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Elucidating Molecular Interactions of Ten Natural Compounds Targeting E6 HPV High Risk Oncoproteins Using Microsecond Molecular Dynamics Simulations


Thuluz Meza-Menchaca, Marcela Lizano-Soberón, Angel Trigos, Rossana C. Zepeda, Manuel E. Medina and Rodrigo Galindo-Murillo*   Pages 1 - 14 ( 14 )


Background: Cervical cancer is a major public health issue worldwide, occurring in the vast majority of cases (85%) in low-income countries. Human papillomavirus (HPV) mainly infects the mucosal epithelium, and a small portion causes over 600,000 cases every year worldwide at various anatomical spots, mainly leading to anogenital and head and neck.

Introduction: The E6 oncoprotein encoded by cancer-associated alpha HPV can transform epithelial cells into tumorigenic tissue. Therapy for this infection and blocking of the HPV E6 oncoprotein could be provided with cost-effective and abundant natural products which are an exponentially growing topic in the literature. Finding an active natural compound that readily blocks HPV E6 oncoprotein which could be available for developing countries without expensive extraction processes or costly synthetic pathways is of major interest.

Method: Molecular dynamics simulations was performed using the most up-to-date AMBER protein force field ff14SB and a GPU enabled high performance computing cluster.

Results: In this research we present a study of the binding properties between 10 selected natural compounds that are readily available with two variants of the E6 oncoprotein types (HPV-16 and HPV-18) using 10+ microsecond molecular dynamics simulations.

Conclusions: Our results suggest that crocetin, ergosterol peroxide and κ-carrageenan natural products binds strongly to both HPV-16 and HPV-18 and could potentially serve as a scaffolding for further drug development.


HPV, E6, AMBER, Cervical cancer, Natural compounds


Facultad de Medicina. Laboratorio de Genómica Humana. Universidad Veracruzana. Médicos y Odontólogos, Col. Unidad del Bosque, 91010, Xalapa, Veracruz, Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 14080, Ciudad de México, Centro de Investigación en Micología Aplicada. Universidad Veracruzana. Xalapa, Veracruz, Centro de Investigaciones Biomédicas, Universidad Veracruzana, Av. Luis Castelazo Ayala. Xalapa-Enríquez, Veracruz 91190, Centro de Investigaciones Biomédicas, Universidad Veracruzana, Av. Luis Castelazo Ayala. Xalapa-Enríquez, Veracruz 91190, Department of Medicinal Chemistry, L.S. Skaggs Pharmacy Institute, University of Utah, Salt Lake City, Utah 84112

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