In-silico investigation of phytochemicals from Asparagus racemosus as plausible antiviral agent in COVID-19.

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 Schrödinger 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 -62.61 and -55.19 Kcal/mol respectively with spike receptor-binding domain and NSP15 Endoribonuclease. HighlightsAsparagus racemosus have antiviral potentialPhytochemicals of Shatavari showed promising in-silico docking and MD resultsAsparaoside-C and Asparoside-F has good binding with target proteinsAsparagus racemosus holds promise as SARS-COV-2 (S) and (N) proteins inhibitor Communicated by Ramaswamy H. Sarma.

Sars-cov-2 host entry and replication inhibitors from Indian ginseng: an in-silico approach.

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 (ΔGbind = -89.42 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. Communicated by Ramaswamy H. Sarma.

Computational and network pharmacology studies of Phyllanthus emblica to tackle SARS-CoV-2.

Background: Since December 2019, SARS-CoV-2 had been a significant threat globally, which has accounted for about two million deaths. Several types of research are undergoing and have reported the significant role of repurposing existing drugs and natural lead in the treatment of COVID-19. The plant Phyllanthus emblica (Synonym-Emblica officinalis) (Euphorbiaceae) is a rich source of vitamin C, and its use as an antiviral agent has been well established. Purpose: The present study was undertaken to investigate the potency of the several components of Phyllanthus emblica against three protein targets of 2019-nCoV viz. NSP15 endoribonuclease, main protease, and receptor binding domain of prefusion spike protein using molecular docking and dynamics studies. Methods: The docking simulation studies were carried out using Schrödinger maestro 2018-1 MM share version, while dynamics studies were conducted to understand the binding mechanism and the complexes' stability studies. Results: Out of sixty-six tested compounds, Chlorogenic acid, Quercitrin, and Myricetin were most effective in showing the highest binding energy against selected protein targets of SARS-CoV-2. The network pharmacology analysis study confirmed these compounds' role in modulating the immune response, inflammatory cascade, and cytokine storm through different signaling pathways. Conclusion: Current pharmacoinformatic approach shows possible role of Phyllanthus emblica in the treatment and management of COVID-19.

Pharmacoinformatics-based identification of transmembrane protease serine-2 inhibitors from Morus Alba as SARS-CoV-2 cell entry inhibitors.

Transmembrane protease serine-2 (TMPRSS2) is a cell-surface protein expressed by epithelial cells of specific tissues including those in the aerodigestive tract. It helps the entry of novel coronavirus (n-CoV) or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the host cell. Successful inhibition of the TMPRSS2 can be one of the crucial strategies to stop the SARS-CoV-2 infection. In the present study, a set of bioactive molecules from Morus alba Linn. were screened against the TMPRSS2 through two widely used molecular docking engines such as Autodock vina and Glide. Molecules having a higher binding affinity toward the TMPRSS2 compared to Camostat and Ambroxol were considered for in-silico pharmacokinetic analyses. Based on acceptable pharmacokinetic parameters and drug-likeness, finally, five molecules were found to be important for the TMPRSS2 inhibition. A number of bonding interactions in terms of hydrogen bond and hydrophobic interactions were observed between the proposed molecules and ligand-interacting amino acids of the TMPRSS2. The dynamic behavior and stability of best-docked complex between TRMPRSS2 and proposed molecules were assessed through molecular dynamics (MD) simulation. Several parameters from MD simulation have suggested the stability between the protein and ligands. Binding free energy of each molecule calculated through MM-GBSA approach from the MD simulation trajectory suggested strong affection toward the TMPRSS2. Hence, proposed molecules might be crucial chemical components for the TMPRSS2 inhibition.

Identification of potential anti-TMPRSS2 natural products through homology modelling, virtual screening and molecular dynamics simulation studies.

Recent outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a pandemic of COVID-19. The absence of a therapeutic drug and vaccine is causing severe loss of life and economy worldwide. SARS-CoV and SARS-CoV-2 employ the host cellular serine protease TMPRSS2 for spike (S) protein priming for viral entry into host cells. A potential way to reduce the initial site of SARS-CoV-2 infection may be to inhibit the activity of TMPRSS2. In the current study, the three-dimensional structure of TMPRSS2 was generated by homology modelling and subsequently validated with a number of parameters. The structure-based virtual screening of Selleckchem database was performed through 'Virtual Work Flow' (VSW) to find out potential lead-like TMPRSS2 inhibitors. Camostat and bromhexine are known TMPRSS2 inhibitor drugs, hence these were used as control molecules throughout the study. Based on better dock score, binding-free energy and binding interactions compared to the control molecules, six molecules (Neohesperidin, Myricitrin, Quercitrin, Naringin, Icariin, and Ambroxol) were found to be promising against the TMPRSS2. Binding interactions analysis revealed a number of significant binding interactions with binding site amino residues of TMPRSS2. The all-atoms molecular dynamics (MD) simulation study indicated that all proposed molecules retain inside the receptor in dynamic states. The binding energy calculated from the MD simulation trajectories also favour the strong affinity of the molecules towards the TMPRSS2. Proposed molecules belong to the bioflavonoid class of phytochemicals and are reported to possess antiviral activity, our study indicates their possible potential for application in COVID-19.Communicated by Ramaswamy H. Sarma.