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Article ; Online: Sofosbuvir Suppresses the Genome Replication of DENV1 in Human Hepatic Huh7 Cells.

Kurosawa, Madoka / Kato, Fumihiro / Hishiki, Takayuki / Ito, Saori / Fujisawa, Hiroki / Yamaguchi, Tatsuo / Moriguchi, Misato / Hosokawa, Kohei / Watanabe, Tadashi / Saito-Tarashima, Noriko / Minakawa, Noriaki / Fujimuro, Masahiro

International journal of molecular sciences

2024 Volume 25, Issue 4

Abstract: Dengue virus (DENV) causes dengue fever and dengue hemorrhagic fever, and DENV infection kills 20,000 people annually worldwide. Therefore, the development of anti-DENV drugs is urgently needed. Sofosbuvir (SOF) is an effective drug for HCV-related ... ...

Abstract	Dengue virus (DENV) causes dengue fever and dengue hemorrhagic fever, and DENV infection kills 20,000 people annually worldwide. Therefore, the development of anti-DENV drugs is urgently needed. Sofosbuvir (SOF) is an effective drug for HCV-related diseases, and its triphosphorylated metabolite inhibits viral RNA synthesis by the RNA-dependent RNA polymerase (RdRp) of HCV. (2'R)-2'-Deoxy-2'-fluoro-2'-methyluridine (FMeU) is the dephosphorylated metabolite produced from SOF. The effects of SOF and FMeU on DENV1 replication were analyzed using two DENV1 replicon-based methods that we previously established. First, a replicon-harboring cell assay showed that DENV1 replicon replication in human hepatic Huh7 cells was decreased by SOF but not by FMeU. Second, a transient replicon assay showed that DENV1 replicon replication in Huh7 cells was decreased by SOF; however, in hamster kidney BHK-21 cells, it was not suppressed by SOF. Additionally, the replicon replication in Huh7 and BHK-21 cells was not affected by FMeU. Moreover, we assessed the effects of SOF on infectious DENV1 production. SOF suppressed infectious DENV1 production in Huh7 cells but not in monkey kidney Vero cells. To examine the substrate recognition of the HCV and DENV1 RdRps, the complex conformation of SOF-containing DENV1 RdRp or HCV RdRp was predicted using AlphaFold 2. These results indicate that SOF may be used as a treatment for DENV1 infection.
MeSH term(s)	Animals ; Cricetinae ; Chlorocebus aethiops ; Humans ; Sofosbuvir/pharmacology ; Antiviral Agents/pharmacology ; Vero Cells ; RNA-Dependent RNA Polymerase ; Virus Replication ; Hepatitis C ; Hepacivirus/genetics
Chemical Substances	Sofosbuvir (WJ6CA3ZU8B) ; Antiviral Agents ; RNA-Dependent RNA Polymerase (EC 2.7.7.48)
Language	English
Publishing date	2024-02-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25042022
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Dengue Virus Reporter Replicon is a Valuable Tool for Antiviral Drug Discovery and Analysis of Virus Replication Mechanisms.

Kato, Fumihiro / Hishiki, Takayuki

Viruses

2016 Volume 8, Issue 5

Abstract: Dengue, the most prevalent arthropod-borne viral disease, is caused by the dengue virus (DENV), a member of the Flaviviridae family, and is a considerable public health threat in over 100 countries, with 2.5 billion people living in high-risk areas. ... ...

Abstract	Dengue, the most prevalent arthropod-borne viral disease, is caused by the dengue virus (DENV), a member of the Flaviviridae family, and is a considerable public health threat in over 100 countries, with 2.5 billion people living in high-risk areas. However, no specific antiviral drug or licensed vaccine currently targets DENV infection. The replicon system has all the factors needed for viral replication in cells. Since the development of replicon systems, transient and stable reporter replicons, as well as reporter viruses, have been used in the study of various virological aspects of DENV and in the identification of DENV inhibitors. In this review, we summarize the DENV reporter replicon system and its applications in high-throughput screening (HTS) for identification of anti-DENV inhibitors. We also describe the use of this system in elucidation of the mechanisms of virus replication and viral dynamics in vivo and in vitro.
MeSH term(s)	Antiviral Agents/isolation & purification ; Antiviral Agents/pharmacology ; Dengue Virus/drug effects ; Dengue Virus/genetics ; Dengue Virus/physiology ; Drug Discovery/methods ; Genes, Reporter ; Humans ; Staining and Labeling/methods ; Virology/methods ; Virus Replication
Chemical Substances	Antiviral Agents
Keywords	covid19
Language	English
Publishing date	2016-05-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v8050122
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Article ; Online: Epigallocatechin gallate (EGCG) attenuates severe acute respiratory coronavirus disease 2 (SARS-CoV-2) infection by blocking the interaction of SARS-CoV-2 spike protein receptor-binding domain to human angiotensin-converting enzyme 2.

