Journal of Microbiology

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Inhibiting kinesin family member 20A disrupts Zika virus entry by blocking internalization: Jeonghyeon Lee, Younghyun Lim, Hyeong-Rae Kim, Yong-Bin Cho, In-Gu Lee, Young-Jin Seo; J. Microbiol. 2025;63(6):e2503008. Published online June 30, 2025; DOI: https://doi.org/10.71150/jm.2503008

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Abstract PDF Supplementary Material: Zika virus, a mosquito-borne virus, is associated with congenital birth defects and neurological complications. However, despite its significant public health threat, no approved vaccines or antiviral treatments are currently available. Therefore, this study aims to identify kinesin family member 20A as a key host factor promoting Zika virus life cycle. The elevated expression of kinesin family member 20A following Zika virus infection suggests its role in the viral life cycle. Suppressing its expression through gene silencing or inhibiting its function with a small-molecule inhibitor significantly reduced viral infectivity in host cells. Furthermore, kinesin family member 20A is essential for facilitating viral internalization, a key step in the entry step. These findings suggest its significance in the Zika virus life cycle and highlight its potential as a novel therapeutic target for the Zika virus.

Antiviral effects of heme oxygenase-1 against canine coronavirus and canine influenza virus in vitro: Jae-Hyeong Kim, Dong-Hwi Kim, Kyu-Beom Lim, Joong-Bok Lee, Seung-Yong Park, Chang-Seon Song, Sang-Won Lee, Dong-Hun Lee, Do-Geun Kim, Hun-Young Yoon, In-Soo Choi; J. Microbiol. 2025;63(5):e2501029. Published online May 27, 2025; DOI: https://doi.org/10.71150/jm.2501029

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Abstract PDF Supplementary Material: Heme oxygenase-1 (HO-1) has antioxidant, anti-apoptotic, and anti-inflammatory properties. Emerging evidence shows that HO-1 also exhibits antiviral activity against severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus, hepatitis B virus, and Ebola virus. Its antiviral effects are mediated not only by its enzymatic function but also through the modulation of interferon-related pathways, thereby inhibiting viral replication. In this study, we investigated the antiviral effects of HO-1 on canine coronavirus (CCoV) and canine influenza virus (CIV) H3N2 using cell-based assays. To determine whether HO-1 suppresses CCoV and CIV, cells were treated with hemin to induce HO-1 expression. Hemin treatment successfully induced HO-1 expression in A72 and Madin-Darby canine kidney cells, resulting in the suppression of CCoV and CIV replication. The canine HO-1 gene was cloned into an expression vector and transfected into cells to achieve transient overexpression. Recombinant canine HO-1 protein was expressed in Escherichia coli and purified using an expression vector. HO-1 overexpression suppressed CCoV and CIV replication in cells. Following viral infection, treatment with purified HO-1 protein led to a reduction in viral protein levels. Therefore, both HO-1 expression and exogenous protein treatment effectively inhibited CCoV and CIV replication. Elevated HO-1 protein levels consistently reduced viral RNA and protein expression in vitro. These findings suggest that HO-1 could serve as a potential therapeutic agent for managing viral infections in dogs.

Review

The Role of Extracellular Vesicles in Pandemic Viral Infections: Woosung Shim, Anjae Lee, Jung-Hyun Lee; J. Microbiol. 2024;62(6):419-427. Published online June 25, 2024; DOI: https://doi.org/10.1007/s12275-024-00144-x

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Extracellular vesicles (EVs), of diverse origin and content, are membranous structures secreted by a broad range of cell types. Recent advances in molecular biology have highlighted the pivotal role of EVs in mediating intercellular communication, facilitated by their ability to transport a diverse range of biomolecules, including proteins, lipids, DNA, RNA and metabolites. A striking feature of EVs is their ability to exert dual effects during viral infections, involving both proviral and antiviral effects. This review explores the dual roles of EVs, particularly in the context of pandemic viruses such as HIV-1 and SARS-CoV-2. On the one hand, EVs can enhance viral replication and exacerbate pathogenesis by transferring viral components to susceptible cells. On the other hand, they have intrinsic antiviral properties, including activation of immune responses and direct inhibition of viral infection. By exploring these contrasting functions, our review emphasizes the complexity of EV-mediated interactions in viral pathogenesis and highlights their potential as targets for therapeutic intervention. The insights obtained from investigating EVs in the context of HIV-1 and SARS-CoV-2 provide a deeper understanding of viral mechanisms and pathologies, and offer a new perspective on managing and mitigating the impact of these global health challenges.

