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Antiviral Research

Qiao Xue, Huisheng Liu, Zixiang Zhu, Fan Yang, Qinghong Xue, Xuepeng Cai, Xiangtao Liu, Haixue Zheng
The mechanisms that enable Seneca Valley Virus (SVV) to escape the host innate immune response are not well known. Previous studies demonstrated that SVV 3Cpro suppresses innate immune responses by cleavage of host proteins and degradation of IRF3 and IRF7 protein expression. Here, we showed that SVV 3C protease (3Cpro ) has deubiquitinating activity. Overexpressed 3Cpro inhibits the ubiquitination of cellular substrates, acting on both lysine-48- and lysine-63-linked polyubiquitin chains. SVV infection also possessed deubiquitinating activity...
November 5, 2018: Antiviral Research
Yasuteru Sakurai, Norikazu Sakakibara, Masaaki Toyama, Masanori Baba, Robert A Davey
Ebola virus disease is a severe disease caused by highly pathogenic Ebolaviruses. Although it shows a high mortality rate in humans, currently there is no licensed therapeutic. During the recent epidemic in West Africa, it was demonstrated that administration of antimalarial medication containing amodiaquine significantly lowered mortality rate of patients infected with the virus. Here, in order to improve its antiviral activity, a series of amodiaquine derivatives were synthesized and tested for Ebola virus infection...
November 2, 2018: Antiviral Research
Juan Fidel Osuna-Ramos, José Manuel Reyes-Ruiz, Patricia Bautista-Carbajal, Margot Cervantes-Salazar, Carlos Noe Farfan-Morales, Luis Adrián De Jesús-González, Arianna Mahely Hurtado-Monzón, Rosa María Del Ángel
Despite the importance of Dengue virus (DENV) infection in human health, there is not a fully effective vaccine or antiviral treatment against the infection. Since lipids such as cholesterol are required during DENV infection, its uptake and synthesis are increased in infected cells. Ezetimibe is an FDA-approved drug that reduces cholesterol uptake by inhibiting the endocytosis through Niemman-Pick C1-Like 1 (NPC1L1) receptor, expressed on the membrane of enterocytes and hepatocytes. Our results indicate that an increase in the amount of NPC1L1 occurs on the surface of Huh-7 cells during DENV infection, which correlates with an increase in cholesterol levels...
November 1, 2018: Antiviral Research
Inês Bártolo, Pedro Borrego, Perpétua Gomes, Fátima Gonçalves, Umbelina Caixas, Inês V Pinto, Nuno Taveira
New antiretroviral drugs are needed to treat HIV-2 infected patients failing therapy. Herein, we evaluate the activity of novel reverse transcriptase inhibitors TAF and OBP-601 against primary isolates from HIV-2 infected patients experiencing virologic failure. TAF and OBP-601 were tested against twelve primary isolates obtained from nine drug-experienced patients failing therapy and three drug naïve patients using a single-round infectivity assay in TZM-bl cells. The RT domain of pol was sequenced and the GRADE algorithm was used to identify resistance profiles and mutations...
November 1, 2018: Antiviral Research
Li Song, Dan Xiong, Xilong Kang, Yang Jiao, Xiaohui Zhou, Kaiyue Wu, Yi Zhou, Xinan Jiao, Zhiming Pan
H7N9 influenza virus has an unusually high fatality rate of approximately 40%, and a safe and effective vaccine against this subtype is urgently needed. Flagellin, a Toll-like receptor (TLR) 5 agonist, has been deemed as a potent adjuvant candidate. However, its high antigenicity and potential for causing inflammatory injury might restrict its clinical application. Previously, we demonstrated that a fusion protein, HA1-2-FliC, comprising the hemagglutinin globular head protein (HA1-2) of H7N9 influenza virus and the full-length Salmonella typhimurium flagellin protein (FliC), had high efficiency against H7N9 in mouse and chicken models...
