Drug Molecule Design And Synthesis Of Anti-Zika Virus Inhibitors

Zika virus(ZIKV)is an enveloped virus with positive-sense single-stranded and Icosahedral structure RNA genome belonging.Virus particle diameter is 40 nm,the inner layer has a dense core.Zika virus disease is one of a self-limiting mosquito-borne acute infectious disease caused by Zika virus and is named for zika forests found in Uganda.Mosquitoe,named as Aedes aegypti transmit ZIKV to humans;Zika virus,also Dengue,West Nile,Spondweni,Japanese encephalitis virus,all belong to family Flaviviridae.Common clinical symptoms of Zika virus disease are fever,spotted papules,headache,joint pain,myalgia,weakness and non-purulent con-junctivitis.Recent studies have shown that infection with ZIKV may cause adult Guillain-Barre syndrome and infant microcephaly and other neurological deficiencies in the newborn.The neurological complications and the severe repercussions of ZIKV infection on the fetus have led the World Health Organization to declare a global health emergency and compel the scientific community to find solutions to the Zika threat.Unf-ortunately,there is no targeted vaccine and specific antiviral inhibitors.The paper hopes to have a breakthrough in small molecule inhibitors of antiviral.The main contents of this paper are as follows:(1)Based on screening and combined with the reported articles,the potential positive drug was selected;(2)Using 2-Fluoro-4-bromoxynil as the starting material and then processed through N-alkylation,cyclization,deprotection,Ullmann coupling,hydrolysis reaction to synthesize positive drug;(3)Based on the positive drug,try to have a structural transformation to synthesize 22 new structures,and all the target compounds were confirmed by ~1HNMR,MS;(4)The target compounds were subjected to cell activity,enzyme activity and other biological Activity evaluation,moreover,five of these compounds were found to exhibit good virus inhibitory activity.Based on this result,a preliminary structure-activity analysis was performed using PharmaGo software.