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Differential Impact of Spike Protein Mutations on SARS-CoV-2 Infectivity and Immune Evasion: Insights from Delta and Kappa Variants
Tae-Hun Kim, Sojung Bae, Jinjong Myoung
Journal of Microbiology and Biotechnology.2024; 34(12): 2506. CrossRef

Journal Articles

The Regulation of Phosphorus Release by Penicillium chrysogenum in Different Phosphate via the TCA Cycle and Mycelial Morphology: Liyan Wang , Da Tian , Xiaoru Zhang , Mingxue Han , Xiaohui Cheng , Xinxin Ye , Chaochun Zhang , Hongjian Gao , Zhen Li; J. Microbiol. 2023;61(8):765-775. Published online September 4, 2023; DOI: https://doi.org/10.1007/s12275-023-00072-2

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Phosphate-solubilizing fungi (PSF) efficiently dissolve insoluble phosphates through the production of organic acids. This study investigates the mechanisms of organic acid secretion by PSF, specifically Penicillium chrysogenum, under tricalcium phosphate ( Ca3(PO4)2, Ca–P) and ferric phosphate ( FePO4, Fe–P) conditions. Penicillium chrysogenum exhibited higher phosphorus (P) release efficiency from Ca-P (693.6 mg/L) than from Fe–P (162.6 mg/L). However, Fe–P significantly enhanced oxalic acid (1193.7 mg/L) and citric acid (227.7 mg/L) production by Penicillium chrysogenum compared with Ca–P (905.7 and 3.5 mg/L, respectively). The presence of Fe–P upregulated the expression of genes and activity of enzymes related to the tricarboxylic acid cycle, including pyruvate dehydrogenase and citrate synthase. Additionally, Fe–P upregulated the expression of chitinase and endoglucanase genes, inducing a transformation of Penicillium chrysogenum mycelial morphology from pellet to filamentous. The filamentous morphology exhibited higher efficiency in oxalic acid secretion and P release from Fe–P and Ca–P. Compared with pellet morphology, filamentous morphology enhanced P release capacity by > 40% and > 18% in Ca–P and Fe–P, respectively. This study explored the strategies employed by PSF to improve the dissolution of different insoluble phosphates.

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Mechanistic insights into the transcriptomic and metabolomic responses of Curcuma wenyujin under high phosphorus stress
Yu Liu, Chen Wang, Wenqing Xu, Ruike Fan, Zhigang Wu, Lishang Dai
BMC Plant Biology.2025;[Epub] CrossRef
Improving Organic Acid Secretion of Aspergillus niger by Overexpression C4-Dicarboxylic Acid Transporters
Yiyang Tan, Shutong Liu, Sheng Wu, Xiaolu Wang, Depei Wang, Xianli Xue
Fermentation.2025; 11(3): 156. CrossRef
Penicillium restrictum Reshapes Root Exudates and Inhibits Peucedanum praeruptorum Bolting Through Field Inoculation and Co‐Cultivation
Cheng Song, Haoyu Pan, Yuanyuan Wang, Ranran Liao, Muhammad Arif, Haiyu Wang, Shanyong Yi, Bangxing Han
Plant Pathology.2025; 74(7): 2035. CrossRef
Boosting plant welfare and rhizospheric health through the application of phosphorus and potassium-solubilizing fungi from compost and vermicompost
A.J. Toribio, F. Suárez-Estrella, M.M. Jurado, J.A. López-González, M.R. Martínez-Gallardo, M.J. Estrella-González, M.J. López
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Integrated Proteomic and Physiological Profiling of Phosphate Stress Response in Potato (Solanum tuberosum L.)
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Comparative study of the geographical spread of genogroup II porcine norovirus and human norovirus: Eung Seo Koo , Yong Seok Jeong; J. Microbiol. 2021;59(7):644-650. Published online July 1, 2021; DOI: https://doi.org/10.1007/s12275-021-1218-1

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Livestock pigs and porcine norovirus could be candidate tools for future studies on the geographic isolation of norovirus. In this study, we provide the first evidence for geographic isolation of the host as a determinant of the distribution of subgenotypes of the porcine norovirus genogroup II (GII) genotype 11. Environmental water samples were collected from peri-urban streams and estuaries in South Korea between 2014 and 2020. In total, 488 GII region C sequences of norovirus open reading frame 2 were isolated. A total of 14 genotypes were detected, two of which (GII.11 and GII.18) corresponded to porcine norovirus. Five human norovirus genotypes (GII.2, GII.3, GII.4, GII.6, and GII.17) and one porcine norovirus genotype (GII.11) comprised the subgenotypes. Integrated analysis of seasonal and geographical factors revealed that the possibility of the co-emergence of different GII.11 subgenotypes in the same province was lower than that of human norovirus subgenotypes in the same province. Additional algorithms designed to eliminate potential biases further supported the estimated restricted geographical spread of the GII.11 subgenotypes. Fecal contamination source tracking revealed low detection rates of porcine norovirus in the absence of upstream pig farms. These results suggest that a one-sided viral transmission route, mainly dependent on indirect contact owing to the limited chance of direct contact between geographically separated livestock pig populations, may be responsible for the restricted geographical spread of the GII.11 subgenotypes.

