Antiviral Chemistry and Chemotherapy最新文献_第6页

Corrigendum. 勘误表。

Antiviral Chemistry and Chemotherapy Pub Date : 2018-01-01 DOI: 10.1177/2040206618790862

引用次数: 0

Addressing the selectivity and toxicity of antiviral nucleosides. 解决抗病毒核苷的选择性和毒性。

Antiviral Chemistry and Chemotherapy Pub Date : 2018-01-01 DOI: 10.1177/2040206618758524

Joy Y Feng

引用次数: 39

Nucleosides for the treatment of respiratory RNA virus infections. 治疗呼吸道 RNA 病毒感染的核苷类药物。

Antiviral Chemistry and Chemotherapy Pub Date : 2018-01-01 DOI: 10.1177/2040206618764483

Paul C Jordan, Sarah K Stevens, Jerome Deval

{"title":"Nucleosides for the treatment of respiratory RNA virus infections.","authors":"Paul C Jordan, Sarah K Stevens, Jerome Deval","doi":"10.1177/2040206618764483","DOIUrl":"10.1177/2040206618764483","url":null,"abstract":"Influenza virus, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, coronaviruses, and rhinoviruses are among the most common viruses causing mild seasonal colds. These RNA viruses can also cause lower respiratory tract infections leading to bronchiolitis and pneumonia. Young children, the elderly, and patients with compromised cardiac, pulmonary, or immune systems are at greatest risk for serious disease associated with these RNA virus respiratory infections. In addition, swine and avian influenza viruses, together with severe acute respiratory syndrome-associated and Middle Eastern respiratory syndrome coronaviruses, represent significant pandemic threats to the general population. In this review, we describe the current medical need resulting from respiratory infections caused by RNA viruses, which justifies drug discovery efforts to identify new therapeutic agents. The RNA polymerase of respiratory viruses represents an attractive target for nucleoside and nucleotide analogs acting as inhibitors of RNA chain synthesis. Here, we present the molecular, biochemical, and structural fundamentals of the polymerase of the four major families of RNA respiratory viruses: Orthomyxoviridae, Pneumoviridae/Paramyxoviridae, Coronaviridae, and Picornaviridae. We summarize past and current efforts to develop nucleoside and nucleotide analogs as antiviral agents against respiratory virus infections. This includes molecules with very broad antiviral spectrum such as ribavirin and T-705 (favipiravir), and others targeting more specifically one or a few virus families. Recent advances in our understanding of the structure(s) and function(s) of respiratory virus polymerases will likely support the discovery and development of novel nucleoside analogs.","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"26 ","pages":"2040206618764483"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/64/10.1177_2040206618764483.PMC5890544.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35933515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in antiviral nucleoside analogues and their prodrugs. 抗病毒核苷类似物及其前药研究进展。

Antiviral Chemistry and Chemotherapy Pub Date : 2018-01-01 DOI: 10.1177/2040206618781410

Katherine Seley-Radtke, Jerome Deval

引用次数: 2

Flexibility-Not just for yoga anymore! 灵活性——不再是瑜伽的专利!

Antiviral Chemistry and Chemotherapy Pub Date : 2018-01-01 DOI: 10.1177/2040206618756788

Katherine Seley-Radtke

引用次数: 7

Investigation of the solvent-dependent photolysis of a nonnucleoside reverse-transcriptase inhibitor, antiviral agent efavirenz. 非核苷类逆转录酶抑制剂、抗病毒药物依非韦伦的溶剂依赖性光解研究。

Antiviral Chemistry and Chemotherapy Pub Date : 2017-12-01 Epub Date: 2017-09-11 DOI: 10.1177/2040206617730170

