当前位置： SCI文献检索 > ANTIVIRAL RESEARCH期刊下所有文献 > HIV proteinase inhibitors containing 2-aminobenzylstatine as a novel scissile bond replacement: biochemical and pharmacological characterization.

HIV proteinase inhibitors containing 2-aminobenzylstatine as a novel scissile bond replacement: biochemical and pharmacological characterization.

Abstract：

:Derivation of the 2-aminobenzylstatine containing HIV-1 proteinase (PR) inhibitor I led to a series of compounds with considerably improved antiviral activity, the most potent derivatives inhibiting HIV-1 with IC50 values below 25 nM. This was achieved by the combination of several structural modifications, most prominently by introduction of a benzimidazole heterocycle into the inhibitor. The mode of action of the 2-aminobenzylstatine PR inhibitors was demonstrated to be inhibition of gag precursor processing. The antiviral efficacy of the PR inhibitors was demonstrated in various cell lines, in primary T4 lymphocytes and in monocytes. The most potent compound (XI) inhibited replication of several HIV-1 clinical isolates in primary cells with IC50 values of 8 to 23 nM. The analysis of the pharmacokinetic behaviour of compounds I and VII revealed blood half-lives in rodents in the range of about 1.5 h. Compound I also showed appreciable oral uptake in mice (18%), but yielded no detectable blood levels in rats after oral administration. Benzimidazole containing compounds like VII were not orally bioavailable to a significant extent, neither in mice nor in rats. Thus, while introduction of a benzimidazole group into the PR inhibitors was a successful structural modification with regard to antiviral activity in cell culture, it completely abolished oral bioavailability.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Billich A,Charpiot B,Fricker G,Gstach H,Lehr P,Peichl P,Scholz D,Rosenwirth B

doi

10.1016/0166-3542(94)90005-1

subject

Has Abstract

pub_date

1994-12-01 00:00:00

pages

215-33

issue

3-4

eissn

0166-3542

issn

1872-9096

pii

0166-3542(94)90005-1

journal_volume

25

pub_type

杂志文章

相关文献

ANTIVIRAL RESEARCH文献大全
  • Polymerases of hepatitis C viruses and flaviviruses: structural and mechanistic insights and drug development.

    abstract：:The family Flaviviridae comprises several major human pathogens including hepatitis C virus (genus hepacivirus), yellow fever virus, West Nile virus and dengue virus (genus flavivirus). Flaviviridae genomes comprise a single-stranded RNA segment encoding a single polyprotein that is subsequently processed into 10 matu...

    journal_title：Antiviral research

    pub_type： 杂志文章,评审

    doi：10.1016/j.antiviral.2014.02.006

    authors： Caillet-Saguy C,Lim SP,Shi PY,Lescar J,Bressanelli S

    更新日期：2014-05-01 00:00:00

  • Novel screening systems for HIV-1 fusion mediated by two extra-virion heptad repeats of gp41.

    abstract：:Entry of human immunodeficiency virus type 1 (HIV-1) into target cells is mediated by its envelope protein gp41 through membrane fusion. Interaction of two extra-virion heptad repeats (HRs) in the gp41 plays a pivotal role in the fusion, and its inhibitor, enfuvirtide (T-20), blocks HIV-1 entry. To identify agents tha...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2008.05.006

    authors： Nishikawa H,Kodama E,Sakakibara A,Fukudome A,Izumi K,Oishi S,Fujii N,Matsuoka M

    更新日期：2008-10-01 00:00:00

  • Antiviral activities of lactoferrin.

    abstract：:Lactoferrin (LF) is an iron binding glycoprotein that is present in several mucosal secretions. Many biological functions have been ascribed to LF. One of the functions of LF is the transport of metals, but LF is also an important component of the non-specific immune system, since LF has antimicrobial properties again...

    journal_title：Antiviral research

    pub_type： 杂志文章,评审

    doi：10.1016/s0166-3542(01)00195-4

    authors： van der Strate BW,Beljaars L,Molema G,Harmsen MC,Meijer DK

    更新日期：2001-12-01 00:00:00

  • High-throughput screening for negative-stranded hemorrhagic fever viruses using reverse genetics.