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Swine Norovirus: Past, Present, and Future
Lara Cavicchio, Andrea Laconi, Alessandra Piccirillo, Maria Serena Beato
Viruses.2022; 14(3): 537. CrossRef

Potency of Phlebia species of white rot fungi for the aerobic degradation, transformation and mineralization of lindane: Pengfei Xiao , Ryuichiro Kondo; J. Microbiol. 2020;58(5):395-404. Published online March 28, 2020; DOI: https://doi.org/10.1007/s12275-020-9492-x

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The widespread use of the organochlorine insecticide lindane in the world has caused serious environmental problems. The main purpose of this paper is to investigate the potency of several Phlebia species of white rot fungi to degrade, transform and mineralize lindane, and to provide the feasibility of using white rot fungi for bioremediation at contaminated sites. Based on tolerance experiment results, Phlebia brevispora and Phlebia lindtneri had the highest tolerance to lindane and were screened by degradation tests. After 25 days of incubation, P. brevispora and P. lindtneri degraded 87.2 and 73.3% of lindane in low nitrogen medium and 75.8 and 64.9% of lindane in high nitrogen medium, respectively. Several unreported hydroxylation metabolites, including monohydroxylated, dehydroxylated, and trihydroxylated products, were detected and identified by GC/MS as metabolites of lindane. More than 10% of [14C] lindane was mineralized to 14CO2 by two fungi after 60 days of incubation, and the mineralization was slightly promoted by the addition of glucose. Additionally, the degradation of lindane and the formation of metabolites were efficiently inhibited by piperonyl butoxide, demonstrating that cytochrome P450 enzymes are involved in the fungal transformation of lindane. The present study showed that P. brevispora and P. lindtneri were efficient degraders of lindane; hence, they can be applied in the bioremediation process of lindane-contaminated sites.

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Wenquan Zhang, Qiaoyu Li, Jianqiao Wang, Ziyu Wang, Hongjie Zhan, Xiaolong Yu, Yan Zheng, Tangfu Xiao, Li-Wei Zhou
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Anti-varicella-zoster virus activity of cephalotaxine esters in vitro: Jung-Eun Kim , Yoon-Jae Song; J. Microbiol. 2019;57(1):74-79. Published online November 19, 2018; DOI: https://doi.org/10.1007/s12275-019-8514-z

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Abstract PDF

Harringtonine (HT) and homoharringtonine (HHT), alkaloid esters isolated from the genus Cephalotaxus, exhibit antitumor activity. A semisynthetic HHT has been approved for treatment of chronic myelogenous leukemia. In addition to antileukemic activity, HT and HHT are reported to possess potent antiviral activity. In this study, we investigated the effects of HT and HHT on replication of varicella-zoster virus (VZV) in vitro. HT and HHT, but not their biologically inactive parental alkaloid cephalotaxine (CET), significantly inhibited replication of recombinant VZV-pOka luciferase. Furthermore, HT and HHT, but not CET, strongly induced down-regulation of VZV lytic genes and exerted potent antiviral effects against a VZV clinical isolate. The collective data support the utility of HT and HHT as effective antiviral candidates for treatment of VZV-associated diseases.

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Antiviral activity of Schizonepeta tenuifolia Briquet against noroviruses via induction of antiviral interferons: Yee Ching Ng , Ye Won Kim , Jeong-Su Lee , Sung Joon Lee , Moon Jung Song; J. Microbiol. 2018;56(9):683-689. Published online August 23, 2018; DOI: https://doi.org/10.1007/s12275-018-8228-7

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Abstract PDF

Human noroviruses are the causative agents of non-bacterial gastroenteritis worldwide. The rapid onset and resolution of disease symptoms suggest that innate immune responses are critical for controlling norovirus infection; however, no effective antivirals are yet available. The present study was conducted to examine the antiviral activities of Schizonepeta tenuifolia Briquet extract (STE) against noroviruses. Treatment of human norovirus replicon-bearing HG23 cells with STE at 5 and 10 mg/ml concentrations resulted in the reduction in the viral RNA levels by 77.2% and 85.9%, respectively. STE had no cytotoxic effects on HG23 cells. Treatment of RAW 264.7 cells infected with murine norovirus 1 (MNV-1), a surrogate virus of human noroviruses, with STE at 10 and 20 μg/ml concentrations resulted in the reduction of viral replication by 58.5% and 84.9%, respectively. STE treatment induced the expression of mRNAs for type I and type II interferons in HG23 cells and upregulated the transcription of interferon-β in infected RAW 264.7 cells via increased phosphorylation of interferon regulatory factor 3, a critical transcription regulator for type I interferon production. These
results
suggest that STE inhibits norovirus replication through the induction of antiviral interferon production during virus replication and may serve as a candidate antiviral substance for treatment against noroviruses.

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Antiviral activity of Poncirus trifoliata seed extract against oseltamivirresistant influenza virus: Yoonki Heo , Yeondong Cho , Kwon sung Ju , Hansam Cho , Ki Hoon Park , Hanul Choi , Jong Kwang Yoon , Chiung Moon , Young Bong Kim; J. Microbiol. 2018;56(8):586-592. Published online July 25, 2018; DOI: https://doi.org/10.1007/s12275-018-8222-0

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The emergence of oseltamivir-resistant variants of influenza virus has highlighted the necessity for the development of more effective novel antiviral drugs. To date, numerous researchers have focused on developing antiviral drugs using natural resources, such as traditional herbal medicines. Poncirus trifoliata is widely used in oriental medicine as a remedy for gastritis, dysentery, inflammation and digestive ulcers. In this study, we investigated the potential antiviral effect of the Poncirus trifoliata orange seed extract against influenza virus. An ethanol extract of Poncirus trifoliata seeds (PTex) inhibited the activity of influenza viruses, in particular, oseltamivir- resistant strains, in Madin-Darby canine kidney cells. In contrast to oseltamivir, PTex exerted a significant inhibitory effect on the cellular penetration pathway of the virus rather than HA receptor binding. The potent antiviral effect and novel working mechanism of PTex support its further development as an effective natural antiviral drug with a wide spectrum of activity against influenza and oseltamivir-resistant viruses.