Maryam A Jordaan, Michael Shapi

{"title":"Investigation of the solvent-dependent photolysis of a nonnucleoside reverse-transcriptase inhibitor, antiviral agent efavirenz.","authors":"Maryam A Jordaan, Michael Shapi","doi":"10.1177/2040206617730170","DOIUrl":"https://doi.org/10.1177/2040206617730170","url":null,"abstract":"This study sought to investigate the solvent-dependency on the photolysis of efavirenz to gain insight into the photoprocesses involved. The primary mechanisms were firstly the excited-state intramolecular proton transfer (i.e. phototautomerization), which generated the imidic acid phototautomer observed as [M-H]- quasimolecular ion at m/z 314.0070 in the high-performance liquid chromatography-electrospray ionization-time-of-flight mass spectrometry in the negative mode. Secondly, the photoinduced α-cleavage with the loss of a carbonyl group occurred (i.e. photodecarbonylation) to form the photoproduct at m/z 286.0395. The ultraviolet-visible spectra illustrated a large, hyperchromic, and slight bathochromic effect in both the π→π* and n→π* electronic transitions. The largest bathochromic effect was prevalent in the chloroform solvent, i.e. chloroform (π* = 0.58; β = 0.00; α = 0.44) > methanol (π* = 0.60; β = 0.66; α = 0.98) > acetonitrile (π* = 0.75; β = 0.40; α = 0.19). This is due to the significant interaction of the amino group with the excited carbonyl moiety which is attributed to intramolecular phototautomerization resulting in a larger energy shift of the electronic state. A plausible explanation is due to the hydrogen bond donor ability of the polar methanol and nonpolar chloroform solvents, which stabilized the polarized imidic acid phototautomer by means of hydrogen bonding interactions, as opposed to the aprotic acetonitrile which exhibits no hydrogen bonding interactions. The study would form the basis for further photolytic analyses and syntheses to generate a plethora of novel photoproducts with anti-HIV activity based on the biologically active benzoxazinone framework of efavirenz.","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"25 3","pages":"94-104"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206617730170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35395691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Establishment of an antiviral assay system and identification of severe fever with thrombocytopenia syndrome virus inhibitors. 建立抗病毒检测系统和鉴定重症发热伴血小板减少综合征病毒抑制剂。

Antiviral Chemistry and Chemotherapy Pub Date : 2017-12-01 Epub Date: 2017-11-03 DOI: 10.1177/2040206617740303

Masanori Baba, Masaaki Toyama, Norikazu Sakakibara, Mika Okamoto, Naomichi Arima, Masayuki Saijo

{"title":"Establishment of an antiviral assay system and identification of severe fever with thrombocytopenia syndrome virus inhibitors.","authors":"Masanori Baba, Masaaki Toyama, Norikazu Sakakibara, Mika Okamoto, Naomichi Arima, Masayuki Saijo","doi":"10.1177/2040206617740303","DOIUrl":"https://doi.org/10.1177/2040206617740303","url":null,"abstract":"Aims Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease. SFTS is epidemic in Asia, and its fatality rate is around 30% in Japan. The causative virus severe fever with thrombocytopenia syndrome virus (SFTSV) is a phlebovirus of the family Phenuiviridae (the order Bunyavirales). Although effective treatments are required, there are no antiviral agents currently approved for clinical use. Ribavirin and favipiravir were examined for their anti-SFTSV activity and found to be selective inhibitors of SFTSV replication in vitro. However, their activity was not sufficient. Therefore, it is mandatory to identify novel compounds active against SFTSV. To this end, we have established a safe and rapid assay system for screening selective inhibitors of SFTSV. Methods The virus was isolated from SFTS patients treated in Kagoshima University Hospital. Vero cells were infected with SFTSV and incubated in the presence of various concentrations of test compounds. After three days, the cells were examined for their intracellular viral RNA levels by real-time reverse transcription-PCR without extracting viral RNA. The cytotoxicity of test compounds was determined by a tetrazolium dye method. Results Among the test compounds, the antimalarial agent amodiaquine was identified as a selective inhibitor of SFTSV replication. Its 50% effective concentration (EC50) and cytotoxic concentration (CC50) were 19.1 ± 5.1 and >100 µM, respectively. The EC50 value of amodiaquine was comparable to those of ribavirin and favipiravir. Conclusion Amodiaquine is considered to be a promising lead of novel anti-SFTSV agents, and evaluating the anti-SFTSV activity of its derivatives is in progress.","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"25 3","pages":"83-89"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206617740303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35516629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 24

3,7-Dideazaneplanocin: Synthesis and antiviral analysis. 3,7-二氮唑奈planocin:合成及抗病毒分析。

Antiviral Chemistry and Chemotherapy Pub Date : 2017-12-01 DOI: 10.1177/2040206617742561

