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Clinical data | |
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Trade names | Fuzeon |
AHFS/Drugs.com | Monograph |
MedlinePlus | a603023 |
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Routes of administration | Subcutaneous |
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Pharmacokinetic data | |
Bioavailability | 84.3% (SC) |
Protein binding | 92% |
Metabolism | Liver |
Elimination half-life | 3.8 hours |
Excretion | unknown |
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ECHA InfoCard | 100.169.201 |
Chemical and physical data | |
Formula | C204H301N51O64 |
Molar mass | 4491.945 g·mol−1 |
3D model (JSmol) | |
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Enfuvirtide (INN), sold under the brand name Fuzeon, is an HIV fusion inhibitor, the first of a class of antiretroviral drugs used in combination therapy for the treatment of AIDS/HIV.
Enfuvirtide is indicated for the treatment of HIV-1 infection, in combination therapy with other antiretrovirals, in people where all other treatments have failed. [2]
Common adverse drug reactions (≥1% of patients) associated with enfuvirtide therapy include: injection site reactions (pain, hardening of skin, erythema, nodules, cysts, itch; experienced by nearly all patients, particularly in the first week), peripheral neuropathy, insomnia, depression, cough, dyspnoea, anorexia, arthralgia, infections (including bacterial pneumonia) and/or eosinophilia. Various hypersensitivity reactions occur infrequently (0.1–1% of patients), symptoms of which include rash, fever, nausea, vomiting, chills, rigors, hypotension, elevated hepatic transaminases; and possibly more severe reactions including respiratory distress, glomerulonephritis and/or anaphylaxis – rechallenge is not recommended. [2]
Enfuvirtide works by disrupting the HIV-1 molecular machinery at the final stage of fusion with the target cell, preventing uninfected cells from becoming infected. A biomimetic peptide, enfuvirtide was designed to mimic components of the HIV-1 fusion machinery and displace them, preventing normal fusion. Drugs that disrupt fusion of virus and target cell are termed entry inhibitors or fusion inhibitors.[ citation needed ]
HIV binds to the host CD4+ cell receptor via the viral protein gp120; gp41, a viral transmembrane protein, then undergoes a conformational change that assists in the fusion of the viral membrane to the host cell membrane. Enfuvirtide binds to gp41 preventing the creation of an entry pore for the capsid of the virus, keeping it out of the cell. [3]
Enfuvirtide is also an activator of the chemotactic factor receptor, formyl peptide receptor 1, and thereby activates phagocytes and presumably other cells bearing this receptor (see formyl peptide receptors). [4] The physiological significance of this activation is unknown.[ citation needed ]
Enfuvirtide is considered to be active against HIV-1 only. Low activity against HIV-2 isolates has been demonstrated in vitro . [5]
Variable susceptibility to enfuvirtide has been observed in clinical isolates, with acquired resistance the result of a mutated 10 amino acid motif in viral gp41. Primary resistance, however, has yet to be observed. [6]
Enfuvirtide is a 36-amino acid peptide with the following sequence: [7] [8]
CH3CO-Tyr-Thr-Ser-Leu-Ile-His-Ser-Leu-Ile-Glu-Glu-Ser-Gln-Asn-Gln-Gln-Glu-Lys-Asn-Glu-Gln-Glu-Leu-Leu-Glu-Leu-Asp-Lys-Trp-Ala-Ser-Leu-Trp-Asn-Trp-Phe-NH2 (Ac-YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF-NH2)
Enfuvirtide originated at Duke University, where researchers formed a pharmaceutical company known as Trimeris. Trimeris began development on enfuvirtide in 1996 and initially designated it T-20. In 1999, Trimeris entered into partnership with Hoffmann-La Roche to complete the development of the drug. It was approved by the U.S. Food and Drug Administration (FDA) on March 13, 2003 [9] as the first HIV fusion inhibitor, a new class of antiretroviral drugs. It was approved on the basis of two studies which compared the effect of optimized regimens of antiretroviral medication with and without the addition of enfuvirtide on serum viral load.[ citation needed ]
The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.
This is a list of AIDS-related topics, many of which were originally taken from the public domain U.S. Department of Health Glossary of HIV/AIDS-Related Terms, 4th Edition.
Growth hormone–releasing hormone (GHRH), also known as somatocrinin or by several other names in its endogenous forms and as somatorelin (INN) in its pharmaceutical form, is a releasing hormone of growth hormone (GH). It is a 44-amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus.
Gp41 also known as glycoprotein 41 is a subunit of the envelope protein complex of retroviruses, including human immunodeficiency virus (HIV). Gp41 is a transmembrane protein that contains several sites within its ectodomain that are required for infection of host cells. As a result of its importance in host cell infection, it has also received much attention as a potential target for HIV vaccines.
