Finding Compounds that Inhibit the Dengue DENV-3-NS5 Protein Using Molecular Docking

Advisor(s)

Angela Ahrendt, PhD; Illinois Mathematics and Science Academy

Discipline

Biology

Start Date

21-4-2021 8:50 AM

End Date

21-4-2021 9:05 AM

Abstract

Dengue fever is a disease caused by any of the four related dengue viruses. It is a mosquito-borne disease that mainly occurs in tropical and subtropical regions. As of 2019, approximately 400 million cases of dengue infections occur worldwide while 96 million cases result in dengue fever. Symptoms occur around four to six days after infection and last up to ten days. Furthermore, the dengue virus is classified as a flavivirus. These viruses only encode 10 proteins, one of which is NS5. We are specifically trying to target the NS5 protein in the dengue virus because it is very important to the virus’s life cycle. It is a large protein with two enzyme domains; one which is responsible for avoiding human immune response and the other that is vital for RNA synthesis. In our SIR, we tested a variety of compounds using online resources like PyMol, Chimera, and Swissdock, to see if they bind and inhibit the protein. For example, we used local docking in SwissDock to test the binding of drug-like compounds from the Medicines for Malaria Venture’s boxes to the active sites on the NS5 protein. We compared the different binding poses, Gibbs free energies, and FullFitness values to those of the natural ligands in an effort to prioritize compounds for screening in the lab.

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Apr 21st, 8:50 AM Apr 21st, 9:05 AM

Finding Compounds that Inhibit the Dengue DENV-3-NS5 Protein Using Molecular Docking

Dengue fever is a disease caused by any of the four related dengue viruses. It is a mosquito-borne disease that mainly occurs in tropical and subtropical regions. As of 2019, approximately 400 million cases of dengue infections occur worldwide while 96 million cases result in dengue fever. Symptoms occur around four to six days after infection and last up to ten days. Furthermore, the dengue virus is classified as a flavivirus. These viruses only encode 10 proteins, one of which is NS5. We are specifically trying to target the NS5 protein in the dengue virus because it is very important to the virus’s life cycle. It is a large protein with two enzyme domains; one which is responsible for avoiding human immune response and the other that is vital for RNA synthesis. In our SIR, we tested a variety of compounds using online resources like PyMol, Chimera, and Swissdock, to see if they bind and inhibit the protein. For example, we used local docking in SwissDock to test the binding of drug-like compounds from the Medicines for Malaria Venture’s boxes to the active sites on the NS5 protein. We compared the different binding poses, Gibbs free energies, and FullFitness values to those of the natural ligands in an effort to prioritize compounds for screening in the lab.