#199 Structure aided drug development of potential antiviral agents against chikungunya virus

Abstract

The recent upsurge of viral infections due to viruses such as Ebola, Chikungunya, Zika, Nipah, SARS-CoV-2 led to global distress that drove the focal point on the development of promising antiviral molecules. We have centered our research mainly on the development of potential molecules against Chikungunya which outbreaks into a severe epidemic. Although there is no definite treatment, studies have indicated that drugs like Chloroquine, Arbidol, Thiazolidine derivatives inhibit viral cell entry; out of which Nitazoxanide is reported to be efficient against Chikungunya. It consists of a thiazole scaffold common in many experimental and approved drugs. Consequently, the versatile pharmacological nature of the thiazole scaffold led us to choose it for further exploration along with isostere five-membered heterocycles – imidazole and oxazole for screening of activity against entry spike glycoprotein (E2) of Chikungunya virus. In-silico molecular docking was used to focus on binding interactions of the designed thiazole and analogous scaffolds in the glycoprotein complex of the Chikungunya virus. Docking software Glide7.4 with Maestro11.1 and ADME screening using QikProp5.1 (Schrodinger, LLC, New York, NY, 2019) were used for this purpose. The set of drug analogs showing promising interactions was synthesized and characterized using FTIR and NMR. The in-vitro evaluation is ongoing. It was revealed from docking studies that all designed molecules showed potential interactions with the E2 glycoprotein of the Chikungunya virus. Out of these molecules, some which showed stronger interactions were synthesized and subjected to ADME studies, which also displayed optimistic results. The in-silico studies concluded that all three series of thiazole, oxazole, imidazole showed properties likely to that of established drugs. From this, it can be inferred that good antiviral activity against chikungunya might be possessed by furanamido analogs of thiazole, oxazole, imidazole.