Research Projects

HIV-HCV coinfection is a significant issue, with 90% of intravenous drug users experiencing it. Currently, only two anti-retroviral drugs, rilpivirine and carbotegravir, have limitations in their biodistribution and pharmacokinetic profile. To improve patient adherence, decrease drug toxicity, and suppress the virus for longer, a new extended-release anti-retroviral formulation is needed. Emtricitabine with Tenofovir disoproxil fumarate has been used against HIV/HCV coinfection in adults infected with both HCV and HIV. However, the polar nature of Emtricitabine limits its efficient cellular uptake. To address this, a new long-acting, stable, and potent prodrug Emtricitabine (FTC) conjugates with longer half-life and broad-spectrum activity against drug-resistant HIV is proposed. Log chain fatty acids, which are lipophilic in nature, can be conjugated with hydrophilic drugs like Emtricitabine to create lipophilic conjugates. This research project proposes the modification of Emtricitabine (FTC) with long-chain fatty acids analog and its extended release nano-formulation with biodegradable natural surfactants to improve its lipophilicity, enhanced cellular uptake, reduced toxicity, long-acting effect, and higher stability. Fatty acids also have modest anti-HCV activity, and the conjugation of these analogs may be beneficial for synergistic anti-HIV and anti-HCV activity. Designing different fatty acid conjugates of Emtricitabine with Molinspiration toolkit and docking analysis using the CDOCKER protocol for Discovery studio 2.5 will be done. The synthesized compounds will be purified by column chromatography and HPLC, and in-vitro anti-HIV and anti-HCV screening will be conducted using different cell lines. The most active conjugate against both HIV and HCV will be selected for nanoformulation development using natural surfactants.