<scp>HIV</scp>‐1 Entry Inhibitors: A Review of Experimental and Computational Studies

Rad, Tahereh Mostashari; Saghaie, Lotfollah; Fassihi, Afshin

doi:10.1002/cbdv.201800159

Cited by 16 publications

(8 citation statements)

References 74 publications

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“…This is why many of the efforts in basic and clinical research have been aimed at developing strategies to block the virus entry into target cells. Most of the current approaches are based on pharmacological inhibition of the Env proteins, main receptor or co-receptors, as well as the membrane-hemifusion process before viral entry (reviewed in Mostashari Rad et al, 2018). The discovery of LTNP patients (Lambotte et al, 2005) may help to shed some light on identifying cellular mechanisms that are responsible for the control of the disease, not only because of their genetic background but also because of the characteristics of the virus.…”

Section: Discussionmentioning

confidence: 99%

The Interplay of HIV and Autophagy in Early Infection

et al. 2021

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HIV/AIDS is still a global threat despite the notable efforts made by the scientific and health communities to understand viral infection, to design new drugs or to improve existing ones, as well as to develop advanced therapies and vaccine designs for functional cure and viral eradication. The identification and analysis of HIV-1 positive individuals that naturally control viral replication in the absence of antiretroviral treatment has provided clues about cellular processes that could interact with viral proteins and RNA and define subsequent viral replication and clinical progression. This is the case of autophagy, a degradative process that not only maintains cell homeostasis by recycling misfolded/old cellular elements to obtain nutrients, but is also relevant in the innate and adaptive immunity against viruses, such as HIV-1. Several studies suggest that early steps of HIV-1 infection, such as virus binding to CD4 or membrane fusion, allow the virus to modulate autophagy pathways preparing cells to be permissive for viral infection. Confirming this interplay, strategies based on autophagy modulation are able to inhibit early steps of HIV-1 infection. Moreover, autophagy dysregulation in late steps of the HIV-1 replication cycle may promote autophagic cell-death of CD4+ T cells or control of HIV-1 latency, likely contributing to disease progression and HIV persistence in infected individuals. In this scenario, understanding the molecular mechanisms underlying HIV/autophagy interplay may contribute to the development of new strategies to control HIV-1 replication. Therefore, the aim of this review is to summarize the knowledge of the interplay between autophagy and the early events of HIV-1 infection, and how autophagy modulation could impair or benefit HIV-1 infection and persistence, impacting viral pathogenesis, immune control of viral replication, and clinical progression of HIV-1 infected patients.

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Section: Discussionmentioning

confidence: 99%

The Interplay of HIV and Autophagy in Early Infection

et al. 2021

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“…However, considering the −2459G > A status may be important in studies where (a) immunologic strategies, such as antibodies for CCR5 [33], HIV-1 neutralizing antibodies [34,35], and therapeutic HIV-1 vaccines [36], and (b) chemotherapeutic strategies, such as CCR5 antagonists [37][38][39], are evaluated. Here, knowing whether an individual, receiving such an immunologic or chemotherapeutic intervention, is genotypically G/G, G/A, or A/A would enable a better understanding of the response to the intervention, due to a mechanistic or constitutive explanation.…”

mentioning

confidence: 99%

CCR5 Promoter Polymorphism −2459G > A: Forgotten or Ignored?

Mehlotra

2019

Cells

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C-C chemokine receptor 5 (CCR5) polymorphisms, particularly a 32-base pair deletion (∆32) in the open reading frame and −2459G > A in the promoter, are well known for their associations with HIV-1 infection and/or disease progression in a variety of studies. In this era of an HIV cure, where all the emphasis is on ∆32, it seems that −2459G > A has been forgotten or ignored. There is significant importance in the incorporation of the CCR5 −2459G > A genotype information into studies evaluating new immunologic and chemotherapeutic strategies, and those designing and implementing better treatment strategies with current antiretroviral therapy, doing so would enable a better understanding of the response to the intervention, due to a mechanistic or constitutive explanation. Until we find a strategy, whether a stem-cell transplantation or CCR5 editing approach or something else, that delivers a cure to the millions, we should make use of every piece of information that may help curtail HIV/AIDS as a threat to public health.

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“…Entry inhibitors act by preventing HIV from entering into the host cell [ 144 ]. So far, the following entry inhibitors have been approved for HIV treatment and are currently used in clinical practice: (a) Maraviroc (MVC), a C-C chemokine receptor-5 (CCR-5) inhibitor which prevents the interaction of CCR-5 with envelope glycoprotein GP-120 (gp120); (b) Enfuvirtide, a ‘fusion inhibitor’ which binds to the transmembrane glycoprotein GP-41 (gp41) preventing the outer membrane of HIV from fusing to the approximate membrane of T-cells and the subsequent cell entry; (c) Idalizumab which binds to domain 2 of CD4 + T-cells and interferes with the post-attachment steps required for the entry of HIV particles into the host cells; and (d) Fostemsavir, approved by the FDA in 2020, which binds directly to gp120 prohibiting the interaction needed between the virus and the surface receptors on CD4 + T-cells [ 145 , 146 ].…”

Section: Entry Inhibitorsmentioning

confidence: 99%

Liver Fibrosis during Antiretroviral Treatment in HIV-Infected Individuals. Truth or Tale?

Bakasis

Ανδρουτσάκος

2021

Cells

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After the introduction of antiretroviral treatment (ART) back in 1996, the lifespan of people living with HIV (PLWH) has been substantially increased, while the major causes of morbidity and mortality have switched from opportunistic infections and AIDS-related neoplasms to cardiovascular and liver diseases. HIV itself may lead to liver damage and subsequent liver fibrosis (LF) through multiple pathways. Apart from HIV, viral hepatitis, alcoholic and especially non-alcoholic liver diseases have been implicated in liver involvement among PLWH. Another well known cause of hepatotoxicity is ART, raising clinically significant concerns about LF in long-term treatment. In this review we present the existing data and analyze the association of LF with all ART drug classes. Published data derived from many studies are to some extent controversial and therefore remain inconclusive. Among all the antiretroviral drugs, nucleoside reverse transcriptase inhibitors, especially didanosine and zidovudine, seem to carry the greatest risk for LF, with integrase strand transfer inhibitors and entry inhibitors having minimal risk. Surprisingly, even though protease inhibitors often lead to insulin resistance, they do not seem to be associated with a significant risk of LF. In conclusion, most ART drugs are safe in long-term treatment and seldom lead to severe LF when no liver-related co-morbidities exist.

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HIV‐1 Entry Inhibitors: A Review of Experimental and Computational Studies

Cited by 16 publications

References 74 publications

The Interplay of HIV and Autophagy in Early Infection

The Interplay of HIV and Autophagy in Early Infection

CCR5 Promoter Polymorphism −2459G > A: Forgotten or Ignored?

Liver Fibrosis during Antiretroviral Treatment in HIV-Infected Individuals. Truth or Tale?

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