October 30, 2018: Antiviral Research
Nidya A Segura Guerrero, Sapna Sharma, Johan Neyts, Suzanne J F Kaptein
Usutu virus (USUV) is an emerging flavivirus that causes Usutu disease mainly in birds, but infection of mammals such as rodents, bats and horses has also been demonstrated. In addition, human cases (both in immunocompromised and -competent individuals) were also reported. Large outbreaks with other flaviviruses, such as West Nile virus and Zika virus, indicate that one should be vigilant for yet other outbreaks. To allow the identification of inhibitors of USUV replication, we established in vitro antiviral assays, which were validated using a small selection of known flavivirus inhibitors, including the broad-spectrum viral RNA polymerase inhibitor favipiravir (T-705)...
October 29, 2018: Antiviral Research
Jeffrey Langland, Bertram Jacobs, Carl E Wagner, Guillermo Ruiz, Thomas M Cahill
Organic compounds with a caffeoyl moiety (e.g. caffeic acid, rosmarinic acid, chicoric acid, etc.) have antiviral properties towards herpes simplex (HSV), influenza and immunodeficiency viruses (HIV). This study evaluated the HSV antiviral properties of caffeic acid when paired with a variety of metal and other inorganic ions. The results demonstrated that the antiviral activity of caffeic acid increased upwards of 100-fold by the addition of cations, such as Fe3+ , and anionic molecules, such as molybdate and phosphate...
October 28, 2018: Antiviral Research
Ram Kumar, Nitin Khandelwal, Yogesh Chander, Thachamvally Riyesh, Bhupendra N Tripathi, Sudhir Kumar Kashyap, Sanjay Barua, Sunil Maherchandani, Naveen Kumar
A small molecule chemical inhibitor CGP57380 that blocks activation of MAPK interacting kinase 1 (MNK1) was found to significantly suppress buffalopox virus (BPXV) replication. BPXV infection was shown to induce MNK1 activation. Depletion of MNK1 by small interfering RNA (siRNA), blocking activation of extracellular regulated kinase (ERK, an upstream activator of MNK1) and disruption of eIF4E/eIF4G interaction (downstream substrate of MNK1 which plays a central role in cap-dependent translation initiation), resulted in reduced BPXV replication, suggesting that ERK/MNK1/eIF4E signaling is a prerequisite for BPXV replication...
October 28, 2018: Antiviral Research
Monika Aparecida Coronado, Raphael Josef Eberle, Nicole Bleffert, Sophie Feuerstein, Danilo Silva Olivier, Fabio Rogerio de Moraes, Dieter Willbold, Raghuvir Krishnaswamy Arni
Zika virus infection is the focus of much research due to the medical and social repercussions. Due the role of the viral NS2B/NS3 proteinase in maturation of the viral proteins, it had become an attractive antiviral target. Numerous investigations on viral epidemiology, structure and function analysis, vaccines, and therapeutic drugs have been conducted around the world. At present, no approved vaccine or even drugs have been reported. Thus, there is an urgent need to develop therapeutic agents to cure this epidemic disease...
October 28, 2018: Antiviral Research
Ryohei Tsuji, Norio Yamamoto, Sayuri Yamada, Toshio Fujii, Naoki Yamamoto, Osamu Kanauchi
Dengue is a mosquito-borne disease caused by dengue virus (DENV) infection. There is currently no effective vaccine or antiviral treatment available against DENV. In previous studies, we showed that Lactococcus lactis strain Plasma (LC-Plasma) could activate plasmacytoid dendritic cells, which play an important role against virus infection. LC-Plasma administration ameliorated symptoms of viral diseases and its effect appeared to be associated with IFN-α induction. However the precise mechanism of LC-Plasma protection remained unclear...
October 28, 2018: Antiviral Research
Natalia Langenfeld Fuoco, Elaine Raniero Fernandes, Sandriana Dos Ramos Silva, Fernanda Guedes Luiz, Orlando Garcia Ribeiro, Iana Suly Santos Katz
Rabies is a fatal and viral zoonosis that causes acute, progressive encephalitis and remains an important concern in public health. In the last few years, there has been a change in the epidemiological profile of rabies after implementing canine rabies control in the Americas, which has led to a significant increase in both human and pet cases of rabies associated with insectivorous bats. Thus, it is important to understand the pathogenesis caused by Rabies virus (RABV) isolates from insectivorous bats. Viral growth kinetics, cell-to-cell spread and virus uptake in vitro were analyzed for RABV isolates from Eptesicus furiralis and Myotis nigricans...
