Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus

Powers, Ann M.; Logue, Christopher

doi:10.1099/vir.0.82858-0

Cited by 673 publications

(714 citation statements)

References 84 publications

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“…Chikungunya virus (CHIKV) is are-emerging arboviral infection that is the cause of major public health concern [29]. The Chikungunya viral infection share common symptoms with the dengue viral infection characterized by sudden onset of fever, vomiting, nausea, rashes, arthralgia and myalgia [2,13].…”

Section: Introductionmentioning

confidence: 99%

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

et al. 2017

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Chikungunya fever is an arboviral infection caused by the Chikungunya virus (CHIKV) and is transmitted by Aedes mosquito. The envelope protein (E2) of Chikungunya virus is involved in attachment of virion with the host cell. The present study was conceptualized to determine the structure of E2 protein of CHIKV and to identify the potential viral entry inhibitors. The secondary and tertiary structure of E2 protein was determined using bioinformatics tools. The mutational analysis of the E2 protein suggested that mutations may stabilize or de-stabilize the structure which may affect the structure-function relationship. In silico screening of various compounds from different databases identified two lead molecules i.e. phenothiazine and bafilomycin. Molecular docking and MD simulation studies of the E2 protein and compound complexes was carried out. This analysis revealed that bafilomycin has high docking score and thus high binding affinity with E2 protein suggesting stable protein-ligand interaction. Further, MD simulations suggested that both the compounds were stabilizing E2 protein. Thus, bafilomycin and phenothiazine may be considered as the lead compounds in terms of potential entry inhibitor for CHIKV. Further, these results should be confirmed by comprehensive cell culture, cytotoxic assays and animal experiments. Certain derivatives of phenothiazines can also be explored in future studies for entry inhibitors against CHIKV. The present investigation thus provides insight into protein structural dynamics of the envelope protein of CHIKV. In addition the study also provides information on the dynamics of interaction of E2 protein with entry inhibitors that will contribute towards structure based drug design.

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Section: Introductionmentioning

confidence: 99%

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

et al. 2017

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“…11 Although a small subset of people experience atypical outcomes, which include potentially life-threatening multiorgan failure and encephalitis, epidemiologic studies established unusually severe joint pain as the distinguishing and most common feature of CHIKV infection. 12,13 In addition to joint pain, recent studies have identified severe tenosynovitis and myositis as prominent clinical features of infection. 14 -17 The severe pain is chronic, typically lasting from weeks to months.…”

mentioning

confidence: 99%

A Mouse Model of Chikungunya Virus–Induced Musculoskeletal Inflammatory Disease

Morrison

Oko

Montgomery

et al. 2011

The American Journal of Pathology

240

224

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Chikungunya virus (CHIKV), an emerging mosquitoborne Alphavirus, causes debilitating rheumatic disease in humans that can last for weeks to months. Starting in 2004, a CHIKV outbreak in the Indian Ocean region affected millions of people, and infected travelers introduced CHIKV to new regions. The pathogenesis of CHIKV is poorly understood, and no approved vaccines or specific therapies exist. A major challenge to the study of CHIKV disease is the lack of a small animal model that recapitulates the major outcomes of human infection. In this study, the pathogenesis of CHIKV in C57BL/6J mice was investigated using biological and molecular clones of CHIKV isolated from human serum (CHIKV SL15649). After 14-day-old mice were inoculated with CHIKV SL15649 in the footpad, they displayed reduced weight gain and swelling of the inoculated limb. Histologic analysis of hind limb sections revealed severe necrotizing myositis, mixed inflammatory cell arthritis, chronic active tenosynovitis, and multifocal vasculitis. Interestingly, these disease signs and viral RNA persisted in musculoskeletal tissues for at least 3 weeks after inoculation. This work demonstrates the development of a mouse model of CHIKV infection with clinical manifestations and histopathologic findings that are consistent with the disease signs of CHIKV-infected humans, providing a useful tool for studying viral and host factors that drive CHIKV pathogenesis and for evaluating potential therapeutics against this emerging viral disease.

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“…Outbreaks occurred throughout the 1960s and 1980s in several regions of Africa, and it is suggested that the virus spread to Asia as several outbreaks arose concurrently (Powers, et al, 2000, p. 471). In the 2000s, cases have been reported in various other regions including Europe, North America, and Australia (Powers & Logue, 2007, p. 2365. Recently, large epidemics in India have caused concern about the growing rate of incidence (Pialoux, Gauzere, Jauréguiberry, & Strobel, 2007, p. 319).…”

Section: Origin and Historymentioning

confidence: 99%

Combating Bioterrorism: Purification and Structural Analysis of the E3 Proteins of the Venezuelan Equine Encephalitis Virus and the Chikungunya Virus

Gwin¹

2011

JPUR

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Outbreaks of the Venezuelan Equine Encephalitis Virus (VEEV) and the Chikungunya Virus (CHIKV) continue to emerge in Central and South America, Africa, and Asia, but there are currently no vaccines or anti-virals for these viruses. Given their ease of transmission, debilitating symptoms, and genetic alterability, VEEV and CHIKV have great potential for development into biological weapons. Therefore, there is an urgent need to determine possible methods of treatment or prevention. One possibility of prevention lies in determining the structure and biological function of the E3 protein that plays a key role in the infectivity of the viruses. In this research, heavy nitrogen (N 15 ) labeling and nickelaffinity purification were used to purify E3 from VEEV. The labeled E3 was used in nuclear magnetic resonance (NMR) to determine secondary structure, but protein aggregation resulted in poor signal. Although various purification techniques, including cobalt-affinity purification, were used to obtain small amounts of E3 protein from CHIKV, further work is needed in order to obtain enough protein to be used for NMR analysis.

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Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus

Cited by 673 publications

References 84 publications

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

A Mouse Model of Chikungunya Virus–Induced Musculoskeletal Inflammatory Disease

Combating Bioterrorism: Purification and Structural Analysis of the E3 Proteins of the Venezuelan Equine Encephalitis Virus and the Chikungunya Virus

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