Xue-Qiang Yin, Stewart W Schneller

{"title":"3,7-Dideazaneplanocin: Synthesis and antiviral analysis.","authors":"Xue-Qiang Yin, Stewart W Schneller","doi":"10.1177/2040206617742561","DOIUrl":"https://doi.org/10.1177/2040206617742561","url":null,"abstract":"Objective To synthesize 3,7-dideazaneplanocin and evaluate its antiviral potential. Methods The target 3,7-dideazaneplanocin has been prepared in five steps from a readily available cyclopentenol. A thorough in vitro antiviral analysis was conducted versus both DNA and RNA viruses. Results A rational synthesis of 3,7-dideazaneplanocin was conceived and successfully pursued in such a way that it can be adapted to various analogs of 3,7-dideazaneplanocin. Using standard antiviral assays, no activity for 3,7-dideazaneplanocn was found. Conclusion Two structural features are necessary for adenine-based carbocyclic nucleosides (like neplanocin) for potential antiviral properties: (i) inhibition of S-adenosylhomocysteine hydrolase and/or (ii) C-5' activation via the mono-nucleotide. These two requisite adenine structural features to fit these criteria are not present in in the target 3,7-dideazaneplanocin: (i) an N-7 is necessary for inhibition of the hydrolase and the N-3 is claimed to be essential for phosphorylation at C-5'. Thus, it is not surprising that 3,7-dideazaneplaoncin lacked antiviral properties.","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"25 3","pages":"90-93"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206617742561","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35281652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Nucleoside diphosphate and triphosphate prodrugs - An unsolvable task? 核苷二磷酸和三磷酸原药--无法解决的难题？

Antiviral Chemistry and Chemotherapy Pub Date : 2017-12-01 Epub Date: 2017-11-03 DOI: 10.1177/2040206617738656

Chris Meier

{"title":"Nucleoside diphosphate and triphosphate prodrugs - An unsolvable task?","authors":"Chris Meier","doi":"10.1177/2040206617738656","DOIUrl":"10.1177/2040206617738656","url":null,"abstract":"In this review, our recent advances in the development of nucleoside di- and nucleoside triphosphate prodrugs is summarized. Previously, we had developed a successful membrane-permeable pronucleotide system for the intracellular delivery of nucleoside monophosphates as well, the so-called cycloSal-approach. In contrast to that work in which the delivery is initiated by a chemically driven hydrolysis reaction, for the di- and triphosphate delivery, an enzymatic trigger mechanism involving (carboxy)esterases had to be used. The other features of the new pronucleotide approaches are: (i) lipophilic modification was restricted to the terminal phosphate group leaving charges at the internal phosphate moieties and (ii) appropriate lipophilicity is introduced by long aliphatic residues within the bipartite prodrug moiety. The conceptional design of the di- and triphosphate prodrug systems will be described and the chemical synthesis, the hydrolysis properties, a structure-activity relationship and antiviral activity data will be discussed as well. The advantage of these new approaches is that all phosphorylation steps from the nucleoside analogue into the bioactive nucleoside triphosphate form can be bypassed in the case of the triphosphate prodrugs. Moreover, enzymatic processes like the deamination of nucleosides or nucleoside monophosphates which lead to catabolic clearance of the potential antivirally active compound can be avoided by the delivery of the higher phosphorylated nucleotides.","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"25 3","pages":"69-82"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/2f/10.1177_2040206617738656.PMC5890512.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35516628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential of small-molecule fungal metabolites in antiviral chemotherapy. 小分子真菌代谢物在抗病毒化疗中的潜力。

Antiviral Chemistry and Chemotherapy Pub Date : 2017-08-01 Epub Date: 2017-07-23 DOI: 10.1177/2040206617705500

Biswajit G Roy

{"title":"Potential of small-molecule fungal metabolites in antiviral chemotherapy.","authors":"Biswajit G Roy","doi":"10.1177/2040206617705500","DOIUrl":"10.1177/2040206617705500","url":null,"abstract":"Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge. Decades of intense research yielded a handful of natural and synthetic therapeutic options. But emergence of new viruses and drug-resistant viral strains had made new drug development process a never-ending battle. Small-molecule fungal metabolites due to their vast diversity, stereochemical complexity, and preapproved biocompatibility always remain an attractive source for new drug discovery. Though, exploration of therapeutic importance of fungal metabolites has started early with discovery of penicillin, recent prediction asserted that only a small percentage (5-10%) of fungal species have been identified and much less have been scientifically investigated. Therefore, exploration of new fungal metabolites, their bioassay, and subsequent mechanistic study bears huge importance in new drug discovery endeavors. Though no fungal metabolites so far approved for antiviral treatment, many of these exhibited high potential against various viral diseases. This review comprehensively discussed about antiviral activities of fungal metabolites of diverse origin against some important viral diseases. This also highlighted the mechanistic details of inhibition of viral replication along with structure-activity relationship of some common and important classes of fungal metabolites.","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"25 2","pages":"20-52"},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206617705500","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35193844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 32