Abstract
Infections caused by human immunodeficiency virus (HIV) are considered one of the main public health problems worldwide. Antiretroviral therapy (ART) is the current modality of treatment for HIV-1 infection. It comprises the combined use of several drugs and can decrease the viral load and increase the CD4+ T cell count in patients with HIV-1 infection, thereby proving to be an effective modality. This therapy significantly decreases the rate of morbidity and mortality owing to acquired immunodeficiency syndrome (AIDS) and prolongs and improves the quality of life of infected patients. However, nonadherence to ART may increase viral resistance to antiretroviral drugs and transmission of drug-resistant strains of HIV. Therefore, it is necessary to continue research for compounds with anti-HIV-1 activity, exhibiting a potential for the development of an alternative or complementary therapy to ART with low cost and fewer side effects. Natural products and their derivatives represent an excellent option owing to their therapeutic potential against HIV. Currently, the derivatives of natural products available as anti-HIV-1 agents include zidovudine, an arabinonucleoside derivative of the Caribbean marine sponge (Tectitethya crypta), which inhibits the reverse transcriptase of the virus. This was the first antiviral agent approved for treatment of HIV infection. Additionally, bevirimat (isolated from Syzygium claviflorum) and calanolide A (isolated from Calophyllum sp.) are inhibitors of viral maturation and reverse transcription process, respectively. In the present review, we aimed to describe the wide repertoire of natural compounds exhibiting anti-HIV-1 activity that can be considered for designing new therapeutic strategies to curb the HIV pandemic.
Highlights
Since the emergence of the human immunodeficiency virus (HIV) and with time, the pandemic caused by this virus has been established as one of the main public health problems worldwide, generating new challenges in terms of its prevention and control [1]
Specific issues are associated with the use of antiretroviral therapy (ART), including limited access to medications and various side effects associated with their use, such as lipodystrophy and metabolic disturbances associated with protease inhibitors (PIs), hypersensitivity and hepatotoxicity due to nucleoside reverse transcriptase inhibitors (NRTIs), and mitochondrial toxicity related to non-nucleoside reverse transcriptase inhibitors (NNRTIs) [10, 11], which decrease treatment adherence, favoring the emergence of some viral strains resistant to therapy [12,13,14,15]
To determine the viral cycle step affecting bevirimat, they performed syncytium formation inhibition assays with Molt-4 cells, infectious virus release by multinuclear activation of galactosidase indicator (MAGI) assay with MAGI-CCR5 cells, electron microscopic observation, and the time-ofaddition assay [30]. e compound did not inhibit the formation of syncytia but inhibited the release of virus from infected cells; likewise, p24 antigen expression was different when it was associated to the cell where a variation of the enzyme concentration was observed according to the time of compound addition, while low levels were observed in the supernatant of treated cells. erefore, these findings suggest that bevirimat interferes with HIV-1 assembly or exit [30]
Summary
Since the emergence of the human immunodeficiency virus (HIV) and with time, the pandemic caused by this virus has been established as one of the main public health problems worldwide, generating new challenges in terms of its prevention and control [1]. Is is currently considered the standard treatment for HIV infection [6] and has radically changed the prognosis of HIV infection because ART can reduce the viral load, increases the CD4+ T cells count, and reduces the probability of new opportunistic infections, thereby significantly lowering the morbidity and mortality of AIDS and extending the life of infected individuals [7,8,9]. Erefore, it is important to know the wide repertoire of natural compounds exhibiting anti-HIV activity, considering that their identification is essential for designing new therapeutic strategies to counteract the morbidity and mortality associated with the HIV-1 pandemic. Considering that there is a wide range of natural compounds with potential anti-HIV activity, we mainly focused on terpenes, coumarins, flavonoids, laccases, lectins, ribosome-inactivating proteins (RIPs), and bromotyrosines (Figure 1)
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