Severe acute respiratory syndrome has relapsed recently as novel coronavirus causing a life threat to the entire world in the absence of an effective therapy. To hamper the replication of the deadly SARS CoV-2 inside the host cells, systematic in silico virtual screening of total 267,324 ligands from Asinex EliteSynergy and BioDesign libraries has been performed using AutoDock Vina against RdRp. The molecular modeling studies revealed the identification of twenty-one macrocyclic hits ( 2 - 22 ) with better binding energy than remdesivir ( 1 ), marketed SARS CoV-2 inhibitor. Further, the analysis using rules for drug-likeness and their ADMET profile revealed the candidature of these hits due to superior oral bioavailability and druggability. Further, the MD simulation studies of top two hits ( 2 and 3 ) performed using GROMACS 2020.1 for 10 ns revealed their stability into the docked complexes. These results provide an important breakthrough in the design of macrocyclic hits as SARS CoV-2 RNA replicase inhibitor.

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Tuberculosis (TB), an airborne disease caused by Mycobacterium tuberculosis, has infected millions of people and been responsible for their deaths. Toward the anti‐TB endeavor, the synthesis of total twenty‐four indole‐2‐carboxamide derivatives as potent anti‐TB agents have been carried out using CDI‐mediated amidation. The biological evaluation against H37Rv revealed compounds 5d, 5e and 5u with MICs in the range of 3.125‐12.5 μg/mL using MABA assay. Further, compound 5u was tested against RAW 264.7 cell by MTT assay and showed 32 % growth inhibitions. The structure activity relationship of the indole‐2‐carboxamides has been established for antimycobacterial activity. The physicochemical properties and ADMET parameters of the 5d, 5e and 5u using pKCSM and SwissADME revealed their suitability as promising drug candidates. Molecular docking studies using AutoDock Vina revealed binding of 5u with the catalytic site of mmpL3 (PDB ID: 6AJG). The MD simulations of the most active compound 5u using GROMACS 2020.1 revealed its stability at the protein active site. Further optimization of indole‐2‐carboxamies may reveal the potentiation of identified anti‐mycobacterial drug candidates.

In the absence of efficient anti-viral medications, the coronavirus disease 2019 (COVID-19), stemming from severe acute respiratory syndrome coronavirus-2 (SARS CoV-2), has spawned a worldwide catastrophe and global emergency. Amidst several anti-viral targets of COVID-19, spike glycoprotein has been recognized as an essential target for the viral entry into the host cell. In the search of effective SARS CoV-2 inhibitors acting against spike glycoprotein, the virtual screening of 175,851 ligands from the 2020.1 Asinex BioDesign library has been performed using in silico tools like SiteMap analysis, pharmacophore-based screening, molecular docking using different levels of precision, such as high throughput virtual screening, standard precision and extra precision, followed by absorption, distribution, metabolism, excretion and toxicity analysis, and molecular dynamics (MD) simulation. Following a molecular docking study, seventeen molecules (with a docking score of less than − 6.0) were identified having the substantial interactions with the catalytic amino acid and nucleic acid residues of spike glycoprotein at the binding site. In investigations using MD simulations for 10 ns, the hit molecules ( 1 and 2 ) showed adequate compactness and uniqueness, as well as satisfactory stability. These computational research findings have offered a key starting point in the field of design and development of novel SARS CoV-2 entry inhibitors with appropriate drug likeliness. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11030-022-10394-9.

Being attracted with their cardiotonic, antidiabetic, cough relieving activity, treatment of fever, absorbent, anti-asthmatic, etc. activities reported in ancient Ayurvedic literature, phytochemicals of Onosma bracteata wall should be evaluated for their activity against SARS-CoV-2 virus. The main objective of this study is to identify a hit molecule for the inhibition of entry, replication, and protein synthesis of SARS CoV-2 virus into the host. To achieve given objective, computational virtual screening of phytochemicals of Onosma bracteata wall has been performed against three main viral targets: spike, RdRp, and M pro . Further, the analysis of Lipinski’s Ro5 and their estimation of ADMET profiles were performed using computational tools. The MD simulations studies of top hits against each viral target have also been performed for 20 ns to ensure their stability. The analysis of results revealed that Pulmonarioside C ( 9 ) and other plant compounds showed better binding affinity towards targets than existing antiviral compounds, making them probable lead compounds against SARS-CoV-2. Structural modifications and studies through in silico analysis provided the founding stone for the establishment of SARS CoV-2 inhibitory potential of phytoconstitutents of Onosma bracteata wall.