The coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. This virus has a high mismatch repair proofreading ability due to its unique exonuclease activity, making it knotty to treat. The nucleocapsid protein can serve as a potential antiviral drug target, as this protein is responsible for multiple captious functions during the viral life cycle. Herein, we have investigated the potential to repurpose active antiviral compounds of plant origins for treating the SARS-CoV-2 infection. In the present study, we followed the molecular docking methodology to screen druggable natural plants' active compounds against the nucleocapsid protein of SARS-CoV-2. The virtual screening of all 68 compounds revealed that the top seven active compounds, such as withanolide D, hypericin, silymarin, oxyacanthine, withaferin A, Acetyl aleuritolic acid, and rhein, exhibit good binding affinity with druggable ADME properties, toxicity, and Pass prediction. The stability of the docked complexes was studied by conducting molecular simulations of 100 ns. MM-GBSA calculated the binding free energy uncovered that withanolide D, hypericin, and silymarin result in highly stable binding conformations in three different sites of the nucleocapsid protein. However, further investigation is needed in order to validate the candidacy of these inhibitors for clinical trials.Communicated by Ramaswamy H. Sarma.

Erratum in J Biomol Struct Dyn. 2022 Feb 11;:1-2.

Apart from chemical and allopathic drugs, several medicinal plants contain phytochemicals that are potentially useful to counter the COVID-19 pandemic. Withania somnifera (Ashwagandha), which has a good effect on some viral infections, can be considered as a candidate against the virus. In the present study, thirty-nine natural compounds of Ashwagandha were investigated in terms of their binding to the important drug targets to treat the COVID-19. Although the molecular docking calculations reveal the binding affinities of the compounds to Mpro, TMPRSS2, NSP15, PLpro, Spike RBD + ACE2, RdRp and NSP12 as targets in controlling the coronavirus enzymes, Withanoside II is expected to be the most effective compound due to the high affinity in binding with many of considered targets. Furthermore, the Withanoside III, IV, V, X, and XI have favorable binding affinities as ligands with respect to the MM/GBSA calculations. The molecular dynamics simulations MD explore a stable hydrogen bond network between ligands and the active sites residues. Also, the dynamic fluctuations of the binding site residues verify their tight binding to ligands. Moreover, the stability of ligand-protein complexes is approved by the RMSD ranges lower than 0.5 Å in equilibration zone for all mentioned complexes. The TMPRSS2-Withanolide Q and Mpro-Withanoside IV complexes are the most stable pairs using the MM/GBSA calculations and MD simulation.Communicated by Ramaswamy H. Sarma.

Dengue virus is part of the flaviviruses that spread through the Aedes mosquito species and causes vascular leakage and multiple organ failure. The non-structural protein 1 (NS1) is involved in the replication of Dengue virus. The glycosylated dimeric and hexameric form of NS1 is the biologically active form. Therefore, in this study, the NS1 protein was modeled in dimeric form which is predominantly present inside the host cell. The dimeric model was validated and it was glycosylated at ASN130 and ASN207 with oligomannose. This model was simulated for 100 ns to retrieve the global minima structure. The andrographolide and its four derivatives were docked non-specifically against the dimeric glycosylated NS1 protein. The neo-andrographolide compound showed strong interactions with favorable binding energy of -8.2 kcal/mol and electrostatic binding affinity of -8.9 kcal/mol. All docked ligand-protein complexes were simulated for 100 ns. The molecular dynamics simulation analysis comprising of root mean square deviation and fluctuation, the radius of gyration, hydrogen bonding, potential energy, principal component analysis, SASA, DSSP, Free energy Landscape, MM-PBSA and Electrostatic binding affinity revealed about the stability of complex systems. These andrographolide and its derivatives was found to be interacting with Lys14 and this residue was reported as one of the important residues in NS1 activity. Among all compounds, the neo-andrographolide compound has the promising potential to inhibit the activity of the NS1 which is necessary for the Dengue virus replication.Communicated by Ramaswamy H. Sarma.

In this report, synthesis, characterization, biological and molecular modeling studies of Nophen Schiff base [N,N-bis(2-hydroxy-1-naphthaldehyde)-o-phenylenediamine] and Co(II)-Nophen complex have been furnished. BSA binding affinities of the ligand and Co(II)-Nophen complex have been appraised by UV-visible, fluorescence and cyclic voltammetric techniques. Spectroscopic measurements indicate strong binding of the complex with BSA protein through static quenching mechanism with binding constant in the order of 104 M-1. The negative shift of the peak potential in cyclic voltammetry suggested an electrostatic interaction. Molecular docking analysis reveals significant binding affinity (-6.3 kcal/mol) of the complex towards BSA protein. It is amazing that the in vitro cytotoxicity of Co(II)-Nophen complex against A549 cell lines (Human lung carcinoma cells) has remarkable potentials with 29 ± 1.2 µM as IC50 value. Comparing the biological activity towards microorganisms, Co(II)-Nophen complex show substantial response than the Nophen ligand.Communicated by Ramaswamy H. Sarma.

Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant tuberculosis (MDR-TB) is a leading cause of severe hospital and infection-related morbidity and mortality in the general population. There is a critical need for dynamic, powerful medication candidates to combat MRSA and MDR-TB infections in this specific setting. As a result, the current research focuses on the development of novel sulfathiazole derivative compounds that could be used as anti-MRSA and anti-MDR-TB agents. Virtual screening approaches were used to identify the potential lead sulfathiazole derivatives with the help of BIOVIA Discovery Studio 2017 software. In this in silico study, 10 novel sulfathiazole derivatives were virtually screened from 74 designed compounds. These 10 compounds had the best predictive docking scores in MRSA and MDR-TB receptors and were then put through a molecular dynamics simulation to explain protein stability, ligand characteristics and protein-ligand interactions. The Lipinski rule and ADMET prediction results also suggested that 11 compounds (mol-12, mol-22, mol-23, mol-28, mol-30, mol-32, mol-34, mol-35, mol-45 and mol-47) have strong drug similarity features. Our findings imply that the 10 novel sulfathiazole compounds studied could be viable new therapeutic leads for MRSA and MDR-TB.

Comment on J Biomol Struct Dyn. 2021 Nov;39(18):7168-7180.