"COMPUTATIONAL INSIGHTS INTO ANDROGRAPHIS PANICULATA L. AS AN EBOLA VP35 INHIBITOR"

Background: Ebola virus disease (EVD) is also known as Ebola Hemorrhagic Fever (EHF) is a very dangerous disease and often fatal that is characterized by the Ebola virus that belongs to the family of filoviridae. Among them, the Zaire ebolavirus species – is characterized by the highest lethality which ranges in between 90%. EVD has remained pathogenic to human health since the year 1976 and the largest outbreak which started in the year 2014 continued up to 2016 in West African sub-region with over 28,600 cases and 11,325 deaths. Interestingly, Ebola virus encodes seven proteins, and VP35 is known to be involved in the viral genome replication as well as its ability to evade the host immune response; therefore, it becomes a potential target for antiviral intervention. Objective: This study explores the potential of compounds from Andrographis paniculata L. (Kalmegh) as a suitable inhibitor of the Ebola VP35 protein applying only computational methods. Methods: Eight phytochemicals of Andrographis paniculata L. along with their structure–activity relationship were considered in the virtual screening and molecular docking studies to analyse the interaction of phytochemicals with the VP35 protein. Results: Among all these molecules, Andrographidine A and Andrographidine C were identified as the most potent molecules which displayed over -8 kcal/mol of binding affinities. By employing pkCSM and SwissADME, the pharmacokinetic properties and drug-likeness of these compounds was determined. The calculated findings showed that both Andrographidine A and C have good ADME properties and moderate safety coefficients. Furthermore, these compounds met the requirement of Lipinski’s rule of five that is used to determine the biopharmaceutical variety as well as the ease of having adequate oral bioavailability. Conclusions: Thus, it is expected that Andrographidine A and Andrographidine C can act as a VP35 inhibitor providing a basis for the development of novel antiviral compounds against the Ebola virus. However, more specific in-vitro and in-vivo experiments are required to prove these in-silico findings and thus effectively determine the therapeutic efficacy of these compounds. Hence, this work depicts the potential of natural product sources in antiviral drug development and the usefulness of computational chemistry approaches in the discovery of potential therapeutic entities.