Introduction: Human immunodeficiency virus (HIV) is a retrovirus that belongs to the
Retroviridae family and the Lentivirus genus. Since HIV was discovered, over 64.9 million
people globally were infected with HIV. In 2013, approximately 35 million people were
living with HIV (WHO). The hallmark of HIV infection is the depletion of the CD4+T-cells
in the blood circulation. The infection of HIV begins with the binding between the viral
envelope glycoprotein (Env) gp120 and CD4 receptor and further binding to chemokine coreceptors,
CCR5 or CXCR4. The interactions subsequently trigger viral Env gp41 to mediate
virus-induced membrane fusion, leading to a successful entry event.1, 2 Thus, blocking of the
virus to enter its host cell at the first place has made steps of entry promising drug targets.
Currently, there are only two FDA-approved entry inhibitors: enfuvirtide and maraviroc.
Enfuvirtide (T20) blocks the virus-induced membrane fusion by competitively binding to
gp41 while maraviroc blocks the binding of gp120/CD4 complex to CCR5.3 Recently, HIV-1
that are resistant to the entry inhibitors were reported.4 With the occurrence of antiretroviral
drug resistance viruses as well as the fact that only two entry inhibitors are approved, the
development of novel anti-HIV agents that block at the entry step is needed.
Introduction: Human immunodeficiency virus (HIV) is a retrovirus that belongs to theRetroviridae family and the Lentivirus genus. Since HIV was discovered, over 64.9 millionpeople globally were infected with HIV. In 2013, approximately 35 million people wereliving with HIV (WHO). The hallmark of HIV infection is the depletion of the CD4+T-cellsin the blood circulation. The infection of HIV begins with the binding between the viralenvelope glycoprotein (Env) gp120 and CD4 receptor and further binding to chemokine coreceptors,CCR5 or CXCR4. The interactions subsequently trigger viral Env gp41 to mediatevirus-induced membrane fusion, leading to a successful entry event.1, 2 Thus, blocking of thevirus to enter its host cell at the first place has made steps of entry promising drug targets.Currently, there are only two FDA-approved entry inhibitors: enfuvirtide and maraviroc.Enfuvirtide (T20) blocks the virus-induced membrane fusion by competitively binding togp41 while maraviroc blocks the binding of gp120/CD4 complex to CCR5.3 Recently, HIV-1that are resistant to the entry inhibitors were reported.4 With the occurrence of antiretroviraldrug resistance viruses as well as the fact that only two entry inhibitors are approved, thedevelopment of novel anti-HIV agents that block at the entry step is needed.
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