Inositol Phosphates and Retroviral Assembly: A Cellular Perspective

Ricana, C.L.; Dick, Robert A.

doi:10.3390/v13122516

Cited by 5 publications

(4 citation statements)

References 132 publications

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“…IP 6 interacts with the six-helix bundle structure and stabilizes the immature Gag lattice. IP 6 is also very crucial for the assembly of CA into the mature fullerene-like cone lattice [187][188][189][190][191][192].…”

Section: Maturation Inhibitorsmentioning

confidence: 99%

A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication

Sever,

Otsuka,

Fujita

et al. 2024

IJMS

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Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, the multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for the discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body’s health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from patients’ bodies. A potential strategy called “lock-in and apoptosis” targets the budding phase of the life cycle of the virus and leads to susceptibility to apoptosis of HIV-1 infected cells for the elimination of HIV-1 reservoirs and, ultimately, for complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA)-approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.

show abstract

Section: Maturation Inhibitorsmentioning

confidence: 99%

A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication

Sever,

Otsuka,

Fujita

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…IP6 interacts with the six-helix bundle structure and stabilizes the immature Gag lattice. IP6 is also very crucial for assembly of CA into the mature fullerene-like cone lattice [187][188][189][190][191][192].…”

Section: Maturation Inhibitorsmentioning

confidence: 99%

A Review on FDA Approved Anti-HIV-1 Drugs, Anti-Gag Compounds and Potential Strategies for HIV-1 Eradication

Sever,

Otsuka,

Fujita

et al. 2024

Preprint

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Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from the patients’ bodies. A potential strategy called “lock-in apoptosis” targeting the budding phase of life cycle of virus leading to susceptibility to apoptosis of HIV-1 infected cells for elimination of HIV-1 reservoirs and ultimately for a complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA) approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.

show abstract

“…IP6 was reported to interact with both the MA and CA domains of Gag. IP6 is released by the proteolytic cleavage of Gag and then stabilizes the mature capsid lattice in the course of maturation [ 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. Our research group previously demonstrated that IP6 was able to bind to the MA approximately 10 times more strongly than IP3 [ 38 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of New L-Heptanoylphosphatidyl Inositol Pentakisphosphate Derivatives Targeting the Interaction with HIV-1 Gag by Molecular Modelling Studies

et al. 2022

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The HIV-1 Gag protein binds to the host cell membrane and assembles into immature particles. Then, in the course of immature virion budding, activated protease cleaves Gag into its main components: MA, CA, NC, and p6 proteins. The highly basic residues of MA predominantly interact with the acidic head of phosphatidyl-inositol-4,5-bisphosphate (PI(4,5)P2) inserted into the membrane. Our research group developed L-Heptanoylphosphatidyl Inositol Pentakisphosphate (L-HIPPO) and previously confirmed that this compound bound to the MA more strongly than PI(4,5)P2 and inositol hexakisphosphate (IP6) did. Therefore, herein we rationally designed eight new L-HIPPO derivatives based on the fact that the most changeable parts of L-HIPPO were two acyl chains. After that, we employed molecular docking for eight compounds via Maestro software using high-resolution crystal structures of MA in complex with IP6 (PDB IDs: 7E1I, 7E1J, and 7E1K), which were recently elucidated by our research group. The most promising docking scores were obtained with benzene-inserted compounds. Thus, we generated a library containing 213 new aromatic group-inserted L-HIPPO derivatives and performed the same molecular docking procedure. According to the results, we determined the nine new L-HIPPO derivatives most effectively binding to the MA with the most favorable scoring functions and pharmacokinetic properties for further exploration.

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Inositol Phosphates and Retroviral Assembly: A Cellular Perspective

Cited by 5 publications

References 132 publications

A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication

A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication

A Review on FDA Approved Anti-HIV-1 Drugs, Anti-Gag Compounds and Potential Strategies for HIV-1 Eradication

Identification of New L-Heptanoylphosphatidyl Inositol Pentakisphosphate Derivatives Targeting the Interaction with HIV-1 Gag by Molecular Modelling Studies

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