**Acknowledgements**

*Viruses and Viral Infections in Developing Countries*

Ser574, Asp573 of HPV16 E1, respectively.

used for suppression of HPV replication [55].

are capable of preventing HPV replication.

of small molecular inhibitors for E1-E2 interaction [53].

assays of approximately 1 mM, make this series a promising route for development

Capabilities of indandione compounds to inhibit HPV genome in vivo replication, especially low-risk HPV types, demonstrate for the first time the therapeutic potential of protein E2 as target for the development of small molecule inhibitors at HPV protein interaction, particularly in the case for treatment of anogenital warts caused by HPV6 and HPV11. Furthermore, location and characterization of the union bag for E2 TAD inhibitors provide a new potential therapeutic option for treatment of HPV infections. These studies have set the basis for the use of approaches based in structures for rational design or for virtual selection of inhibitor compounds capable of joining to all or part of the identified inhibitor union bag. Kantang and coworker worked in the prediction of the interactions of the helicase domain of the E1 protein of HPV16 and the TAD domain of HPV16; for this purpose, E1 protein domain was modeled (residue 421–622) from HPV16 with I-TASSER server. The model with the best C-score was selected to coupling to structure E2 from HPV16 and HPV18 using ClusPro. Superposition of E1 HPV16 and the crystalline structure of E1 HPV18 showed an RMSD of 1.39 Å, indicating structural similitude. A complex structure for HPV16 E1-E2 is also predicted as similar to crystalline structure of HPV18 E1-E2, with an RMSD value of 1.11 Å. An analysis of HPV16 E1-E2 interactions revealed there are three sites for interaction of complex HPV16 E1 and E2. The residues Glu118, and Tyr178 at the structural domain of folded β-sheet for HPV16 E2 form hydrogen bonds with Tyr578, Arg575,

HPV16 E2 helicoidal N-terminal domain is the main union site for HPV16 E1 protein where Asp13, Thr17, Tyr19, Asp22, Tyr32, Glu39, and Val58 from HPV16 E2 interact with Arg615 (for Asp13 and Thr17 E2), Arg447, Arg619, Glu452, Arg447, and Tyr602 from HPV16 E1, respectively. Shows Gln95 and Glu100; at the linking segment between N-terminal and C-terminal HPV16 E2, there are interactions with Arg462 and Ser455 from HPV16 E1, respectively. Besides, structures of nine peptides reported [54] were built by I-TASSER server. Using ClusPro web server, it was able to predict binding, conformations, and interactions of peptides with HPV16 E2 protein; bind conformations and interactions between small peptides and HPV16 E2 protein were predicted and analyzed. These results were used ahead for the design of more powerful peptides that may potentially inhibit E1-E2 complex formation. Binding affinities obtained for designed peptides and protein E2 of HPV16 recombinant were in good agreement with experimental results. Four peptides were the more efficient inhibitors of E1-E2 complex, and they could be

Currently a cure or treatment for HPV is unavailable. In many men and women, HPV disappears by itself without causing further problems. There are treatments for affections caused by the virus. Among these affections are genital warts, pre-

Even though there are vaccines against the main HPV types, there are therapeutic treatments needed for those that have been already exposed to the virus which represent most of the population affected by this disease. In this regard, a diversity of research work related to antiviral design exists, including those work using computational methods. These studies have laid the foundation for the use of structurebased approaches to rationally design or virtually screen inhibitory compounds that

**28**

**4. Conclusions**

carcinogenic cells, and cancer.

We thank the Scientific Computational Laboratory at FCQ-UJED for the computational resources and also MBA Fátima Berenice Corrales Saucedo for her contribution with graphic design.