    abstract：:Viral hemorrhagic fevers (VHFs) cause thousands of fatalities every year, but the treatment options for their management remain very limited. In particular, the development of therapeutic interventions is restricted by the lack of commercial viability of drugs targeting individual VHF agents. This makes approaches lik...

    journal_title：Antiviral research

    pub_type： 杂志文章,评审

    doi：10.1016/j.antiviral.2019.104569

    authors： Wendt L,Bostedt L,Hoenen T,Groseth A

    更新日期：2019-10-01 00:00:00

  • Germacrone inhibits early stages of influenza virus infection.

    abstract：:Highly pathogenic influenza viruses pose a serious public health threat to humans. Although vaccines are available, antivirals are needed to efficiently control disease progression and virus transmission due to the emergence of drug-resistant viral strains. In this study, germacrone, which is a major component of the ...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2013.09.021

    authors： Liao Q,Qian Z,Liu R,An L,Chen X

    更新日期：2013-12-01 00:00:00

  • The cumulative occurrence of resistance mutations in the HIV-1 protease gene is associated with failure of salvage therapy with ritonavir and saquinavir in protease inhibitor-experienced patients.

    abstract：:Salvage therapy with ritonavir (RTV) and saquinavir (SQV) failed to achieve virological and immunological improvement in 24 HIV-infected patients who discontinued triple therapy with RTV or indinavir (IDV) because of failure or intolerance to treatment. Changes in the HIV-1 protease gene sequence were analyzed prospec...

    journal_title：Antiviral research

    pub_type： 临床试验,杂志文章

    doi：10.1016/s0166-3542(00)00110-8

    authors： Karmochkine M,Si Mohamed A,Piketty C,Ginsburg C,Raguin G,Schneider-Fauveau V,Gutmann L,Kazatchkine MD,Belec L

    更新日期：2000-09-01 00:00:00

  • Short peptide nucleic acids (PNA) inhibit hepatitis C virus internal ribosome entry site (IRES) dependent translation in vitro.

    abstract：:The internal ribosome entry site (IRES) of hepatitis C virus (HCV) which governs the initiation of protein synthesis from viral RNA represents an ideal target for antisense approaches. Using an original bicistronic plasmid, we first established that sequence and translational activity of HCV IRESs cloned from six pati...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2008.06.011

    authors： Alotte C,Martin A,Caldarelli SA,Di Giorgio A,Condom R,Zoulim F,Durantel D,Hantz O

    更新日期：2008-12-01 00:00:00

  • Modeling HCV cure after an ultra-short duration of therapy with direct acting agents.

    abstract：BACKGROUND:Cases of sustained-virological response (SVR or cure) after an ultra-short duration (≤27 days) of direct-acting antiviral (DAA)-based therapy, despite HCV being detected at end of treatment (EOT), have been reported. Established HCV mathematical models that predict the treatment duration required to achieve ...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2017.06.019

    authors： Goyal A,Lurie Y,Meissner EG,Major M,Sansone N,Uprichard SL,Cotler SJ,Dahari H

    更新日期：2017-08-01 00:00:00

  • Synthetic RNAi triggers and their use in chronic hepatitis B therapies with curative intent.

    abstract：:Current therapies for chronic hepatitis B virus infection (CHB) - nucleos(t)ide analogue reverse transcriptase inhibitors and interferons - result in low rates of functional cure defined as sustained off-therapy seroclearance of hepatitis B surface antigen (HBsAg). One likely reason is the inability of these therapies...

    journal_title：Antiviral research

    pub_type： 杂志文章,评审

    doi：10.1016/j.antiviral.2015.06.019

    authors： Gish RG,Yuen MF,Chan HL,Given BD,Lai CL,Locarnini SA,Lau JY,Wooddell CI,Schluep T,Lewis DL

    更新日期：2015-09-01 00:00:00

  • A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.

