Dense Granule Protein-7 (GRA-7) of Toxoplasma gondii inhibits viral replication in vitro and in vivo

Weeratunga, Prasanna,Herath, Thilina U. B.,Kim, Tae-Hwan,Lee, Hyun-Cheol,Kim, Jae-Hoon,Lee, Byeong-Hoon,Lee, Eun-Seo,Chathuranga, Kiramage,Chathuranga, W. A. Gayan,Yang, Chul-Su,Ma, Jin Yeul,Lee, Jong MICROBIOLOGICAL SOCIETY OF KOREA 2017 JOURNAL OF MICROBIOLOGY -SEOUL- Vol. No.

<P>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 (VSV-GFP), 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.</P>

RETRACTED ARTICLE: Interferon-mediated antiviral activities of Angelica tenuissima Nakai and its active components

Weeratunga, Prasanna,Uddin, Md Bashir,Kim, Myun Soo,Lee, Byeong-Hoon,Kim, Tae-Hwan,Yoon, Ji-Eun,Ma, Jin Yeul,Kim, Hongik,Lee, Jong-Soo Springer-Verlag 2016 The journal of microbiology Vol.54 No.1

<P>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, IFN-related 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-lambda, 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.</P>

Dense Granule Protein-7 (GRA-7) of Toxoplasma gondii inhibits viral replication in vitro and in vivo

Prasanna Weeratunga,틸리나,김태환,이현철,김재훈,이병훈,이은서,Kiramage Chathuranga,W. A. Gayan Chathuranga,양철수,마진열,이종수 한국미생물학회 2017 The journal of microbiology Vol.55 No.11

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.

The anti-Influenza effect of a water soluble herbal extract from Salvia miltiorrhiza (Danshen) in vivo

Eun-Seo Lee,Myun Soo Kim,Prasanna Weeratunga,Hyun-Cheol Lee,Kiramage Chathuranga,Jin Yeul Ma,김홍익,이종수 충북대학교 동물의학연구소 2018 Journal of Biomedical and Translational Research Vol.19 No.1

Salvia miltiorrhiza (Danshen) is perennial plant and commonly used in traditional Chinese medicine to treat numerous diseases like cardiovascular and cerebrovascular diseases, coronary heart disease, myocardial infarction, stroke and some viral diseases. Nevertheless, no study has been conducted on the antiviral properties of crude extract of Salvia miltiorrhiza against Influenza virus. In an attempt to identify new potential anti-influenza virus agents, 200 natural oriental herbal medicines were screened and we found that Salvia miltiorrhiza has a potential anti-influenza effect. Therefore, in this study, we investigated the protective effect of aqueous extract from Salvia miltiorrhiza against divergent influenza A subtypes using murine model of influenza A infection. Effective dose of aqueous extracts of Salvia miltiorrhiza in BALB/c mice displayed higher survival rate and lower lung viral titers when challenged with lethal doses of influenza A subtypes ({A/Aquatic bird/Korea/W81/2005(H5N2)}, {A/PR/8/34(H1N1)}, {A/Aquatic bird/Korea/W44/2005(H7N3)} and {A/Chicken/Korea/116/2004(H9N2)}). In vivo results exhibited that Salvia miltiorrhiza induced prophylactic effect in BALB/c mice against Influenza virus by disrupting viral replication or preventing viral infection by creating an antiviral state in the lungs. Taken together, the use of aqueous extracts of Salvia miltiorrhiza as an orally active antiviral agent, will be potential candidates for prophylactic treatments against Influenza A virus for humans and animals.

Coptidis Rhizoma extract inhibits replication of respiratory syncytial virus in vitro and in vivo by inducing antiviral state

이병훈,Kiramage Chathuranga,Md Bashir Uddin,Prasanna Weeratunga,김면수,조원경,김홍익,마진열,이종수 한국미생물학회 2017 The journal of microbiology Vol.55 No.6

Coptidis Rhizoma is derived from the dried rhizome of Ranunculaceous plants and is a commonly used traditional Chinese medicine. Although Coptidis Rhizoma is commonly used for its many therapeutic effects, antiviral activity against respiratory 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 interferon- 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 palmatine was related to the antiviral properties and immunemodulation effect. Taken together, an extract of Coptidis Rhizoma 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.