Inhibition of Chikungunya virus by an Adenosine Analog targeting the SAM ‐dependent nsP1 methyltransferase

AbstractAlphaviruses, including Chikungunya (CHIKV) and Venezuelan equine encephalitis virus (VEEV), are among the leading causes of recurrent epidemics all over the world. Alphaviral non ‐structural protein 1 (nsP1) orchestrates the capping of nascent viral RNA via its S‐adenosyl methionine‐dependent N‐7‐methyltransferase (MTase) and guanylyltransferase activities. Here, we developed and validated a novel capillary electrophoresis (CE)‐based assay for measuring the MTase activity of purified VEEV and CHIKV nsP1. We employed the assay to assess the MTase inhibition efficiency of a few adenosine analogs and identified 5‐iodotubercidin (5‐IT) as an inhibitor of nsP1. The antiviral potency of 5‐IT was evaluatedin vitro using a combination of cell ‐based assays, which suggest that 5‐IT is efficacious against CHIKV in cell culture (EC50: 0. 409 µM).
Source: FEBS Letters - Category: Biochemistry Authors: Tags: RESEARCH ARTICLES Source Type: research

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Alphaviruses, including Chikungunya (CHIKV) and Venezuelan equine encephalitis virus (VEEV), are among the leading causes of recurrent epidemics all over the world. Alphaviral nonstructural protein 1 (nsP1) orchestrates the capping of nascent viral RNAvia its S ‐adenosyl methionine‐dependent N‐7‐methyltransferase (MTase) and guanylyltransferase activities. Here, we developed and validated a novel capillary electrophoresis (CE)‐based assay for measuring the MTase activity of purified VEEV and CHIKV nsP1. We employed the assay to assess the MTase i nhibition efficiency of a few adenosine analogs and identified 5‐...
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Article Source Type: research
Discussion Dengue is an important arboviral infection that affects about 40% of the world population. It is found mainly in topical and subtropical areas of the world mainly in developing countries but it range is spreading including the United States. A review of common arboviruses can be found here. It is a flaviavirus with 4 distinct serotypes named DENV-1 through DENV-4 and is spread by A. aegypti a day biting mosquito. Infection with one serotype confers immunity to that serotype but not the others. It does offer some protection for cross-infection but this only lasts a few months. Incubation period is 3-14 days with ...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Adriano Queiroz1, Isabella Fernanda Dantas Pinto2, Maricélia Lima3, Marta Giovanetti1,4, Jaqueline Goes de Jesus1, Joilson Xavier1, Fernanda Khouri Barreto5, Gisele André Baptista Canuto6, Helineide Ramos do Amaral7, Ana Maria Bispo de Filippis4, Denise Lima Mascarenhas8, Melissa Barreto Falcão8, Normeide Pedreira Santos8, Vasco Ariston de Carvalho Azevedo9, Marcos Yukio Yoshinaga2*, Sayuri Miyamoto2 and Luiz Carlos Junior Alcantara1,4,10* 1Laboratório de Patologia Experimental, Instituto Gonçalo Moniz, Salvador, Brazil 2Departamento de Bioquímica, Instituto de Quími...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Conclusions Apart West Nile virus (78), thousands of congenital microcephaly cases, fetal brain tissue damage and neurological syndromes have been associated with ZIKV infection. Unfortunately, the epidemics of this mosquito born, and a relative stable virus is on a rise. Although congenital microcephaly is a rare disorder however, due to lack of standardized diagnostic test facilities, the incidence in the geographically widespread ZIKV epidemic regions is higher. Animals studies showed that ZIKV is a neurotropic virus. It directly targets the developing embryonic brain cells by inducing apoptosis, cell-cycle arrest, and...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Conclusion and Perspectives Arbovirus infections, such as CHIKV, have been growing worldwide and are becoming a major public health problem, especially in immuno-compromised classes such as children and the elderly. CHIKV is dangerous since it can cause arthritis, fever and other impairments, making it necessary to seek new ways to counter the proliferation of this virus. Knowing the vector’s competence is fundamentally important, including an understanding of the vector virus interaction and the modulation of this interaction. Despite advances in the knowledge of mosquito competence in the transmission of CHIKV, li...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Abstract Emerging arthropod-borne viruses (arboviruses), such as chikungunya and Zika viruses, are a major threat to public health in countries like Brazil where biodiversity is high and medical care is sometimes precarious. West Nile fever is a disease caused by the West Nile Virus (WNV), an RNA virus belonging to the Flaviviridae family. It is transmitted by infected mosquitoes to numerous animals like birds, reptiles and mammals, including human and non-human primates. In the last decade, the number of reported cases of WNV infection in humans and animals has increased in the Americas. Circulation of WNV in forests and ...
Source: Revista da Sociedade Brasileira de Medicina Tropical - Category: Tropical Medicine Source Type: research
In this study, we were able to demonstrate that our measure for mosquito-borne viral suitability is informative in the context of Myanmar, despite the lack of ento-epidemiological datasets with high spatio-temporal resolution. By estimating suitability through climate variables and known ento-epidemiological parameters, we were able to project mosquito-born virus (MBV) suitability at the district level, a resolution for which epidemiological data and mosquito abundance measures are not generally available. Here, we discuss the national and subnational public health and control implications for MBVs in the context of our pr...
Source: PLOS Currents Outbreaks - Category: Epidemiology Authors: Source Type: research
Summary Mosquito‐borne diseases such as dengue, yellow fever and, more recently, Chikungunya virus (CHIKV) and Zika virus (ZIKV) have a great impact in the public health. In addition, the presence of such viruses might have an impact on wild animal conservation as well as their possible role as animal reservoir. Here, we performed a serological survey searching for antibodies against a panel of flaviviruses [ZIKV, Dengue virus (DENV), Yellow Fever virus (YFV), West Nile virus (WNV), Saint Louis Encephalitis virus (SLEV), Ilheus virus (ILHV) and Rocio virus (ROCV)] using plaque reduction neutralization test (PRNT90) in bo...
Source: Transboundary and Emerging Diseases - Category: Veterinary Research Authors: Tags: SHORT COMMUNICATION Source Type: research
AbstractMosquitos are responsible for a number of protozoal and viral diseases. Malaria, dengue, Japanese encephalitis (JE) and chikungunya epidemics occur commonly all over the world, leading to marked mortality and morbidity in children. Zika, Yellow fever and West Nile fever are others requiring prevention. Environmental control and mosquito bite prevention are useful in decreasing the burden of disease but vaccination has been found to be most cost-effective and is the need of the hour. RTS,S/AS01 vaccine is the first malaria vaccine being licensed for use againstP. falciparum malaria. Dengvaxia (CYD-TDV) against dengu...
Source: Indian Journal of Pediatrics - Category: Pediatrics Source Type: research
Abstract Chikungunya, an alphavirus infection presenting with fever, rash, and polyarthritis, is most often an acute febrile illness. Neurologic complications of chikungunya infection have been reported. Here we report the clinical and neuroimaging data of 2 patients with chikungunya-associated encephalitis during the recent Brazilian epidemic.
Source: Revista da Sociedade Brasileira de Medicina Tropical - Category: Tropical Medicine Source Type: research
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