    abstract：:The mammarenavirus Lassa (LASV) is highly prevalent in West Africa where it infects several hundred thousand individuals annually resulting in a high number of Lassa fever (LF) cases, a febrile disease associated with high morbidity and significant mortality. Mounting evidence indicates that the worldwide-distributed ...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2019.104667

    authors： Cubitt B,Ortiz-Riano E,Cheng BY,Kim YJ,Yeh CD,Chen CZ,Southall NOE,Zheng W,Martinez-Sobrido L,de la Torre JC

    更新日期：2020-01-01 00:00:00

  • Animal models of Middle East respiratory syndrome coronavirus infection.

    abstract：:The emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second time that a new, highly pathogenic coronavirus has emerged in the human population in the 21st century. In this review, we discuss the current state of knowledge of animal models of MERS-CoV infection. Commonly used ...

    journal_title：Antiviral research

    pub_type： 杂志文章,评审

    doi：10.1016/j.antiviral.2015.07.005

    authors： van Doremalen N,Munster VJ

    更新日期：2015-10-01 00:00:00

  • Potent and broad-spectrum cycloheptathiophene-3-carboxamide compounds that target the PA-PB1 interaction of influenza virus RNA polymerase and possess a high barrier to drug resistance.

    abstract：:Influenza viruses are major respiratory pathogens responsible for both seasonal epidemics and occasional pandemics worldwide. The current available treatment options have limited efficacy and thus the development of new antivirals is highly needed. We previously reported the identification of a series of cycloheptathi...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2019.03.003

    authors： Nannetti G,Massari S,Mercorelli B,Bertagnin C,Desantis J,Palù G,Tabarrini O,Loregian A

    更新日期：2019-05-01 00:00:00

  • Rift Valley fever virus: Unanswered questions.

    abstract：:This mosquito-borne pathogen of humans and animals respects no international or geographic boundaries. It is currently found in parts of Africa and the Arabian Peninsula where periodic outbreaks of severe and fatal disease occur, and threatens to spread into other geographic regions. In recent years, modern molecular ...

    journal_title：Antiviral research

    pub_type： 杂志文章,评审

    doi：10.1016/j.antiviral.2016.07.005

    authors： Bird BH,McElroy AK

    更新日期：2016-08-01 00:00:00

  • A sugar binding protein cyanovirin-N blocks herpes simplex virus type-1 entry and cell fusion.

    abstract：:Herpes simplex virus type-1 (HSV-1) causes significant health problems from periodic skin and corneal lesions to encephalitis. It is also considered a cofactor in the development of age-related secondary glaucoma. Inhibition of HSV-1 at the stage of viral entry generates a unique opportunity for preventative and/or th...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2009.07.014

    authors： Tiwari V,Shukla SY,Shukla D

    更新日期：2009-10-01 00:00:00

  • The ReFRAME library as a comprehensive drug repurposing library to identify mammarenavirus inhibitors.

    abstract：:Several mammarenaviruses, chiefly Lassa virus (LASV) in Western Africa and Junín virus (JUNV) in the Argentine Pampas, cause severe disease in humans and pose important public health problems in their endemic regions. Moreover, mounting evidence indicates that the worldwide-distributed mammarenavirus lymphocytic chori...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2019.104558

    authors： Kim YJ,Cubitt B,Chen E,Hull MV,Chatterjee AK,Cai Y,Kuhn JH,de la Torre JC

    更新日期：2019-09-01 00:00:00

  • Orthopoxvirus targets for the development of new antiviral agents.

    abstract：:Investments in the development of new drugs for orthopoxvirus infections have fostered new avenues of research, provided an improved understanding of orthopoxvirus biology and yielded new therapies that are currently progressing through clinical trials. These broad-based efforts have also resulted in the identificatio...

    journal_title：Antiviral research

    pub_type： 杂志文章,评审

    doi：10.1016/j.antiviral.2012.02.012

    authors： Prichard MN,Kern ER

    更新日期：2012-05-01 00:00:00

  • Natural killer cell inhibits human immunodeficiency virus replication in chronically infected immune cells.