October 26, 2018: Antiviral Research
Sophie Rogée, Florence Larrous, Dirk Jochmans, Youcef Ben-Khalifa, Johan Neyts, Hervé Bourhy
Rabies virus transmits from animals to humans and causes encephalitis. Every year more than 15 million people receive a post exposure prophylaxis (PEP) treatment that is highly effective in the prevention of rabies disease. However, when clinical symptoms appear, for example in people who did not receive PEP, rabies is almost invariably fatal. Due to the limited access to PEP in some target populations, mostly in Asia and in Africa, rabies causes at least 59,000 deaths a year. PEP is not effective after the onset of symptoms and attempts to develop a treatment for clinical rabies have been unsuccessful...
October 24, 2018: Antiviral Research
Krishani Dinali Perera, Anushka C Galasiti Kankanamalage, Athri D Rathnayake, Amanda Honeyfield, William Groutas, Kyeong-Ok Chang, Yunjeong Kim
Ferret and mink coronaviruses typically cause catarrhal diarrhea in ferrets and minks, respectively. In recent years, however, systemic fatal coronavirus infection has emerged in ferrets, which resembles feline infectious peritonitis (FIP) in cats. FIP is a highly fatal systemic disease caused by a virulent feline coronavirus infection in cats. Despite the importance of coronavirus infections in these animals, there are no effective commercial vaccines or antiviral drugs available for these infections. We have previously reported the efficacy of a protease inhibitor in cats with FIP, demonstrating that a virally encoded 3C-like protease (3CLpro) is a valid target for antiviral drug development for coronavirus infections...
October 19, 2018: Antiviral Research
Asako Murayama, Hiroshi Saitoh, Akiko Takeuchi, Norie Yamada, Takuya Matsumura, Masaaki Shiina, Masamichi Muramatsu, Takaji Wakita, Michio Imawari, Takanobu Kato
Supplementation with vitamin D (VD) has been reported to improve the efficacy of interferon-based therapy for chronic hepatitis C. We found that 25-hydroxyvitamin D3 (25-(OH)D3 ), one of the metabolites of VD, has antiviral effects by inhibiting the infectious virus production of the hepatitis C virus (HCV). In this study, to clarify the underlying mechanisms of the anti-HCV effects, we searched VD derivatives that have anti-HCV effects and identified the common target molecule in the HCV life cycle by using an HCV cell culture system...
October 16, 2018: Antiviral Research
Donald F Smee, Kie-Hoon Jung, Jonna Westover, Brian B Gowen
2'-Fluoro-2'-deoxycytidine (2'-FdC) was reported to inhibit various viruses in vitro, including Borna disease, hepatitis C, Lassa fever, influenza and certain herpes viruses, and is inhibitory to influenza viruses in mice. We investigated the antiviral activity of 2'-FdC against several unrelated bunyaviruses in 50% cytopathic effect (CPE) inhibition assays and, with viruses that cause limited CPE, 90% virus yield reduction (VYR) assays. La Crosse (LACV), Maporal, Punta Toro, Rift Valley fever (RVFV), and San Angelo viruses were inhibited in CPE assays at 2...
October 16, 2018: Antiviral Research
Ke Tang, Shihua He, Xiaoyu Zhang, Jiamei Guo, Qing Chen, Feihu Yan, Logan Banadyga, Wenjun Zhu, Xiangguo Qiu, Ying Guo
The family Arenaviridae consists of numerous enveloped RNA viruses with ambisense coding strategies. Eight arenaviruses, including Lassa virus, are known to cause severe and fatal viral hemorrhagic fever (VHF) in humans, yet vaccines and treatments for disease caused by arenaviruses are very limited. In this study, we screened a natural product library consisting of 131 compounds and identified tangeretin, a polymethoxylated flavone widely present in citrus fruit peels, as a Lassa virus entry inhibitor that blocks viral fusion...
