Venomous snakebite is a global serious health issue and in India high rate of mortality is caused by Naja naja (Indian cobra). To evaluate anti-cobra venom activity and identify lead molecules in Aegle marmelos, in vitro and in silico screening was carried out. Leaves, stem and root bark of A. marmelos were extracted in ethanol, methanol and hexane and maximum yield was obtained in methanol. All extracts were used for testing in vitro anti-haemolytic, inhibition of antiacetylcholinesterase and anti-proteolytic activities. The results revealed that ethanol extract of root bark has high anti-haemolytic activity, methanol extracts of leaves have the highest inhibitory effect on venom induced anti-acetylcholinesterase activity and ethanol extracts of leaves have maximum anti-proteolytic activity. Docking between 81 phytochemicals from A. marmelos and each of the 14 cobra venom toxic proteins revealed that the plant contains potential molecules for detoxification of all the cobra venom proteins.

Lekshmi et al.: Potential Lead against HCV from Acacia nilotica (L.) Delile Hepatitis C virus infection is the leading cause of chronic liver disease and hepatocellular carcinoma. There is no effective vaccine for hepatitis C virus prevention despite the fact that several vaccines are under development. Currently, the Unites States Food and drug administration approved combination drugs for all genotypes that would help to cure the infection more quickly and efficiently than ever before. However, the high costs, development of various side effects and emergence of drug resistant strains demand the need for new anti-viral to treat different stages of the hepatitis C virus life cycle. Focussing drug candidate from herbal ingredients is the novel approach of pharmaceutical science over the past few decades. In this perspective, the present study aimed to investigate the phytochemicals present in Acacia nilotica (L.) Delile against hepatitis C virus non-structural protein3-4A serine protease. The N-terminal Protease domain of non-structural protein3 along with non-structural protein4A protein is responsible for the cleavage of four polypeptide junctions' viz., non-structural protein3-4A, non-structural protein4A-non-structural protein4B, non-structural protein4B-non-structural protein5A and non-structural protein5A-5B that are essential for viral genome replication. Hence targeting non-structural protein3-4A blocks the replication process. Here, in silico molecular docking study was executed to estimate the efficacy of phytochemicals along with the two Food and drug administration approved hepatitis C virus non-structural protein3-4A inhibitors-Grazoprevir and simeprevir as reference compounds against the selected target. Docking results revealed that about six phytochemicals (+)-Catechin 5-Gallate, Acacetin, (+)-Mollisacacidin, Catechin, Acalinol A and Chlorogenic acid are better than the reference compounds and hence selected as hits. Further, the hit molecules were filtered through analysing druglikeness properties, pharmacokinetics, medicinal chemistry friendliness including pan assay interference compounds and Brenk structural alerts, leadlikeness and finally prediction of potential toxicity and toxic substructure to ascertain a lead molecule. The results obtained in the current study propose Acacetin as the lead molecule for further in vitro and in vivo study.

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Dengue fever is a severe mosquito-borne global health concern caused by the Dengue virus. There are no effective vaccines or anti-virals against dengue, even though several medications are under developmental stages. As we all know, the traditional medicine system mainly depends on plants to treat various types of diseases caused by bacteria, viruses, and other micro-organisms. In this scenario, the present study focussed on identifying the inhibitory potential of phytoconstituents from a well-known antipyretic medicinal herb Andrographis paniculata (Burm.f.) Nees against MTase domain of NS5 protein from the virus and IMPDH2 from the host through Molecular docking to identify the hit compounds and further druglikeness, pharmacokinetics, and toxicity studies were carried out to ascertain a lead candidate. Through molecular interaction results, it was identified that in the case of NS5, about 28 compounds showed the least binding energy than native ligand SAH and were recommended as hits, out of which 12 compounds interact specifically with the active site residues and were selected as top hits. In the case of IMPDH2, 13 compounds were identified as hits since they showed less binding energy than native ligand RVP, and among that, nine compounds were selected as top hits based on their interaction with the active site residues. Furthermore, the selected hit molecules were subjected to drug-likeness, pharmacokinetics, and toxicity prediction and identified Oleanolic acid as the best lead candidate against both the targets NS5 and IMPDH-II. The study further emphasizes Oleanolic acid as the best lead candidate because naturally, triterpenoid compounds possess anti-viral activity but further in vitro and in vivo studies are essential to propose Oleanolic acid as an anti-dengue compound.