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An ethanol extract of Lysimachia mauritiana exhibits inhibitory activity against hepatitis E virus genotype 3 replication: Seong Eun Jin , Jung-Eun Kim , Sun Yeou Kim , Bang Ju Park , Yoon-Jae Song; J. Microbiol. 2017;55(12):984-988. Published online December 7, 2017; DOI: https://doi.org/10.1007/s12275-017-7477-1

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Hepatitis E virus (HEV) is an etiological agent of acute hepatitis E, a self-limiting disease prevalent in developing countries. HEV can cause fulminant hepatic failure with high mortality rates in pregnant women, and genotype 3 is reported to trigger chronic hepatitis in immunocompromised individuals worldwide. Screening of plant extracts for compounds with potential anti-HEV effects led to the identification of a 70% ethanol extract of Lysimachia mauritiana (LME) that interferes with replication of the swine HEV genotype 3 replicon. Furthermore, LME significantly inhibited replication of HEV genotype 3 and expression of HEV ORF2 in infected cells without exerting cytotoxic effects. Collectively, our findings demonstrate the potential utility of LME in the development of novel antiviral drugs against HEV infection.

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Nicola Frericks, Mara Klöhn, Frauke Lange, Lilli Pottkämper, Arnaud Carpentier, Eike Steinmann
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Seedling Growth of Lysimachia mauritiana Lam. by Cell Size and Nutrient Solution Concentration
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Yoon-Young Sung, Seung-Hyung Kim, Won-Kyung Yang, Heung Joo Yuk, Mi-Sun Kim, Dong-Seon Kim
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Comparison of anti-influenza virus activity and pharmacokinetics of oseltamivir free base and oseltamivir phosphate: Jin Soo Shin , Keun Bon Ku , Yejin Jang , Yi-Seul Yoon , Daeho Shin , Oh Seung Kwon , Yun Young Go , Seong Soon Kim , Myoung Ae Bae , Meehyein Kim; J. Microbiol. 2017;55(12):979-983. Published online December 7, 2017; DOI: https://doi.org/10.1007/s12275-017-7371-x

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Abstract PDF

Influenza viruses are major human respiratory pathogens that cause high morbidity and mortality worldwide. Currently, prophylactic vaccines and therapeutic antiviral agents are used to prevent and control influenza virus infection. Oseltamivir free base (OSV-FB), a modified generic antiviral drug of Tamiflu (oseltamivir phosphate, OSV-P), was launched in the Republic of Korea last year. Here, we examine the bioequivalence of these two compounds by assessing their antiviral efficacy in infected cells and in a mouse model. It was observed that both antivirals showed comparable efficacy against 11 different influenza A and B viruses in vitro. Moreover, in mice infected with influenza A virus (mouse-adapted A/Puerto Rico/8/34), they showed a dose-dependent therapeutic activity and alleviated infection-mediated reductions in body weight, leading to significantly better survival. There was histopathological disappearance of virus-induced inflammatory cell infiltration of the lung after oral treatment with either antiviral agent (at 10 mg/kg). Pharmacokinetic analysis also exhibited similar plasma concentrations of the active drug, oseltamivir carboxylate, metabolised from both OSVB and OSV-P. This is the first report showing bioequivalence of OSV-FB to its phosphate salt form in the mouse system. The free base drug has some beneficial points including simple drug formulation process and reduced risk of undesirable cation-phosphate precipitation within solution. The long term stability of OSV-FB requires further monitoring when it is provided as a national stock in readiness for an influenza pandemic.

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Yejin Jang, Jin Soo Shin, Joo-Youn Lee, Heegwon Shin, Sang Jick Kim, Meehyein Kim
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Tran Minh Ngoc, Nguyen Thi Thanh Phuong, Nguyen Minh Khoi, SeonJu Park, Hee Jae Kwak, Nguyen Xuan Nhiem, Bui Thi Thu Trang, Bui Huu Tai, Jae-Hyoung Song, Hyun-Jeong Ko, Seung Hyun Kim
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Salinomycin Inhibits Influenza Virus Infection by Disrupting Endosomal Acidification and Viral Matrix Protein 2 Function
Yejin Jang, Jin Soo Shin, Yi-Seul Yoon, Yun Young Go, Hye Won Lee, Oh Seung Kwon, Sehee Park, Man-Seong Park, Meehyein Kim, Jae U. Jung
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The Cranberry Extract Oximacro® Exerts in vitro Virucidal Activity Against Influenza Virus by Interfering With Hemagglutinin
Anna Luganini, Maria E. Terlizzi, Gianluca Catucci, Gianfranco Gilardi, Massimo E. Maffei, Giorgio Gribaudo
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Dense Granule Protein-7 (GRA-7) of Toxoplasma gondii inhibits viral replication in vitro and in vivo: Prasanna Weeratunga , Thilina U. B. Herath , Tae-Hwan Kim , Hyun-Cheol Lee , Jae-Hoon Kim , Byeong-Hoon Lee , Eun-Seo Lee , Kiramage Chathuranga , W. A. Gayan Chathuranga , Chul-Su Yang , Jin Yeul Ma , Jong-Soo Lee; J. Microbiol. 2017;55(11):909-917. Published online October 27, 2017; DOI: https://doi.org/10.1007/s12275-017-7392-5