Ohishi, Tomokazu / Hishiki, Takayuki / Baig, Mirza S / Rajpoot, Sajjan / Saqib, Uzma / Takasaki, Tomohiko / Hara, Yukihiko

PloS one

2022 Volume 17, Issue 7, Page(s) e0271112

Abstract: The outbreak of the coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 triggered a global pandemic where control is needed through therapeutic and preventive interventions. This study aims to identify natural compounds ...

Abstract	The outbreak of the coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 triggered a global pandemic where control is needed through therapeutic and preventive interventions. This study aims to identify natural compounds that could affect the fusion between the viral membrane (receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein) and the human cell receptor angiotensin-converting enzyme 2. Accordingly, we performed the enzyme-linked immunosorbent assay-based screening of 10 phytochemicals that already showed numerous positive effects on human health in several epidemiological studies and clinical trials. Among these phytochemicals, epigallocatechin gallate, a polyphenol and a major component of green tea, could effectively inhibit the interaction between the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein and the human cell receptor angiotensin-converting enzyme 2. Alternately, in silico molecular docking studies of epigallocatechin gallate and angiotensin-converting enzyme 2 indicated a binding score of -7.8 kcal/mol and identified a hydrogen bond between R393 and angiotensin-converting enzyme 2, which is considered as a key interacting residue involved in binding with the severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain, suggesting the possible blocking of interaction between receptor-binding domain and angiotensin-converting enzyme 2. Furthermore, epigallocatechin gallate could attenuate severe acute respiratory syndrome coronavirus 2 infection and replication in Caco-2 cells. These results shed insight into identification and validation of severe acute respiratory syndrome coronavirus 2 entry inhibitors.
MeSH term(s)	Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/drug therapy ; COVID-19/metabolism ; COVID-19/virology ; Caco-2 Cells ; Catechin/analogs & derivatives ; Catechin/pharmacology ; Humans ; Molecular Docking Simulation ; Peptidyl-Dipeptidase A/metabolism ; Protein Binding ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Catechin (8R1V1STN48) ; epigallocatechin gallate (BQM438CTEL) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0271112
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Article: Antiviral Activity of CD437 Against Mumps Virus.

Kato, Fumihiro / Nakatsu, Yuichiro / Murano, Keiko / Wakata, Aika / Kubota, Toru / Hishiki, Takayuki / Yamaji, Toshiyuki / Kidokoro, Minoru / Katoh, Hiroshi / Takeda, Makoto

Frontiers in microbiology

2021 Volume 12, Page(s) 751909

Abstract: Many efforts have been dedicated to the discovery of antiviral drug candidates against the mumps virus (MuV); however, no specific drug has yet been approved. The development of efficient screening methods is a key factor for the discovery of antiviral ... ...

Abstract	Many efforts have been dedicated to the discovery of antiviral drug candidates against the mumps virus (MuV); however, no specific drug has yet been approved. The development of efficient screening methods is a key factor for the discovery of antiviral candidates. In this study, we evaluated a screening method using an
Language	English
Publishing date	2021-11-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2021.751909
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Article ; Online: Suppression of dengue virus replication by the French maritime pine extract Pycnogenol®.

Hossain, Kazi Anowar / Akhter, Rupaly / Rashid, Md Haroon Or / Akter, Lipi / Utsunomiya, Masashi / Kitab, Bouchra / Ngwe Tun, Mya Myat / Hishiki, Takayuki / Kohara, Michinori / Morita, Kouichi / Tsukiyama-Kohara, Kyoko

Virus research

2023 Volume 339, Page(s) 199244

Abstract: Dengue virus (DENV) is mainly found in the tropics and infects approximately 400 million people annually. However, no clinically available therapeutic agents specific to dengue have been developed. Here, we examined the potential antiviral effects of the ...

