Introduction HIV/AIDS pandemic is one of the leading cause of death worldwide and a matter of serious concern to the scientific world. Most of new HIV infections spread through heterosexual mode and leads to HIV-1 induced immune system activation. This renders infected individuals more susceptible to HIV-1 pathogenesis and opportunistic infections. Hence, preventing HIV infections at early stages and neutralising its effect on host cells is essential in combating AIDS epidemic.
Methods Human haemoglobin derived peptide, named HbAHP-25, was designed in silico against CD4 binding domain of gp120 by molecular docking methods. HbAHP-25 was characterised for its inhibitory activity on various strains of HIV-1 in PBMCs in the presence and absence of seminal plasma and vaginal fluid. Specificity of action of HbAHP-25 was determined by HIV-1 pseudotyped assays. Immunofluorescence, Multiplex Cytokine assay and Dual Chamber assays were performed to evaluate safety of HbAHP-25 and its role in modulating immune response to HIV.
Results HbAHP-25 has significant anti-HIV activity against various strains of HIV-1 in a dose dependent fashion. HbAHP-25 binds to a site proximal to CD4 binding site on gp120, has partial epitope similarity with VRC01 on gp120 and inhibits gp120-CD4 interaction. Flow cytometery analysis showed that HbAHP-25 specifically binds to gp120 expressing HL2/3 cells. HbAHP-25 inhibits HIV-1 and doesn’t inhibit HIV-1 pseudotyped virus from entering cells. Further, HbAHP-25 didn’t affect cell viability even at higher concentrations; nor did it have any effect on epithelial monolayer integrity. HbAHP-25 doesn’t elicit any pro-inflammatory response and protects cells from HIV induced inflammation. Results indicate that HbAHP-25 prevents HIV-1 from activating NF-kB pathway, thus limiting its ability to induce cytokines.
Conclusion HbAHP-25 protects cells from HIV-1 entry and HIV-1 induced inflammation by binding proximal to CD4 binding site of gp120. HbAHP-25 maintained good safety profile and can be a potential molecule for pre-clinical development of prophylactic/anti-HIV drug.
Disclosure of interest statement Nothing to declare.
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