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Dense granule protein-7 (GRA-7) is an excretory protein of Toxoplasma gondii. It is a potential serodiagnostic marker and vaccine candidate for toxoplasmosis. Previous reports demonstrated that GRA-7 induces innate immune responses in macrophages by interacting with TRAF6 via the MyD88- dependent pathway. In the present study, we evaluated the antiviral activity and induction of an antiviral state by GRA-7 both in vitro and in vivo. It was observed that GRA-7 markedly reduced the replication of vesicular stomatitis virus (VSVGFP), influenza A virus (PR8-GFP), coxsackievirus (H3- GFP), herpes simplex virus (HSV-GFP), and adenovirus-GFP in epithelial (HEK293T/HeLa) and immune (RAW264.7) cells. These antiviral activities of GRA-7 were attributed to the induction of type I interferon (IFN) signaling, resulting in the secretion of IFNs and pro-inflammatory cytokines. Additionally, in BALB/c mice, intranasal administration of GRA-7 prevented lethal infection by influenza A virus (H1N1) and exhibited prophylactic effects against respiratory syncytial virus (RSV-GFP). Collectively, these results suggested that GRA-7 exhibits immunostimulatory and broad spectrum antiviral activities via type I IFN signaling. Thus, GRA-7 can be potentially used as a vaccine adjuvant or as a candidate drug with prophylactic potential against viruses.

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Marwa A. Gouda, Hind S. AboShabaan, Ahmed S. Abdelgawad, Aliaa Sabry Abdel Wahed, Khaled A. Abd El-Razik, Yara Elsaadawy, Ayman. A. Abdel-Wahab, Yousry Hawash
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Kevin Roe
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Yuanxi Shen, Zhaozhe Wang, Jiajing Li, Rui Xu, Rongyi Ji, Jiaojiao Lin, Chuangang Zhu
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Coptidis Rhizoma extract inhibits replication of respiratory syncytial virus in vitro and in vivo by inducing antiviral state: Byeong-Hoon Lee , Kiramage Chathuranga , Md Bashir Uddin , Prasanna Weeratunga , Myun Soo Kim , Won-Kyung Cho , Hong Ik Kim , Jin Yeul Ma , Jong-Soo Lee; J. Microbiol. 2017;55(6):488-498. Published online May 28, 2017; DOI: https://doi.org/10.1007/s12275-017-7088-x

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Coptidis Rhizoma is derived from the dried rhizome of Ranun-culaceous plants and is a commonly used traditional Chinese medicine. Although Coptidis Rhizoma is commonly used for its many therapeutic effects, antiviral activity against respi-ratory syncytial virus (RSV) has not been reported in detail. In this study, we evaluated the antiviral activities of Coptidis Rhizoma extract (CRE) against RSV in human respiratory tract cell line (HEp2) and BALB/c mice. An effective dose of CRE significantly reduces the replication of RSV in HEp2 cells and reduces the RSV-induced cell death. This antiviral activity against RSV was through the induction of type I inter-feron-related signaling and the antiviral state in HEp2 cells. More importantly, oral administration of CRE exhibited prophylactic effects in BALB/c mice against RSV. In HPLC analysis, we found the presence of several compounds in the aqueous fraction and among them; we confirmed that pal-matine was related to the antiviral properties and immune- modulation effect. Taken together, an extract of Coptidis Rhi-zoma and its components play roles as immunomodulators and could be a potential source as promising natural antivirals that can confer protection to RSV. These outcomes should encourage further allied studies in other natural products.

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Review

REVIEW] Hemorrhagic fever of bunyavirus etiology: disease models and progress towards new therapies: Brian B. Gowen , Brady T. Hickerson; J. Microbiol. 2017;55(3):183-195. Published online February 28, 2017; DOI: https://doi.org/10.1007/s12275-017-7029-8

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Abstract PDF

A growing number of bunyaviruses are known to cause viral hemorrhagic fever (VHF), a severe febrile illness which can progress to hypovolemic shock and multi-organ failure and is characterized by hematologic abnormalities and vascular leak. At present, there are no approved vaccines or antiviral therapies to effectively prevent or treat VHF caused by pathogenic bunyaviruses. Advances in the modeling of bunyaviral infections have facilitated efforts towards the development of novel post-exposure prophylactic and therapeutic countermeasures, several of which may some day be approved for human use. Here, we review recent progress in animal models of severe bunyaviral infections essential to this mission, as well as promising antivirals and biologicals that are at various stages of the development process.

