This article needs to be updated. Please help update this to reflect recent events or newly available information.(May 2020)
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.
The penetration of the
cell membrane by gp41, which approximates the membrane of HIV and the
T cell and promotes their fusion
The entry of the viral core into the cell
Entry inhibitors work by interfering with one aspect of this process.
Approved agents
Maraviroc binds to
CCR5, preventing an interaction with
gp120. It is also referred to as a "chemokine receptor antagonist" or a "CCR5 inhibitor."[4]
Enfuvirtide binds to gp41 and interferes with its ability to approximate the two membranes. It is also referred to as a "fusion inhibitor."
Ibalizumab, a
monoclonal antibody that binds to domain 2 of CD4 and interferes with post-attachment steps required for the entry of HIV-1 virus particles into host cells and prevents the viral transmission that occurs via cell-cell fusion.
Fostemsavir, an attachment inhibitor that interferes with the interaction of CD4 and
gp120 by binding with
gp120.
Investigational agents
Other agents are under investigation for their ability to interact with the proteins involved in HIV entry and the possibility that they may serve as entry inhibitors.[5]
Vicriviroc, similar to maraviroc, is currently undergoing clinical trials for FDA approval.
Aplaviroc, an agent similar to maraviroc and vicriroc. Clinical trials were halted in 2005 over concerns about the drug's safety.
b12 is an
antibody against HIV found in some
long-term nonprogressors. It has been found to bind to
gp120 at the exact region, or
epitope, where
gp120 binds to CD4. b12 seems to serve as a natural entry inhibitor in some individuals. It is hoped that further study of b12 may lead to an effective HIV vaccine.
Griffithsin, a substance derived from algae, appears to have entry inhibitor properties.[7]
DCM205, is a small molecule based on L-
chicoric acid, an integrase inhibitor. DCM205 has been reported to inactivate HIV-1 particles directly in vitro and is thought to act primarily as an entry inhibitor.[8]
CD4 specific Designed
Ankyrin Repeat Proteins (
DARPins) potently block viral entry of diverse strains and are being developed and studied as potential microbicide candidates [9]
A polyclonal
caprine antibody is in phase II human
clinical trials that targets, among others sites, the GP41 transmembrane glycoprotein. The trials are being conducted by Virionyx, a New Zealand Company.[10]
VIR-576 is a synthesized peptide which binds to gp41, preventing fusion of the virus with a cell membrane.
^Biswas P, Tambussi G, Lazzarin A (May 2007). "Access denied? The status of co-receptor inhibition to counter HIV entry". Expert Opinion on Pharmacotherapy. 8 (7): 923–33.
doi:
10.1517/14656566.8.7.923.
PMID17472538.
S2CID32675897.
This article needs to be updated. Please help update this to reflect recent events or newly available information.(May 2020)
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.
The penetration of the
cell membrane by gp41, which approximates the membrane of HIV and the
T cell and promotes their fusion
The entry of the viral core into the cell
Entry inhibitors work by interfering with one aspect of this process.
Approved agents
Maraviroc binds to
CCR5, preventing an interaction with
gp120. It is also referred to as a "chemokine receptor antagonist" or a "CCR5 inhibitor."[4]
Enfuvirtide binds to gp41 and interferes with its ability to approximate the two membranes. It is also referred to as a "fusion inhibitor."
Ibalizumab, a
monoclonal antibody that binds to domain 2 of CD4 and interferes with post-attachment steps required for the entry of HIV-1 virus particles into host cells and prevents the viral transmission that occurs via cell-cell fusion.
Fostemsavir, an attachment inhibitor that interferes with the interaction of CD4 and
gp120 by binding with
gp120.
Investigational agents
Other agents are under investigation for their ability to interact with the proteins involved in HIV entry and the possibility that they may serve as entry inhibitors.[5]
Vicriviroc, similar to maraviroc, is currently undergoing clinical trials for FDA approval.
Aplaviroc, an agent similar to maraviroc and vicriroc. Clinical trials were halted in 2005 over concerns about the drug's safety.
b12 is an
antibody against HIV found in some
long-term nonprogressors. It has been found to bind to
gp120 at the exact region, or
epitope, where
gp120 binds to CD4. b12 seems to serve as a natural entry inhibitor in some individuals. It is hoped that further study of b12 may lead to an effective HIV vaccine.
Griffithsin, a substance derived from algae, appears to have entry inhibitor properties.[7]
DCM205, is a small molecule based on L-
chicoric acid, an integrase inhibitor. DCM205 has been reported to inactivate HIV-1 particles directly in vitro and is thought to act primarily as an entry inhibitor.[8]
CD4 specific Designed
Ankyrin Repeat Proteins (
DARPins) potently block viral entry of diverse strains and are being developed and studied as potential microbicide candidates [9]
A polyclonal
caprine antibody is in phase II human
clinical trials that targets, among others sites, the GP41 transmembrane glycoprotein. The trials are being conducted by Virionyx, a New Zealand Company.[10]
VIR-576 is a synthesized peptide which binds to gp41, preventing fusion of the virus with a cell membrane.
^Biswas P, Tambussi G, Lazzarin A (May 2007). "Access denied? The status of co-receptor inhibition to counter HIV entry". Expert Opinion on Pharmacotherapy. 8 (7): 923–33.
doi:
10.1517/14656566.8.7.923.
PMID17472538.
S2CID32675897.