    abstract：:Natural killer (NK) cells are a crucial component of the host innate immune system. We investigated the noncytolytic anti-human immunodeficiency virus (HIV) activity of NK cells in chronically HIV-infected immune cells. Supernatants collected from NK cell cultures (both primary NK cells and NK cell lines, YTS and NK 9...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2006.08.006

    authors： Zhang T,Li Y,Wang YJ,Wang X,Young M,Douglas SD,Ho WZ

    更新日期：2007-02-01 00:00:00

  • Resistance associated mutations to dolutegravir (S/GSK1349572) in HIV-infected patients--impact of HIV subtypes and prior raltegravir experience.

    abstract：:Dolutegravir (S/GSK1349572) is a second-generation HIV-1 integrase inhibitor (INI) in advanced clinical development. It has shown good antiviral activity in most patients with prior raltegravir failure, although changes at the integrase codon 148, particularly when combined with other mutations, confer reduced suscept...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2011.03.178

    authors： Garrido C,Soriano V,Geretti AM,Zahonero N,Garcia S,Booth C,Gutierrez F,Viciana I,de Mendoza C

    更新日期：2011-06-01 00:00:00

  • Lack of effect of bovine lactoferrin in respiratory syncytial virus replication and clinical disease severity in the mouse model.

    abstract：BACKGROUND:Lactoferrin (LF) is a glycoprotein present in human milk with known antimicrobial effects. In vitro, LF has demonstrated antiviral activity against respiratory syncytial virus (RSV). We sought to assess the effect of bovine (b)LF in RSV replication, lung inflammation and function, cytokine profiles and clini...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2013.05.013

    authors： Gualdi L,Mertz S,Gomez AM,Ramilo O,Wittke A,Mejias A

    更新日期：2013-08-01 00:00:00

  • Protocatechuic aldehyde inhibits hepatitis B virus replication both in vitro and in vivo.

    abstract：:Natural compounds provide a large reservoir of potentially active anti-hepatitis B virus (HBV) agents. We examined the direct effects of protocatechuic aldehyde (PA; derived from the Chinese herb, Salvia miltiorrhiza) on HBV replication in HepG2 2.2.15 cell line and duck hepatitis B virus (DHBV) replication in ducklin...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2006.12.005

    authors： Zhou Z,Zhang Y,Ding XR,Chen SH,Yang J,Wang XJ,Jia GL,Chen HS,Bo XC,Wang SQ

    更新日期：2007-04-01 00:00:00

  • Treatment of herpes simplex virus infections.

    abstract：:Herpes simplex virus (HSV) types 1 and 2 are ubiquitous organisms that cause infections in human populations throughout the world. The clinical manifestations of HSV infections are varied, ranging from asymptomatic disease to life-threatening illness in neonates and immunocompromised hosts. This article will review th...

    journal_title：Antiviral research

    pub_type： 杂志文章,评审

    doi：10.1016/j.antiviral.2003.09.006

    authors： Brady RC,Bernstein DI

    更新日期：2004-02-01 00:00:00

  • Effect of protease inhibitors on HIV-1 maturation and infectivity.

    abstract：:The effects of HIV-1 protease inhibitors on proteolytic processing and infectivity of virions produced from lymphocytes chronically infected with the virus were studied. Protease inhibition was detected by the accumulation of the polyprotein precursors Pr55gag and Pr160gag-pol and their cleavage intermediates. Immunob...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/s0166-3542(99)00074-1

    authors： Jardine DK,Tyssen DP,Birch CJ

    更新日期：2000-01-01 00:00:00

  • Structural biology of dengue virus enzymes: towards rational design of therapeutics.

    abstract：:Development of anti-dengue therapy represents an urgent un-met medical need. Towards antiviral therapy, recent advances in crystal structures of DENV enzymes have led to the possibility of structure-based rational design of inhibitors for anti-dengue therapy. These include (i) the structure of the 'active' form of the...

    journal_title：Antiviral research

    pub_type： 杂志文章,评审

    doi：10.1016/j.antiviral.2012.09.007

    authors： Noble CG,Shi PY

    更新日期：2012-11-01 00:00:00

  • Conditionally replicating lentiviral-hybrid episomal vectors for suicide gene therapy.