October 16, 2018: Antiviral Research
Jasper Fuk-Woo Chan, Zheng Zhu, Hin Chu, Shuofeng Yuan, Kenn Ka-Heng Chik, Chris Chung-Sing Chan, Vincent Kwok-Man Poon, Cyril Chik-Yan Yip, Xi Zhang, Jessica Oi-Ling Tsang, Zijiao Zou, Kah-Meng Tee, Huiping Shuai, Gang Lu, Kwok-Yung Yuen
Zika virus (ZIKV) is a human-pathogenic flavivirus that has recently emerged as a global public health threat. ZIKV infection may be associated with congenital malformations in infected fetuses and severe neurological and systemic complications in infected adults. There are currently limited treatment options for ZIKV infection. AR-12 (OSU-03012) is a celecoxib derivative cellular kinase inhibitor that has broad-spectrum antiviral activities. In this study, we investigated the antiviral activity and mechanism of AR-12 against ZIKV...
October 13, 2018: Antiviral Research
Chelsea Pinkham, Aslaa Ahmed, Nicole Bracci, Aarthi Narayanan, Kylene Kehn-Hall
Rift Valley fever virus (RVFV) is an enveloped, segmented, negative sense RNA virus that replicates within the host's cytoplasm. To facilitate its replication, RVFV must utilize host cell processes and as such, these processes may serve as potential therapeutic targets. This review summarizes key host cell processes impacted by RVFV infection. Specifically the influence of RVFV on host transcriptional regulation, post-transcriptional regulation, protein half-life and availability, host signal transduction, trafficking and secretory pathways, cytoskeletal modulation, and mitochondrial processes and oxidative stress are discussed...
October 11, 2018: Antiviral Research
Takeshi Noshi, Mitsutaka Kitano, Keiichi Taniguchi, Atsuko Yamamoto, Shinya Omoto, Keiko Baba, Takashi Hashimoto, Kayo Ishida, Yukihiro Kushima, Kazunari Hattori, Makoto Kawai, Ryu Yoshida, Masanori Kobayashi, Tomokazu Yoshinaga, Akihiko Sato, Masatoshi Okamatsu, Yoshihiro Sakoda, Hiroshi Kida, Takao Shishido, Akira Naito
Cap-dependent endonuclease (CEN) resides in the PA subunit of the influenza virus and mediates the critical "cap-snatching" step of viral RNA transcription, which is considered to be a promising anti-influenza target. Here, we describe in vitro characterization of a novel CEN inhibitor, baloxavir acid (BXA), the active form of baloxavir marboxil (BXM). BXA inhibits viral RNA transcription via selective inhibition of CEN activity in enzymatic assays, and inhibits viral replication in infected cells without cytotoxicity in cytopathic effect assays...
October 11, 2018: Antiviral Research
Hao Zhang, Xin Wang, Yuya Wang, Xinyi Pei, Chao Wang, Yan Niu, Ping Xu, Yihong Peng
Activation of the ERK signaling cascade in host cells has been demonstrated to be essential for enterovirus A71 (EV-A71) replication. Our previous study showed that MEK kinase, which specially activated downstream ERK kinase, is an important and potential target against EV-A71. Furthermore, we reported that a series of substituted 3-benzylcoumarins designed and synthesized as well as verified for inhibiting the MEK-ERK cascade were found to be effective on anti-EV-A71. In this study, we further demonstrated that two substituted 3-benzylcoumarins designated as 13 and 14 were more effective anti-MEK/ERK activity, less cytotoxicity and stronger antiviral effect represented by inhibition of viral-induced CPE, the expression of viral proteins and the replication of the viral genome, as well as the production of progeny virions, compared to those of U0126, an available MEK inhibitor, and sorafenib, a multiple-targeted kinase inhibitor in clinical use...
October 11, 2018: Antiviral Research
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