HIV Related Peptides

• HIV-1 gag Protein Fragments
• HIV Protease Substrates and inhibitors
• CONSENSUS B Tat Fragments
• GP120-W61D Fragments
• HIV-1 CONSENSUS B VIF Fragments
• HIV-1 MN ENV Fragments
• HIV-1 MN gp160 Fragment
• HXB2 gag NO Fragments
• SIVmac239 Fragments
• HIV-1 rev and tat fragments
• HIV-1 MN NO Fragment
• Other Fragments

Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS). This gradual collapse of the cellular immune response exacerbates normally harmless infections and cancers. They are caused by pathogens such as Candida, Mycobacterium tuberculosis or latent herpesvirus (such as EBV, HCMV). In infected persons, HIV exists in the form of free particles and exists in infected immune cells (especially CD4+ cells). The entry of HIV into cells requires the interaction of viral envelope protein gp120 with CD4 glycoprotein and chemokine receptors on the surface of host cells. At the end of 2007, nearly 30 years after the discovery of HIV-1/AIDS, an estimated 33 million people were infected with the virus and 25 million died from the disease. In designing a new strategy for the treatment of HIV-1 infection, one epicenter is the synergistic effect of peptide chemistry and structural biology. A milestone in AIDS treatment is the approval of the first peptide fusion inhibitor.

Mode of Action

HIV-1 infection begins with the binding of viral glycoprotein gp120 to CD4 receptors on T lymphocytes. In this process, co-receptors also play a vital role. According to the type of co-receptor involved, HIV-1 isolates can be divided into three types: X4, R5 and combined X4R5. The X4 virus used the CXCR4 co-receptor, while the R5 strain used the CCR5 co-receptor. Individuals with a 32- base deletions in the CCR5 coding sequence are resistant to HIV-1 infection, which highlights the important role of this common receptor in viral infection. For the early transmission of the founding virus, R5 strain infected CD4+ lymphocytes, but not macrophages. After fusion, HIV-1 releases its RNA into CD4 cells and hijacks these cells to produce more viruses. Under the catalysis of reverse transcriptase, viral RNA must be transcribed into complementary DNA (CDNA). Then, with the help of viral integrase, DNA was integrated into the host genome and reverse transcribed into mRNA for protein expression. After translation, protease treatment and assembly, new viral particles are released from host cells and can infect other cells. Understanding the life cycle of HIV-1 is important for the development of anti-HIV-1 drugs.

Application of peptides in HIV

Therapeutic peptides and proteins as HIV-1 inhibitors have many advantages, such as high specificity and affinity to their molecular targets, and HIV-1 mutants are difficult to avoid these molecules, and are gradually becoming an alternative strategy for HIV-1 therapy. The concept of targeting peptides to membranes to increase receptor interactions has been long known to peptide chemists. These peptides seem to work through different mechanisms and can prevent viruses from entering in a variety of ways. As an additional advantage, such anti-HIV peptides may have other desired functions, such as antibacterial, anti-parasite, spermicidal, and anticancer activities. With the continuous optimization of peptide stability, production, preparation and release methods, some of these compounds are expected to eventually become new anti-HIV drugs.

Conclusion

At present, more and more attention has been paid to the development of peptide therapy. The main advantages of peptides are small size, easy optimization, and special interaction. Compared with small molecules that can’t inhibit protein interaction, the specificity of peptides is one of its important advantages. The disadvantages of peptide therapy are possible toxicity, protease degradation and production costs. However, this will change with the development of high-throughput screening and peptide production methods that can evaluate more natural peptides collected from APD or artificial combinatorial libraries. Future assessments should also take into account the impact of cells and HIV types on the anti-HIV activity of new compounds.

References

1. Lopes, R. S., Queiroz, M. A. F., Gomes, S. T. M., Vallinoto, A. C. R., Goulart, L. R., & Ishak, R. (2018). Phage display: an important tool in the discovery of peptides with anti-HIV activity. Biotechnology advances.
2. Cole, A., & Cole, A. (2017). HIV-enhancing and HIV-inhibiting properties of cationic peptides and proteins. Viruses, 9(5), 108.