Abstract	Dengue virus (DENV) is mainly found in the tropics and infects approximately 400 million people annually. However, no clinically available therapeutic agents specific to dengue have been developed. Here, we examined the potential antiviral effects of the French maritime pine extract Pycnogenol® (PYC) against DENV because we previously found that the extract exerts antiviral effects on hepatitis C virus, which belongs to the Flavivirus family. First, we examined the efficacy of PYC against DENV1, 2, 3, and 4 serotypes and determined that it had a dose-dependent suppressive effect on the viral load, especially in the supernatant. This inhibitory effect of PYC may target the late stages of infection such as maturation and secretion, but not replication. Next, we examined the efficacy of PYC against DENV infection in type I interferon (IFN) receptor knockout mice (A129). As the propagation of DENV2 was the highest among the four serotypes, we used this serotype in our murine model experiments. We found that PYC significantly inhibited DENV2 replication in mice on day 4 without significantly decreasing body weight or survival ratio. We further examined the mechanism of action of PYC in DENV2 infection by characterizing the main PYC targets among the host (viral) factors and silencing them using siRNA. Silencing long noncoding-interferon-induced protein (lnc-IFI)-44, polycystic kidney disease 1-like 3 (Pkd1l3), and ubiquitin-specific peptidase 31 (Usp31) inhibited the replication of DENV2. Thus, the results of this study shed light on the inhibitory effects of PYC on DENV replication and its underlying mechanisms.
MeSH term(s)	Humans ; Mice ; Animals ; Antiviral Agents/pharmacology ; Dengue/drug therapy ; Virus Replication ; Pinus
Chemical Substances	pycnogenols (50JZ5Z98QY) ; Antiviral Agents
Language	English
Publishing date	2023-10-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2023.199244
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Article ; Online: Dengue Virus Reporter Replicon is a Valuable Tool for Antiviral Drug Discovery and Analysis of Virus Replication Mechanisms

Fumihiro Kato / Takayuki Hishiki

Viruses, Vol 8, Iss 5, p

2016 Volume 122

Abstract	Dengue, the most prevalent arthropod-borne viral disease, is caused by the dengue virus (DENV), a member of the Flaviviridae family, and is a considerable public health threat in over 100 countries, with 2.5 billion people living in high-risk areas. However, no specific antiviral drug or licensed vaccine currently targets DENV infection. The replicon system has all the factors needed for viral replication in cells. Since the development of replicon systems, transient and stable reporter replicons, as well as reporter viruses, have been used in the study of various virological aspects of DENV and in the identification of DENV inhibitors. In this review, we summarize the DENV reporter replicon system and its applications in high-throughput screening (HTS) for identification of anti-DENV inhibitors. We also describe the use of this system in elucidation of the mechanisms of virus replication and viral dynamics in vivo and in vitro.
Keywords	dengue virus ; flavivirus ; reporter replicon ; replication ; antiviral drug ; high-throughput screening ; Microbiology ; QR1-502 ; Science ; Q
Subject code	570
Language	English
Publishing date	2016-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Antiviral activities of mycophenolic acid and IMD-0354 against SARS-CoV-2.

Kato, Fumihiro / Matsuyama, Shutoku / Kawase, Miyuki / Hishiki, Takayuki / Katoh, Hiroshi / Takeda, Makoto

Microbiology and immunology

2020 Volume 64, Issue 9, Page(s) 635–639

Abstract: In this study, the anti-severe acute respiratory syndrome coronavirus-2 (anti-SARS-CoV-2) activity of mycophenolic acid (MPA) and IMD-0354 was analyzed. These compounds were chosen based on their antiviral activities against other coronaviruses. Because ... ...

