In silico study of the phytochemical Resveratrol with viral and cellular targets for the treatment of Zika infections

SEPÚLVEDA CS; MÁRQUEZ AB; ALAIMO A*; RUSSO CA; GARCÍA CC*

Virtual - Chile y Argentina

Conferencia; 2nd Women in Bioinformatics & Data Science LA Conference; 2021

UNIVERSIDAD DE TALCA (CHILE), FUNDACIÓN INSTITUTO LELOIR Y UNIVERSIDAD NACIONAL DE QUILMES (ARGENTINA).

Resveratrol (3, 5, 4´-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol mainly found in red wine, skin of red grapes, berries, dark chocolate peanuts, and seeds. Its antiviral effects are associated with inhibitions of viral replication, protein synthesis, gene expression, and nucleic acid synthesis. Resveratrol (RES) has been determined to have an antiviral effect against Zika virus (ZIKV). ZIKV is a member of the Flaviviridae family and is transmitted to humans mainly by Aedes mosquitoes. Symptomatic infection in human beings normally results in a mild and self-limiting febrile disease, although it is possible association with more serious sequelae such as Guillain-Barré syndrome, and microcephaly in newborn infants. Despite its association with these severe outcomes, there is no vaccine or effective antiviral agent for ZIKV. Therapies against viruses can be classified into drugs that target the virus and drugs that act on human cells. To gain some insights on the antiviral mechanism of action of RES, we performed docking studies of potential RES cellular and viral targets. We selected three host cell proteins, aryl hydrocarbon receptor (AHR), dihydroorotate dehydrogenase (DHODH) and guanosine monophosphate reductase 2 (GMRP2) and a viral protein, RNA-dependent RNA polymerase (RdRp). AHR is a transcription factor that regulates gene expression and is a proviral protein for ZIKV replication. Mitochondrial enzymes from the limiting steps of pyrimidine and purine biosynthesis such as DHODH and GMRP2 are essential for RNA virus multiplication. We generated by homology modelling the 3D structure of the ligand binding domain of AHR (PAS-B domain) using SWISS-MODEL server and downloaded the 3D structures of DHODH, GMRP2 and RdRp from RCSB PDB. We used Avogadro and Gaussian09 to drawn and optimized the 3D structure of RES, respectively. Autodock 4.2.6 was utilized to carry out molecular docking. The results showed that RES has a good affinity for DHODH, GMRP2 and RdRp.