Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a member of the Coronaviridae family, causing major destructions to human life directly and indirectly to the economic crisis around the world. Although there is significant reporting on the whole genome sequences and updated data for the different receptors are widely analyzed and screened to find a proper medication. Only a few bioassay experiments were completed against SARS-CoV-2 spike protein. We collected the compounds dataset from the PubChem Bioassay database having 1786 compounds and split it into the ratio of 80–20% for model training and testing purposes, respectively. Initially, we have created 11 models and validated them using a fivefold validation strategy. The hybrid consensus model shows a predictive accuracy of 95.5% for training and 94% for the test dataset. The model was applied to screen a virtual chemical library of Natural products of 2598 compounds. Our consensus model has successfully identified 75 compounds with an accuracy range of 70–100% as active compounds against SARS-CoV-2 RBD protein. The output of ML data (75 compounds) was taken for the molecular docking and dynamics simulation studies. In the complete analysis, the Epirubicin and Daunorubicin have shown the docking score of −9.937 and −9.812, respectively, and performed well in the molecular dynamics simulation studies. Also, Pirarubicin, an analogue of anthracycline, has widely been used due to its lower cardiotoxicity. It shows the docking score of −9.658, which also performed well during the complete analysis. Hence, after the following comprehensive pipeline-based study, these drugs can be further tested in vivo for further human utilization. Communicated by Ramaswamy H. Sarma

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is one of the rapid spreading coronaviruses that belongs to the Coronaviridae family. The rapidly evolving nature of SARS-CoV-2 results in a variety of variants with a capability of evasion to existing therapeutics and vaccines. So, there is an imperative need to discover potent drugs that can able to disrupt the function of multiple drug targets to tackle the SARS-CoV-2 menace. Here in this study, we took the different targets of SARS-CoV-2 prepared in the Schrodinger maestro. The library of the DrugBank database is screened against the selected crucial targets. Our molecular docking, Molecular Mechanics/Generalized Born Surface Area (MMGBSA), and molecular dynamics simulation studies led to identifying dinaciclib and theodrenaline as potential drugs against multiple drug targets: main protease, NSP15-endoribonuclease and papain-like-protease, of SARS-CoV-2. Dinaciclib with papain-like protease and NSP15-endoribonuclease show the docking score of −7.015 and −8.737, respectively, while the theodrenaline with NSP15-endoribonuclease and main protease produced the docking score of −8.507 and −7.289, respectively. Furthermore, the binding free energy calculations with MM/GBSA and molecular dynamics simulation studies of the complexes confirm the reliability of the drugs. The selected drugs are capable of binding to multiple targets simultaneously, thus withstanding their activity of target disruption in different variants of SARS-CoV-2. Although, the repurposed drugs are showing potent activity, but may need further in-vitro and in-vivo validations. Communicated by Ramaswamy H. Sarma

Aromatase enzyme plays a fundamental role in the development of estrogen receptors, and due to this functionality, the enzyme has gained significant attention as a therapeutic for reproductive disorders and cancer diseases. The currently employed aromatase inhibitors have severe side effects whereas our novel aromatase inhibitor is more selective and less toxic, therefore has greater potential to be developed as a drug. The research framework of this study is to identify a potent inhibitor for the aromatase target by profiling molecular descriptors of the ligand and to find a functional pocket in the target by docking and MD simulations. For assessing cellular and metabolic activities as indicators of cell viability and cytotoxicity, in-vitro studies were performed by using the colorimetric MTT assay. Aromatase activities were determined by a fluorometric method. Cell morphology was assessed by phase-contrast light microscopy. Flow cytometry and Annexin V-FITC/PI staining assay determined cell cycle distribution and apoptosis. This study reports that CHEMBL708 (Ziprasidone) is the most promising compound that showed excellent aromatase inhibitory activity. By using better drug design methods and experimental studies, our study identified a novel compound that could be effective as a high-potential drug candidate against aromatase enzyme. We conclude that the compound ziprasidone effectively blocks the cell cycle at the G1-S phase and induces cancer cell death. Further, in-vivo studies are vital for developing ziprasidone as an anticancer agent. Lastly, our research outcomes based on the results of the in-silico experiments may pave the way for identifying effective drug candidates for therapeutic use in breast cancer.

Angiotensin converting enzyme 2 (ACE2) and main protease (M^Pro) are significant target proteins, mainly involved in the attachment of viral genome to host cells and aid in replication of severe acute respiratory syndrome‐coronaviruses or SARS‐CoV genome. In the present study, we identified 11 potent bioactive compounds from ethanolic leaf extract of Ipomoea obscura (L.) by using GC‐MS analysis. These potential bioactive compounds were considered for molecular docking studies against ACE2 and M^Pro target proteins to determine the antiviral effects against SARS‐COV. Results exhibits that among 11 compounds from I. obscura (L.), urso‐deoxycholic acid, demeclocycline, tetracycline, chlorotetracycline, and ethyl iso‐allocholate had potential viral inhibitory activity. Hence, the present findings suggested that chemical constitution present in I. obscura (L.) will address inhibition of corona viral replication in host cells.

Transcription factor NAM-B1 has a major role in the process of senescence, which results in higher Fe and Zn concentrations in grains of wild wheat (T. durum; Td). The absence of the wild type NAMB1 in T. aestivum (Ta), one of the cardinal crops essential for more than 1/3^rd of the global population, affects Fe and Zn remobilisation to the maturing grain from the flag leaf resulting in lesser micronutrient bioavailability. The cardinal difference in the NAMB1 gene between the two species is the absence of +1bp allele in Ta. Insilico studies using NAMB1 from Td and Ta was performed to explore the variation in the interaction with the conserved cis-element DNA motif (CATGTG) as both the proteins share the same domain, but there are no in silico studies reported of these proteins. The secondary structure, 3d-modelling of the proteins, DNA-protein docking and dynamics have computed by Schrodinger Prime Suite. Predicted secondary structures were energy minimised using Macromodel and docking was performed based on binding energy and hydrogen bonds. Molecular dynamics simulation of NAMB1-Ta and NAMB1-Td individually and with the cis-element motif, performed for 100ns, revealed significant variations in the protein-DNA interaction in Ta. This work provides the modelled 3d-interaction profile caused by a single bp frameshift mutation in understanding the difference in function between NAMB1 orthologs due to lack of NAC domain. The overall computational analysis reveals that NAMB1-Ta and NAMB1-Td proteins display a good amount of dissimilarity in their structure, dynamics and DNA-binding characteristics.