Journal of the Serbian Chemical Society 2022 Volume 87, Issue 6, Pages: 693-706
https://doi.org/10.2298/JSC210929011D
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In silico identification of novel allosteric inhibitors of Dengue virus NS2B/NS3 serine protease
da Costa Renato A. 
(Federal Institute of Education, Science and Technology of Pará - Campus Castanhal, Castanhal, Brazil)
da Rocha João A.P. (Federal Institute of Education, Science and Technology of Pará - Campus Bragança, Bragança, Brazil)
Pinheiro Alan S. (Graduate Program in Chemistry, Institute of Exact and Natural Sciences, Federal University of Pará (UFPA), Belém, Brazil)
da Costa Andréia S.S. (Graduate Program in Science and Environment, Institute of Exact and Natural Sciences, Federal University of Pará (UFPA), Belém, Brazil)
da Rocha Elaine C.M. (Federal Rural University of the Amazon Campus Capanema (UFRA), Capanema, Brazil)
Josino Luiz P.C. (Graduate Program in Chemistry, Institute of Exact and Natural Sciences, Federal University of Pará (UFPA), Belém, Brazil)
da Gonçalves Arlan Silva (Federal Institute of Education, Science and Technology Technology of Espírito Santo Campus Vila Velha, Vila Velha, Brazil)
Lima Anderson H.L. (Graduate Program in Chemistry, Institute of Exact and Natural Sciences, Federal University of Pará (UFPA), Belém, Brazil)
Brasil Davi S.B. (Graduate Program in Science and Environment, Institute of Exact and Natural Sciences, Federal University of Pará (UFPA), Belém, Brazil)
Although dengue is a disease that affects more than 100 countries and puts almost 400 million lives at risk each year, there is no approved antiviral in the treatment of this pathology. In this context, proteases are potential biological targets since they are essential in the replication process of this virus. In this study, a library of more than 3,000 structures was used to explore the allosteric inhibition of the NS2B/NS3 protease complex using consensual docking techniques. The results show four best ranked structures that were selected for molecular dynamics and free energy simulations. The present analysis corroborates with other studies (experimental and theoretical) presented in the literature. Thus, the computational approach used here proved to be useful for planning new inhibitors in the combat against Dengue disease.
Keywords: NS2B/NS3pro, consensual docking, molecular dynamics, binding free energy calculations
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