Abstract	In this study, the anti-severe acute respiratory syndrome coronavirus-2 (anti-SARS-CoV-2) activity of mycophenolic acid (MPA) and IMD-0354 was analyzed. These compounds were chosen based on their antiviral activities against other coronaviruses. Because they also inhibit dengue virus (DENV) infection, other anti-DENV compounds/drugs were also assessed. On SARS-CoV-2-infected VeroE6/TMPRSS2 monolayers, both MPA and IMD-0354, but not other anti-DENV compounds/drugs, showed significant anti-SARS-CoV-2 activity. Although MPA reduced the viral RNA level by only approximately 100-fold, its half maximal effective concentration was as low as 0.87 µ m, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets the coronaviral papain-like protease and an in-depth study on its mechanism of action would be useful in the development of novel anti-SARS-CoV-2 drugs.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Benzamides/pharmacology ; Betacoronavirus/drug effects ; COVID-19 ; Chlorocebus aethiops ; Coronavirus Infections/drug therapy ; Coronavirus Infections/virology ; Dengue Virus/drug effects ; Humans ; Mycophenolic Acid/pharmacology ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Vero Cells ; Virus Replication/drug effects
Chemical Substances	Antiviral Agents ; Benzamides ; N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide (76145IS906) ; Mycophenolic Acid (HU9DX48N0T)
Keywords	covid19
Language	English
Publishing date	2020-07-25
Publishing country	Australia
Document type	Journal Article
ZDB-ID	224792-6
ISSN	1348-0421 ; 0385-5600
ISSN (online)	1348-0421
ISSN	0385-5600
DOI	10.1111/1348-0421.12828
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Article ; Online: Mpox Neutralizing Antibody Response to LC16m8 Vaccine in Healthy Adults.

Morino, Eriko / Mine, Sohtaro / Tomita, Noriko / Uemura, Yukari / Shimizu, Yosuke / Saito, Sho / Suzuki, Tetsuya / Okumura, Nobumasa / Iwasaki, Haruka / Terada, Junko / Ainai, Akira / Sakai, Yusuke / Park, Eunsil / Seki, Sayuri / Akazawa, Daisuke / Shimojima, Masayuki / Shiwa-Sudo, Nozomi / Virhuez-Mendoza, Milagros / Miyauchi, Kosuke /

NEJM evidence

2024 Volume 3, Issue 3, Page(s) EVIDoa2300290

Abstract: Mpox Neutralizing Antibody Response to LC16m8 VaccineIn this study of 50 healthy volunteers in Japan, a smallpox vaccine (LC16m8) exhibited a robust neutralizing antibody response against two strains of the mpox virus. With a 94% "take" rate by day 14, ... ...

Abstract	Mpox Neutralizing Antibody Response to LC16m8 VaccineIn this study of 50 healthy volunteers in Japan, a smallpox vaccine (LC16m8) exhibited a robust neutralizing antibody response against two strains of the mpox virus. With a 94% "take" rate by day 14, seroconversion rates on day 28 were 72 and 70% against the Zr599 and Liberia strains, respectively, decreasing to 30% for both on day 168; no serious adverse events occurred.
MeSH term(s)	Adult ; Humans ; Mpox (monkeypox) ; Vaccines ; Smallpox Vaccine ; Antibodies, Neutralizing ; Antigens, Viral
Chemical Substances	Vaccines ; Smallpox Vaccine ; Antibodies, Neutralizing ; Antigens, Viral
Language	English
Publishing date	2024-02-27
Publishing country	United States
Document type	Journal Article
ISSN	2766-5526
ISSN (online)	2766-5526
DOI	10.1056/EVIDoa2300290
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Article ; Online: Antiviral activities of mycophenolic acid and IMD‐0354 against SARS‐CoV‐2

Kato, Fumihiro / Matsuyama, Shutoku / Kawase, Miyuki / Hishiki, Takayuki / Katoh, Hiroshi / Takeda, Makoto

Microbiology and Immunology

2020 Volume 64, Issue 9, Page(s) 635–639

Keywords	Immunology ; Microbiology ; Virology ; covid19
Language	English
Publisher	Wiley
Publishing country	us
Document type	Article ; Online
ZDB-ID	224792-6
ISSN	1348-0421 ; 0385-5600
ISSN (online)	1348-0421
ISSN	0385-5600
DOI	10.1111/1348-0421.12828
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Hirsutine, an Indole Alkaloid of

Hishiki, Takayuki / Kato, Fumihiro / Tajima, Shigeru / Toume, Kazufumi / Umezaki, Masahito / Takasaki, Tomohiko / Miura, Tomoyuki

Frontiers in microbiology

2017 Volume 8, Page(s) 1674

Abstract: Dengue virus (DENV) is transmitted to humans ... ...

Abstract	Dengue virus (DENV) is transmitted to humans by
Language	English
Publishing date	2017-08-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2017.01674
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