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Journal Article

MDA7/IL-24 is an anti-viral factor that inhibits influenza virus replication: Rak-Kyun Seong , Young-Ki Choi , Ok Sarah Shin; J. Microbiol. 2016;54(10):695-700. Published online September 30, 2016; DOI: https://doi.org/10.1007/s12275-016-6383-2

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Abstract PDF

Melanoma differentiation associated gene-7 (mda-7)/interleukin- 24 (IL-24) is a secreted cytokine, which plays an essential role in tumor suppression. Although its role as a multifunctional protein affecting broad types of cancers is well described, functions of IL-24 in host defense against virus infection are yet to be determined. In this study, we explored the anti-viral effect of recombinant IL-24 treatment during influenza infection. Infection of human lung adenocarcinoma cells (A549) with the influenza A virus up-regulated IL-24 mRNA and protein expression in a time-dependent manner. Pre-treatment of A549 cells with recombinant IL-24 protein effectively suppressed viral plaque formation. Furthermore, IL-24 treatment of A549 cells reduced viral non-structural protein 1 (NS1) synthesis, whereas IL-24 knockdown resulted in increased viral replication. Interestingly, IL-24 treatment following influenza A virus infection led to up-regulation of interferon (IFN)-induced antiviral signaling. Taken together, our results suggest that IL-24 exerts a potent suppressive effect on influenza viral replication and can be used in the treatment of influenza infection.

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Review

MINIREVIEW] Multilayered regulations of RIG-I in the anti-viral signaling pathway: Nari Kim , Hesung Now , Nhung T.H. Nguyen , Joo-Yeon Yoo; J. Microbiol. 2016;54(9):583-587. Published online August 31, 2016; DOI: https://doi.org/10.1007/s12275-016-6322-2

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Abstract PDF

RIG-I is a cytosolic receptor recognizing virus-specific RNA structures and initiates an antiviral signaling that induces the production of interferons and proinflammatory cytokines. Because inappropriate RIG-I signaling affects either viral clearance or immune toxicity, multiple regulations of RIG-I have been investigated since its discovery as the viral RNA detector. In this review, we describe the recent progress in research on the regulation of RIG-I activity or abundance. Specifically, we focus on the mechanism that modulates RIGI- dependent antiviral response through post-translational modifications of or protein-protein interactions with RIG-I.

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Retracted Publication

Interferon-mediated antiviral activities of Angelica tenuissima Nakai and its active components: Prasanna Weeratunga , Md Bashir Uddin , Myun Soo Kim , Byeong-Hoon Lee , Tae-Hwan Kim , Ji-Eun Yoon , Jin Yeul Ma , Hongik Kim , Jong-Soo Lee; J. Microbiol. 2016;54(1):57-70. Published online January 5, 2016; DOI: https://doi.org/10.1007/s12275-016-5555-4

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Abstract PDF

Angelica tenuissima Nakai is a widely used commodity in traditional medicine. Nevertheless, no study has been conducted on the antiviral and immune-modulatory properties of an aqueous extract of Angelica tenuissima Nakai. In the present study, we evaluated the antiviral activities and the mechanism of action of an aqueous extract of Angelica tenuissima Nakai both in vitro and in vivo. In vitro, an effective dose of Angelica tenuissima Nakai markedly inhibited the replication of Influenza A virus (PR8), Vesicular stomatitis virus (VSV), Herpes simplex virus (HSV), Coxsackie virus, and Enterovirus (EV-71) on epithelial (HEK293T/HeLa) and immune (RAW264.7) cells. Such inhibition can be described by the induction of the antiviral state in cells by antiviral, IFNrelated gene induction and secretion of IFNs and pro-inflammatory cytokines. In vivo, Angelica tenuissima Nakai treated BALB/c mice displayed higher survivability and lower lung viral titers when challenged with lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3, and H9N2). We also found that Angelica tenuissima Nakai can induce the secretion of IL-6, IFN-λ, and local IgA in bronchoalveolar lavage fluid (BALF) of Angelica tenuissima Nakai treated mice, which correlating with the observed prophylactic effects. In HPLC analysis, we found the presence of several compounds in the aqueous fraction and among them; we evaluated antiviral properties of ferulic acid. Therefore, an extract of Angelica tenuissima Nakai and its components, including ferulic acid, play roles as immunomodulators and may be potential candidates for novel anti-viral/anti-influenza agents.

