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Enterovirus A71 antivirals:Past,present,and future

Acta Pharmaceutica Sinica B 2022年第4期12卷 1542-1566页

作者： Jun Wang Yanmei Hu Madeleine Zheng Department of Pharmacology and Toxicology College of Pharmacythe University of ArizonaTucsonAZ 85721USA

Enterovirus A71(EV-A71)is a significant human pathogen,especially in children.EV-A71 infection is one of the leading causes of hand,foot,and mouth diseases(HFMD),and can lead to neurological complications such as acute flaccid myelitis(AFM)in severe cases.Although three EV-A71 vaccines are available in China,they are not broadly protective and have reduced efficacy against emerging strains.There is currently no approved antiviral for EV-A71.Significant progress has been made in developing antivirals against EV-A71 by targeting both viral proteins and host factors.However,viral capsid inhibitors and protease inhibitors failed in clinical trials of human rhinovirus infection due to limited efficacy or side effects.This review discusses major discoveries in EV-A71 antiviral development,analyzes the advantages and limitations of each drug target,and highlights the knowledge gaps that need to be addressed to advance the field forward.

关键词： Enterovirus A71 EV-A71 AntiviralsAcute flaccid myelitis Hand Foot and mouth disease(HFMD) picornavirus 2C protein

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Rupintrivir is a promising candidate for treating severe cases of Enterovirus-71 infection

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World Journal of Gastroenterology 2010年第2期16卷 201-209页

作者： Zhang, Xiao-Nan Song, Zhi-Gang Jiang, Ting Shi, Bi-Sheng Hu, Yun-Wen Yuan, Zheng-Hong Shanghai Publ Hlth Clin Ctr Res Unit Shanghai 201508 Peoples R China Fudan Univ Shanghai Med Coll Key Lab Med Mol Virol Shanghai 200032 Peoples R China

AIM:To evaluate the suitability of rupintrivir against Enterovirus 71(EV71)induced severe clinical symptoms using computational methods. METHODS:The structure of EV71 3C protease was predicted by homology modeling.The binding free energies between rupintrivir and EV71 3C and human rhinovirus 3C protease were computed by molecular dynamics and molecular mechanics Poisson-Boltzmann/ surface area and molecular mechanics generalized-born/ surface area methods.EV71 3C fragments obtained from clinical samples collected during May to July 2008 in Shanghai were amplified by reverse-transcription and polymerase chain reaction and sequenced. RESULTS:We observed that rupintrivir had favorable binding affinity with EV71 3C protease(-10.76 kcal/mol). The variability of the 3C protein sequence in isolates of various outbreaks,including those obtained in our hospital from May to July 2008,were also analyzed to validate the conservation of the drug binding pocket. CONCLUSION:Rupintrivir,whose safety profiles had been proved,is an attractive candidate and can be quickly utilized for treating severe EV71 infection.

关键词： Rupintrivir Hand foot and mouth disease Molecular mechanics Poisson-Boltzmann/surface area Molecular mechanics Generalized-Born/surface area Homology modeling picornavirus

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Heat inactivation of foot-and-mouth disease virus,swine vesicular disease virus and classical swine fever virus when air-dried on plastic and glass surfaces

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Biosafety and Health 2021年第4期3卷 217-223页

作者： Thea Kristensen Graham J.Belsham Kirsten Tjørnehøj National Veterinary Institute Technical University of DenmarkLindholmDK-4771 KalvehaveDenmark Department of Veterinary and Animal Sciences University of CopenhagenGrønnegårdsvej 15DK-1870 Frederiksberg CDenmark Department of Virus&Microbiological Special Diagnostics Statens Serum InstitutArtillerivej 5DK-2300 Copenhagen SDenmark

Foot-and-mouth disease virus(FMDV),swine vesicular disease virus(SVDV)and classical swine fever virus(CSFV)all cause important animal diseases.FMDV affects many different cloven-hoofed animals,whereas SVDV and CSFV are restricted to domestic and feral pigs together with wild boar.Europe is normally free of these diseases,but occasionally outbreaks happen,which can cause huge economic losses.Handling of these viruses,in particular FMDV and CSFV,is only allowed within high containment laboratories and stables.Periodically such facilities need to be decommissioned for repair or closing down,which is done by cleaning and chemical disinfection,followed by fumigation due to residual risk from virus on surfaces in inaccessible places.However,building materials in older laboratories or stables that have housed infected animals may not be well-suited for fumigation.Heat treatment is another way of inactivating viruses.In this study,we have determined the survival of infectivity in air-dried virus samples on glass and plastic surfaces incubated at room temperature or heated to 70°C for 1,2,3,5 and 7 days.Each of the tested viruses was inactivated to below the limit of detection after 24 h or 48 h of incubation at 70°C;in contrast,some of these viruses were still infectious after 7 days of incubation at room temperature.This study provides important information that can be used in relation to decontamination of buildings and in risk-assessments.

关键词： Virus survival picornavirus Pestivirus Decontamination Risk-assessment

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EGCG-S Impacts Oxidative Stress and Infection of Enterovirus 69 in Lung Cells

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Advances in Bioscience and Biotechnology 2021年第5期12卷 109-124页

作者： Hager Mohamed Lee H. Lee Sandra D. Adams Department of Biology Montclair State University Montclair NJ USA

Enteroviruses are responsible for emerging diseases which cause diverse symptoms and may result in neurological complications. An antiviral with multiple mechanisms of action can help prevent enterovirus mediated disease despite differences in the pathogenesis between enteroviruses, including the recently identified enterovirus 69 (EV-69) for which pathogenesis is not well understood. This study investigated the efficacy of epigallocatechin-3-gallate stearate (EGCG-S), a modified form of the antioxidant green tea catechin epigallocatechin-3-gallate (EGCG), in inhibiting EV-69 infection of lung fibroblast cells in vitro. Treatment with EGCG-S resulted in moderate protection from EV-69 mediated cytotoxicity as demonstrated by increased metabolic activity as well as maintenance of cell morphology and mitochondrial function. These effects were correlated with reduced hydrogen peroxide production in infected cells following EGCG-S treatment with concentrations less than 100 μM, suggesting a role for inhibition of EV-69 mediated oxidative stress. This study provides insight into characteristics of EV-69 infection as well as the efficacy of EGCG-S mediated inhibition of EV-69 infection.

关键词： ROS Enterovirus 69 picornavirus Green Tea Flavanol Antioxidant Antivi-ral MRC-5 Cells A549 Cells

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