    abstract：:Lentiviral vectors have been shown to be good candidates for gene transfer protocols; however, prevention of insertional mutagenesis remains problematic. Here we report on the design of a conditionally replicating integrase (IN)-defective lentiviral-hybrid episomal vector in which the insertion of the SV40 promoter/or...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2008.06.015

    authors： Vargas J Jr,Klotman ME,Cara A

    更新日期：2008-12-01 00:00:00

  • Toxicity and antiviral activity of LY253963 against respiratory syncytial and parainfluenza type 3 viruses in tissue culture and in cotton rats.

    abstract：:LY253963, the sodium salt of 1,3,4-thiadiazol-2-ylcyanamide, was evaluated in tissue culture and in cotton rats for toxicity and antiviral efficacy against respiratory syncytial (RSV) and parainfluenza type 3 (PIV3) viruses. The selective index (ratio of the median toxic dose: median efficacious dose) of LY253963 in H...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/0166-3542(90)90005-r

    authors： Wyde PR,Ambrose MW,Meyer HL,Gilbert BE

    更新日期：1990-10-01 00:00:00

  • Antiviral drug susceptibility assays: going with the flow.

    abstract：:This review describes the procedures for the use of fluorochrome labeled monoclonal antibodies and flow cytometry for the detection and quantification of virus infected cells. The application of this technology for (1) identifying virus infected cells in clinical specimens obtained from human cytomegalovirus (HCMV) an...

    journal_title：Antiviral research

    pub_type： 杂志文章,评审

    doi：10.1016/s0166-3542(99)00039-x

    authors： McSharry JJ

    更新日期：1999-08-01 00:00:00

  • Molecular basis of antagonism between K70E and K65R tenofovir-associated mutations in HIV-1 reverse transcriptase.

    abstract：:The K70E mutation in HIV-1 reverse transcriptase was observed in 10% of virologic non-responders of the abacavir/lamivudine/tenofovir arm of ESS30009, alone, or in mixtures with K65R by population sequencing. Clonal analysis of six ESS30009 K70E isolates failed to identify double mutants carrying K65R+K70E. Site-direc...

    journal_title：Antiviral research

    pub_type： 杂志文章,随机对照试验

    doi：10.1016/j.antiviral.2007.03.006

    authors： Kagan RM,Lee TS,Ross L,Lloyd RM Jr,Lewinski MA,Potts SJ

    更新日期：2007-09-01 00:00:00

  • Phenotypic and genotypic characterization of acyclovir-resistant clinical isolates of herpes simplex virus.

    abstract：:Sixteen herpes simplex virus type 1 (HSV-1) and four type 2 (HSV-2) isolates resistant to acyclovir (ACV) were characterized retrospectively for drug resistance. Phenotypic testing was performed by means of tetrazolium reduction assay and genotypic analysis was carried out by sequencing of thymidine kinase (TK) and DN...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2010.03.002

    authors： Sauerbrei A,Deinhardt S,Zell R,Wutzler P

    更新日期：2010-06-01 00:00:00

  • Reverse genetics approaches to combat pathogenic arenaviruses.

    abstract：:Several arenaviruses cause hemorrhagic fever (HF) in humans, and evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. Moreover, arenaviruses pose a biodefense threat. No licensed anti-arenavirus vaccine...

    journal_title：Antiviral research

    pub_type： 杂志文章,评审

    doi：10.1016/j.antiviral.2008.08.002

    authors： de la Torre JC

    更新日期：2008-12-01 00:00:00

  • Adefovir dipivoxil efficiently inhibits the proliferation of pseudorabies virus in vitro and in vivo.

    abstract：:Since 2011, highly pathogenic pseudorabies virus (PRV) variants that emerged on many farms in China have posed major economic burdens to the animal industry and have even recently caused several human cases of viral encephalitis. Currently, there are no approved effective drugs to treat PRV associated diseases in huma...

    journal_title：Antiviral research

    pub_type： 杂志文章

    doi：10.1016/j.antiviral.2021.105014

    authors： Wang G,Chen R,Huang P,Hong J,Cao J,Wu Q,Zheng W,Lin L,Han Q,Chen Y,Xia N

    更新日期：2021-01-07 00:00:00