The Public Health Emergency of International Concern declared the widespread outbreak of SARS-CoV-2 as a global pandemic emergency, which has resulted in 1,773,086 confirmed cases including 111,652 human deaths, as on 13 April 2020, as reported to World Health Organization. As of now, there are no vaccines or antiviral drugs declared to be officially useful against the infection. Saikosaponin is a group of oleanane derivatives reported in Chinese medicinal plants and are described for their anti-viral, anti-tumor, anti-inflammatory, anticonvulsant, antinephritis and hepatoprotective activities. They have also been known to have anti-coronaviral property by interfering the early stage of viral replication including absorption and penetration of the virus. Thus, the present study was undertaken to screen and evaluate the potency of different Saikosaponins against different sets of SARS-CoV-2 binding protein via computational molecular docking simulations. Docking was carried out on a Glide module of Schrodinger Maestro 2018-1 MM Share Version on NSP15 (PDB ID: 6W01) and Prefusion 2019-nCoV spike glycoprotein (PDB ID: 6VSB) from SARS-CoV-2. From the binding energy and interaction studies, the Saikosaponins U and V showed the best affinity towards both the proteins suggesting them to be future research molecule as they mark the desire interaction with NSP15, which is responsible for replication of RNA and also with 2019-nCoV spike glycoprotein which manage the connection with ACE2.

Aim: In view of the strong immunomodulatory and antiviral activity of andrographolide and its derivative, the present study aimed to investigate the binding a nities of andrographolide and its derivative 14deoxy-11,12-didehydroandrographolide with 3 major targets of COVID-19 i.e. 3CLpro, PLpro and spike protein followed by their gene-set enrichment analysis with special reference to immune modulation. Materials and methods: SMILES of the compounds were retrieved from DigepPred database and the proteins identi ed were queried in STRING to evaluate the protein-protein interaction and modulated pathways were identi ed concerning the KEGG database. Drug-likeness and ADMET pro les were evaluated using MolSoft and admet SAR 2.0, respectively. Molecular docking was carried using autodock 4.0. Results: Andrographolide and 14-Deoxy-11,12-didehydroandrographolide were predicted to have a high binding a nity with papain-like protease i.e.-6.7 kcal/mol and-6.5 kcal/mol, respectively while they interact with equal binding energies with 3clpro (-6.8 kcal/mol) and spike protein (-6.9 kcal/mol). Network pharmacology analysis revealed that both compounds modulated the immune system through the regulation of chemokine signaling pathway, Rap1 signaling pathway, Cytokine-cytokine receptor interaction, MAPK signaling pathway, NF-kappa B signaling pathway, Rassignaling pathway, p53 signaling pathway, HIF-1 signaling pathway, and Natural killer cell-mediated cytotoxicity. Although the 14deoxy-11,12-didehydroandrographolide scored higher drug-likeness character, it showed less potency to interaction with targeted proteins of COVID-19. Conclusion: The study suggests the strong interaction of the andrographolide and its derivative 14-deoxy-11,12-didehydroandrographolide against target proteins associated with COVID-19. Further, network pharmacology analysis elucidated the different pathways of immunomodulation. However, clinical research should be conducted to con rm the current ndings.

COVID-19 has ravaged the world and is the greatest of pandemics in modern human history, in the absence of treatment or vaccine, the mortality and morbidity rates are very high. The present investigation identifies potential leads from the plant Withania somnifera (Indian ginseng), a well-known antiviral, immunomodulatory, anti-inflammatory and a potent antioxidant plant, using molecular docking and dynamics studies. Two different protein targets of SARS-CoV-2 namely NSP15 endoribonuclease and receptor binding domain of prefusion spike protein from SARS-CoV-2 were targeted. Molecular docking studies suggested Withanoside X and Quercetin glucoside from W. somnifera have favorable interactions at the binding site of selected proteins, that is, 6W01 and 6M0J. The top-ranked phytochemicals from docking studies, subjected to 100 ns molecular dynamics (MD) suggested Withanoside X with the highest binding free energy (DG bind ¼ À89.42 kcal/mol) as the most promising inhibitor. During MD studies, the molecule optimizes its conformation for better fitting with the receptor active site justifying the high binding affinity. Based on proven therapeutic, that is, immunomodulatory, antioxidant and anti-inflammatory roles and plausible potential against n-CoV-2 proteins, Indian ginseng could be one of the alternatives as an antiviral agent in the treatment of COVID 19. HIGHLIGHTSWithania somnifera has antiviral potential. Phytochemicals of Ashwagandha showed promising in silico docking and molecular dynamics results.

COVID-19 has ravaged the world and is the greatest of pandemics in human history, in the absence of treatment or vaccine the mortality and morbidity rates are very high. The present investigation was undertaken to screen and identify the potent leads from the Indian Ayurvedic herb, Asparagus racemosus (Willd.) against SARS-CoV-2 using molecular docking and dynamics studies. The docking analysis was performed on the Glide module of Schr€ odinger suite on two different proteins from SARS-CoV-2 viz. NSP15 Endoribonuclease and spike receptor-binding domain. Asparoside-C, Asparoside-D and Asparoside -F were found to be most effective against both the proteins as confirmed through their docking score and affinity. Further, the 100 ns molecular dynamics study also confirmed the potential of these compounds from reasonably lower root mean square deviations and better stabilization of Asparoside-C and Asparoside-F in spike receptor-binding domain and NSP15 Endoribonuclease respectively. MM-GBSA based binding free energy calculations also suggest the most favourable binding affinities of Asparoside-C and Asparoside-F with binding energies of À62.61 and À55.19 Kcal/mol respectively with spike receptor-binding domain and NSP15 Endoribonuclease. HIGHLIGHTSAsparagus racemosus have antiviral potential Phytochemicals of Shatavari showed promising in-silico docking and MD results Asparaoside-C and Asparoside-F has good binding with target proteins Asparagus racemosus holds promise as SARS-COV-2 (S) and (N) proteins inhibitor

These potentially versatile molecular interactions of NTZ within invading pathogen(s) and immunomodulatory efficacy over the hosts, justify the multifunctional chemotherapeutic significance of this chemical agent.