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Research Support, Non-U.S. Gov'ts

Antiviral effects of Lactobacillus ruminis SPM0211 and Bifidobacterium longum SPM1205 and SPM1206 on rotavirus-infected Caco-2 cells and a neonatal mouse model: Joo Yeon Kang , Do Kyung Lee , Nam Joo Ha , Hea Soon Shin; J. Microbiol. 2015;53(11):796-803. Published online October 28, 2015; DOI: https://doi.org/10.1007/s12275-015-5302-2

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Abstract

Rotavirus is worldwide cause of severe gastroenteritis including severe diarrhea and fatal dehydration in infants and young children. There is an available vaccination program for preventing rotavirus infection, but it has limits and restrictions. Probiotics therapy could be an alternative
method
of antiviral prevention and modulation against rotavirus infection. In this study, we screened the antiviral activity of probiotic bacteria such as 3 Lactobacillus spp. and 14 Bifidobacterium spp. isolated from young Korean. Three of the bacteria, Lactobacillus ruminis SPM0211, Bifidobacterium longum SPM1205, and SPM1206, inhibited human strain Wa rotavirus infection in Caco-2 cells. Furthermore, these bacterial strains inhibited rotavirus replication in a rotavirus-infected neonatal mouse model. To clarify the mechanism of inhibition, we investigated gene expression of Interferon (IFN)-signaling components and IFN-inducible antiviral effectors. All 3 probiotics increased IFN-α and IFN- β levels compared with the control. Gene expression of IFNsignaling components and IFN-inducible antiviral effectors also increased. Overall, these results indicate that L. ruminis SPM0211, B. longum SPM1205 and 1206 efficiently inhibit rotavirus replication in vitro and in vivo. Especially, the antiviral effect of Lactobacillus ruminis SPM0211 is worthy of notice. This is the first report of L. ruminis with antiviral activity. Anti-rotaviral effects of the 3 probiotics are likely due to their modulation of the immune response through promoting type I IFNs, which are key regulators in IFN signaling pathway.

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Cyclic Dipeptides from Lactic Acid Bacteria Inhibit Proliferation of the Influenza A Virus: Min-Kyu Kwak , Rui Liu , Jun-Oh Kwon , Min-Kyu Kim , Andrew HyoungJin Kim , Sa-Ouk Kang; J. Microbiol. 2013;51(6):836-843. Published online December 19, 2013; DOI: https://doi.org/10.1007/s12275-013-3521-y

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We isolated Lactobacillus plantarum LBP-K10 from the traditional Korean fermented food kimchi. When organic acids were removed, the culture filtrate of this isolate showed high antiviral activity (measured using a plaque-forming assay) against the influenza A (H3N2) virus. Two fractions that were active against influenza A virus were purified from the culture filtrate using a C18 column with high-performance liquid chromatography. These active fractions were crystallized and identified to be the cyclic dipeptides cis-cyclo (L-Leu-L-Pro) and cis-cyclo(L-Phe-L-Pro) using gas chromatography-mass spectrometry; this identification was confirmed by X-ray crystallography. These cyclic dipeptides were identified in the culture filtrate of other lactic acid bacteria, including Lactobacillus spp., Leuconostoc spp., Weissella spp., and Lactococcus lactis.

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DBA/2 Mouse as an Animal Model for Anti-influenza Drug Efficacy Evaluation: Jin Il Kim , Sehee Park , Sangmoo Lee , Ilseob Lee , Jun Heo , Min-Woong Hwang , Joon-Yong Bae , Donghwan Kim , Seok-Il Jang , Mee Sook Park , Man-Seong Park; J. Microbiol. 2013;51(6):866-871. Published online December 19, 2013; DOI: https://doi.org/10.1007/s12275-013-3428-7

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Influenza viruses are seasonally recurring human pathogens. Vaccines and antiviral drugs are available for influenza. However, the viruses, which often change themselves via antigenic drift and shift, demand constant efforts to update vaccine antigens every year and develop new agents with broad-spectrum antiviral efficacy. An animal model is critical for such efforts. While most human influenza viruses are unable to kill BALB/c mice, some strains have been shown to kill DBA/2 mice without prior adaptation. Therefore, in this study, we explored the feasibility of employing DBA/2 mice as a model in the development of anti-influenza drugs. Unlike the BALB/c strain, DBA/2 mice were highly susceptible and could be killed with a relatively low titer (50% DBA/2 lethal dose = 102.83 plaque-forming units) of the A/ Korea/01/2009 virus (2009 pandemic H1N1 virus). When treated with a neuraminidase inhibitor, oseltamivir phosphate, infected DBA/2 mice survived until 14 days postinfection. The reduced morbidity of the infected DBA/2 mice was also consistent with the oseltamivir treatment. Taking these data into consideration, we propose that the DBA/2 mouse is an excellent animal model to evaluate antiviral efficacy against influenza infection and can be further utilized for combination therapies or bioactivity models of existing and newly developed anti-influenza drugs.

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The Anti-influenza Virus Effect of Phellinus igniarius Extract: Sangmoo Lee , Jin Il Kim , Jun Heo , Ilseob Lee , Sehee Park , Min-Woong Hwang , Joon-Yong Bae , Mee Sook Park , Hyoung Jin Park , Man-Seong Park; J. Microbiol. 2013;51(5):676-681. Published online October 31, 2013; DOI: https://doi.org/10.1007/s12275-013-3384-2

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Herbal medicine has been used in the orient for thousands of years to treat large and small ailments, including microbial infections. Although there are treatments for influenza virus infection, there is no treatment for drug-resistant viruses. It is time that we explored and exploited the multicomponent nature of herbal extracts as multi-drug combination therapies. Here, we present data on the anti-influenza virus effect of a medicinal mushroom, Phellinus igniarius. The P. igniarius water extract was effective against influenza A and B viruses, including 2009 pandemic H1N1, human H3N2, avian H9N2, and oseltamivir-resistant H1N1 viruses. Virological assays revealed that the extract may interfere with one or more early events in the influenza virus replication cycle, including viral attachment to the target cell. Therefore, our results provide new insights into the use of P. igniarius as an anti-influenza medicine.

