integr Med Res. 2021;10(Suppl):100796. doi: 10.1016/j.imr.2021.100796. Epub 2021 Oct 29.

https://pubmed.ncbi.nlm.nih.gov/34733607/

https://www.sciencedirect.com/science/article/pii/S2213422021000834?via%3Dihub

Infographics

Abstract

Background: There are several effective complementary and integrative therapies for patients with severe COVID-19. The trial aims to evaluate the efficacy and advantages of the qigong exercise and acupressure rehabilitation program (QARP) for treating patients with severe COVID-19.

Methods: A total of 128 patients with COVID-19 aged 20 to 80 years were recruited and randomly allocated in a 1:1 ratio to receive QARP plus standard therapies or standard therapies alone. QARP consisted of acupressure therapy and qigong exercise (Liu Zi Jue). The primary outcome was measured with the modified Medical Research Council (mMRC) dyspnea scale, and the secondary outcomes included the modified Borg dyspnea scale (MBS), fatigue Scale-14 (FS-14), patient health questionnaire-9 scale (PHQ-9), duration of respiratory symptoms, and vital signs.

Results: In total, 128 patients completed the clinical trial. The QARP group and standard therapies group showed significant improvements in vital signs (except blood pressure) and clinical scales compared with baseline (p<0.05). The QARP group also showed more significant improvement in the mMRC dyspnea scale (-1.8 [-2.1, -1.6], p=0.018) and modified Borg dyspnea scale (-3.7 [95% confidence intervals (CI) -4.3, -3.1], p=0.045). The duration of cough was 14.3 days (95% CI 12.6, 16.1, p=0.046), and the length of hospital stay was 18.5 days (95% CI 17.0, 20.0, p=0.042) in the QARP group, both of which were significantly reduced compared with the standard therapies group (p<0.05).

Conclusion: QARP plus standard therapies improved lung function and symptoms such as dyspnea and cough in patients with severe COVID-19 and shortened the length of hospital stay. Therefore, QARP may be considered an effective treatment option for patients with severe COVID-19.

Trial registration: Clinical Research Information Service Identifier: ChiCTR2000029994.

Keywords: Acupressure; COVID-19; Pulmonary function; Qigong; Telerehabilitation.

■ 코로나19 한의 연구 뉴스기사

[중앙일보 2022-04-15]

코로나 완치됐는데 극심한 피로·무력감, 홍삼 꾸준히 섭취하면 개선 효과

https://news.koreadaily.com/2022/04/15/life/health/20220415141415881.html

[NATURE 2022-03-07]

코로나19 감염 후 뇌 영상 봤더니 후각·기억 영역 줄어

https://www.kmcric.com/news/newspaper/view/54320

[동아사이언스 2021-11-08]

부항·피지흡입기 원리로 세포막 열었더니 코로나 DNA 백신 효과100배

한미 공동연구, 사이언스 어드밴시스 발표