**Abstract**

The importance of studying the human papillomavirus (HPV) is because it is a disease that relies on 14 HPV types classified as carcinogenic high risk and that contributes to cervical cancers affecting approximately 527,600 women yearly and causing 265,387 deaths yearly, being the second mortality cause for women globally. In Mexico, 13.9% of demises are due to cervical uterine cancer (CUCA). The challenges for a vaccine that may prevent HPV occurrence are an active field for scientists with significant advances but still undergoing for a full cure to this disease. In this work, latest research trends to treat HPV are analyzed, and by means of molecular coupling analysis, a modeling and simulation process to predict interactions of leader molecules with the target for synthetic elaboration of a possible therapeutic treatment is developed. One of the main topics discussed in this chapter relates to new drug design for HPV treatment, which is related to the inhibitors of protein-protein interactions and in the protein drugs. Regarding HPV therapy development, a group of small molecules has been identified using high-performance sieving capable of interrupting HPV16 E1-E2 interaction, which helps avoid viral replication. Some of these compounds displayed nanomolar affinities and high specificity.

**Keywords:** viral proteins, human papillomavirus, HPV, E1-E2 proteins, TDDFT