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NOTE] GFP-Expressing Influenza A Virus for Evaluation of the Efficacy of Antiviral Agents: Jin Il Kim , Sehee Park , Ilseob Lee , Sangmoo Lee , Saem Shin , Yongkwan Won , Min-Woong Hwang , Joon-Yong Bae , Jun Heo , Hye-Eun Hyun , Hyejin Jun , Soon Sung Lim , Man-Seong Park; J. Microbiol. 2012;50(2):359-362. Published online April 27, 2012; DOI: https://doi.org/10.1007/s12275-012-2163-9

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To address its value as a screening tool in the development of antiviral drugs, a recombinant influenza virus expressing green fluorescent protein (rPR8-GFP virus) was investigated in vitro and in vivo. The inhibition of viral growth by a neuraminidase inhibitor in the cells or lower respiratory tracts of mice could be visualized by the level of fluorescence. In addition, the rPR8-GFP virus exhibited high pathogenicity in mice. Taken together, these results suggest that the rPR8-GFP virus can be a useful tool for the rapid identification of antiviral drugs active against influenza viruses.

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The anti-influenza virus effect of Phellinus igniarius extract
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In Vitro Antiviral Activity of Red Alga, Polysiphonia morrowii Extract and Its Bromophenols Against Fish Pathogenic Infectious Hematopoietic Necrosis Virus and Infectious Pancreatic Necrosis Virus: Su-Yeun Kim , Seok Ryel Kim# , Myung-Joo Oh , Sung-Ju Jung , So Young Kang; J. Microbiol. 2011;49(1):102-106. Published online March 3, 2011; DOI: https://doi.org/10.1007/s12275-011-1035-z

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Our previous investigation revealed that 80% methanolic extract of the red alga Polysiphonia morrowii has significant antiviral activities against fish pathogenic viruses, infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV). The present study was conducted to identify compounds attributed for its antiviral activities and investigate their antiviral activities against IHNV and IPNV. Activityguided fractionation for 80% methanolic extract of Polysiphonia morrowii using a cell-based assay measuring virus-induced cytopathic effect (CPE) on cells yielded a 90% methanolic fraction, which showed the highest antiviral activity against both viruses among fractions yielded from the extract. From the fraction, two bromophenols were isolated and identified as 3-bromo-4,5-dihydroxybenzyl methyl ether (1) and 3-bromo-4,5-dihydroxybenzaldehyde (2) based on spectroscopic analyses. For both compounds, the concentrations to inhibit 50% of flounder spleen cell (FSP cell) proliferation (CC50) and each viral replication (EC50) were measured. In the pretreatment test, 3-bromo-4,5-dihydroxybenzyl methyl ether (1) and 3-bromo-4,5-dihydroxybenzaldehyde (2) exhibited significant antiviral activities showing selective index values (SI = CC50/EC50) of 20 to 42 against both IHNV and IPNV. In direct virucidal test, 3-bromo-4,5-dihydroxybenzyl methyl ether (1) showed significant antiviral activites against both viruses while 3-bromo-4,5-dihydroxybenzaldehyde (2) was significantly effective against only IHNV. Although antiviral efficacies of both compounds against IHNV and IPNV were lower than those of ribavirin used as a positive control, our findings suggested that the red alga Polysiphonia morrowii and isolated two bromophenols may have potential as a therapeutic agent against fish viral diseases.

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Measurement of Antiviral Activities Using Recombinant Human Cytomegalovirus: Byung-Hak Song , Gyu-Cheol Lee , Chan-Hee Lee; J. Microbiol. 2000;38(4):255-259.

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Abstract PDF: For rapid and sensitive measurement of antiviral activities, application of a recombinant virus containing firefly luciferase gene was attempted. Recombinant human cytomegalovirus (HCMV) containing luciferase gene driven by HCMV late gene pp28 promoter (HCMV/pp28-luc) was used to test the antiviral activities of three known compounds and the result was compared with results from the conventional plaque assay for measuring the production of infectious viruses. When human fibroblast cells were infected with HCMV/pp28-luc, luciferase activity was observed at 2 days after infection and reached maximum at 6 days after infection, whereas the production of infectious virus was maximal at 4 days after infection. The antiviral activities of ganciclovir, acyclovir, and papaverine were measured in HFF cells infected with HCMV/pp28-luc and the luciferase activity was compared with the infectious virus titers. Luciferase activity decreased as the concentration of ganciclovir or papaverine increased, while there was a slight decrease in luciferase activity with acyclovir. The level of the decrease in luciferase activity was comparable to the level of decrease in the production of infectious virus. Therefore, the antiviral assay using recombinant virus HCMV/pp28-luc resulted in sensitivity similar to the conventional plaque assay with a significant reduction in assay time.

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