Entry inhibitors, also known as fusion inhibitors, are a class of antiviral drugs that prevent a virus from entering a cell, for example, by blocking a receptor. Entry inhibitors are used to treat conditions such as HIV and hepatitis D.
Env is a viral gene that encodes the protein forming the viral envelope. The expression of the env gene enables retroviruses to target and attach to specific cell types, and to infiltrate the target cell membrane.
Vicriviroc, previously named SCH 417690 and SCH-D, is a pyrimidine CCR5 entry inhibitor of HIV-1. It was developed by the pharmaceutical company Schering-Plough. Merck decided to not pursue regulatory approval for use in treatment-experienced patients because the drug did not meet primary efficacy endpoints in late stage trials. Clinical trials continue in patients previously untreated for HIV.
Tazarotene-induced gene-1 (TIG1) is a protein which has been implicated as a putative tumor suppressor. It is structurally similar to the protein latexin, which has also been shown to demonstrate some tumor suppression activity. TIG1 is thought to be a transmembrane protein, and its mechanism of tumor suppression is largely unknown.
Leronlimab is a humanized monoclonal antibody targeted against the CCR5 receptor found on T lymphocytes of the human immune system. It is being investigated as a potential therapy in the treatment of COVID-19, triple negative breast cancer, and HIV infection. The United States Food and Drug Administration has designated PRO 140 for fast-track approval. In February 2008, the drug entered Phase 2 clinical trials and a phase 3 trial was begun in 2015. In February 2018, Cytodyn Inc reported that the primary endpoint had been achieved in the PRO 140 pivotal combination therapy trial in HIV infection. In 2020 CytoDyn submitted a fast-track biologics license application for treatment of CCR5-tropic HIV-1 Infection.
Salmon calcitonin (sCT) is the type of calcitonin hormone found in salmon.
Peptide T is an HIV entry inhibitor discovered in 1986 by Candace Pert and Michael Ruff, a US neuroscientist and immunologist. Peptide T, and its modified analog Dala1-peptide T-amide (DAPTA), a drug in clinical trials, is a short peptide derived from the HIV envelope protein gp120 which blocks binding and infection of viral strains which use the CCR5 receptor to infect cells.
CCR5 receptor antagonists are a class of small molecules that antagonize the CCR5 receptor. The C-C motif chemokine receptor CCR5 is involved in the process by which HIV, the virus that causes AIDS, enters cells. Hence antagonists of this receptor are entry inhibitors and have potential therapeutic applications in the treatment of HIV infections.
Many major physiological processes depend on regulation of proteolytic enzyme activity and there can be dramatic consequences when equilibrium between an enzyme and its substrates is disturbed. In this prospective, the discovery of small-molecule ligands, like protease inhibitors, that can modulate catalytic activities has an enormous therapeutic effect. Hence, inhibition of the HIV protease is one of the most important approaches for the therapeutic intervention in HIV infection and their development is regarded as major success of structure-based drug design. They are highly effective against HIV and have, since the 1990s, been a key component of anti-retroviral therapies for HIV/AIDS.
Lixisenatide is a once-daily injectable GLP-1 receptor agonist for the treatment of type 2 diabetes.
VIR-576 is an experimental drug that is under clinical trials for the treatment of HIV-1 infections. VIR-576 is synthetic peptide that binds to HIV-1's hydrophobic fusion peptide gp41, preventing the virus from inserting itself into a host cell's membrane to initiate an infection. This drug is a synthesized variant of a highly specific natural entry inhibitor designated as VIRIP.
Fostemsavir, sold under the brand name Rukobia, is an antiretroviral medication for adults living with HIV/AIDS who have tried multiple HIV medications and whose HIV infection cannot be successfully treated with other therapies because of resistance, intolerance or safety considerations.
Centruroides suffusus suffusus toxin II (CssII) is a scorpion β-toxin from the venom of the scorpion Centruroides suffusus suffusus. CssII primarily affects voltage-gated sodium channels by causing a hyperpolarizing shift of voltage dependence, a reduction in peak transient current, and the occurrence of resurgent currents.
Bulevirtide, sold under the brand name Hepcludex, is an antiviral medication for the treatment of chronic hepatitis D.
DKK-SP1 is one of the many neurotoxins present in the scorpion Mesobuthus martensii. This toxin inhibits the voltage-gated sodium channel Nav1.8.
In the management of HIV/AIDS, HIV capsid inhibitors are antiretroviral medicines that target the capsid shell of the virus. Most current antiretroviral drugs used to treat HIV do not directly target the viral capsid. These have also been termed "Capsid-targeting Antivirals", "Capsid Effectors", and "Capsid Assembly Modulators (CAMs)". Because of this, drugs that specifically inhibit the HIV capsid are being developed in order to reduce the replication of HIV, and treat infections that have become resistant to current antiretroviral therapies.