**4.7. Natural derivatives with anti-retroviral property**

**Phase of HIV replication**

Cytoplasmic export of

Maturation of progeny

Enhancing the anti-viral restriction factors of the

Direct destruction of free

Selective cytolysis of HIV

HIV virions

infected cells

after release

host cell

**Novel mechanism of action Compound Reference**

PKF050-638 [58]

BIT225 [62]

Bevirimat [63]

Chicoric acid derivatives [64]

SN-2 [68]

Acylhydrazone derivatives [70]

Ceragenins (CSA-54) [71]

Ciclopirox and deferiprone [72]

Aminoglcosides (Neomycin,

RN-18 [65, 66] VEC-5 [67]

2-(quinolin-3-yl) acetic acid

derivatives

netilmicin)

[59, 60]

[61]

[21]

[47]

Rhodanine and triazine

benzodiazepines and benzimidazoles

compounds

Inhibition of host proteins involved in nuclear export of HIV mRNA

Blocking the ion channel function of the

Preventing the release of capsid protein from its precursor protein in the progeny virions and thereby rendering

growth factor protein p75 (LEDGF/p75) which helps in viral DNA integration

Inhibition of HIV virion infectivity factor (vif) to indirectly improve the viral restriction by APOBEC proteins

Multiple steps Inhibition of uncoating and assembly Thiourea compounds [69]

Although most of these compounds have shown potent *in vitro* anti-retroviral activity, their *in vivo* efficacy needs to be evaluated. A few of the listed drug candidates are undergoing clinical trials and are expected to be available for use in the near future. The concept of using antiviral compounds for treatment of HIV poses a significant drawback. Unlike other viruses,

Direct enhancement of APOBEC

Inhibition of viral entry and

**Table 3.** Novel synthetic anti-retroviral compounds and their mechanism of action

Cation mediated destruction of HIV

Inhibition of acute viral infection and activation of apoptotic pathways specifically in cells infected with HIV

in the initiation of HIV mRNA

218 Trends in Basic and Therapeutic Options in HIV Infection - Towards a Functional Cure

Translation Inhibition of cellular ATPases involved

translation

Assembly and release Binding to capsid protein and Inhibition of assembly

HIV protein vpu

them non-infectious

Viral DNA integration Inhibition of lens epithelium derived

proteins

transcription

envelope

**inhibited**

HIV mRNA

Apart from the multitude of synthetic anti-retroviral compounds that are being generated every day, many naturally occurring compounds have also been identified to inhibit HIV [74, 75]. Plants, marine organisms, arthropod venoms and bacteria form the principal sources of these compounds. Extracts from natural sources are tested *in vitro* for anti-retroviral activity and the most active component identified, purified and studied for possible mechanism of action. Interestingly, some of the natural compounds have been found to perform better than their synthetic counterparts [73]. Recently, virtual methods are being developed for screening natural compounds for their anti-retroviral property [76]. If the *in vitro* effects could be effectively achieved *in vivo*, it would not be surprising when some of these compounds soon make their way across clinical trials and be available for use in the near future. Table-4 summarizes some recent compounds of renewed interest among various naturally occurring anti-retroviral compounds already identified.



**Table 4.** Anti-retroviral compounds isolated from natural sources
