3ß-Acetoxy-21α-H-hop-22(29)ene, a novel multitargeted phytocompound against SARS-CoV-2: in silico screening.

The present pandemic disease COVID-19 demands an urgent need for more efficient antiviral drugs against SARS-CoV-2. Computational drug designing and discovery enable us to explore ethnomedicinal plants as a source of various lead molecules that can be used against present and future pathogens. Adiantum latifolium Lam., a common fern, is resistant to pathogens mainly due to the presence of various phytochemicals having antimicrobial properties. In our previous study, 3ß-acetoxy-21α-H-hop-22(29)ene, a terpenoid has been characterized from the methanol extract of leaves of A. latifolium. The manuscript evaluates the antiviral potency of the compound against SARS-CoV-2 through molecular docking method. Proteins essential for SARS-CoV-2 multiplication in host cells are the target sites. The study revealed strong binding affinity of the compound for all the ten proteins selected, including seven nonstructural proteins, two structural proteins and one receptor protein, with a binding energy of -4.67 to -8.76 kcal/mol. MDS and MMPBSA analysis of the best ranked complex further confirmed the results. The multitargeted compound can be considered as a natural lead molecule in drug designing against COVID-19, but requires wet-lab experimentation and clinical trials.Communicated by Ramaswamy H. Sarma.

SPECTRAL CHARACTERIZATION AND BIOLOGICAL STUDIES OF SOME TERNARY COMPLEXES WITH MOLECULAR DOCKING INVESTIGATIONS AGAINST MERS AND SARS TYPE CORONAVIRUSES

A series of ternary complexes with a Schiff base (HL1) derived from 2-hydrazinobenzimidazole and o-hydroxybenzophenone (primary ligand) have been prepared. Here, 1,10-phenanthroline acts as secondary ligand (L2). These metal complexes were investigated by UV-Vis, IR, H-1 NMR and thermal techniques. The spectral data confirmed tridentate nature of the SB ligand with NNO type coordination, whereas the secondary ligand L2 (1,10-phenanthroline) coordinated through its two nitrogen atoms (NN type). These compounds possess distorted octahedral geometry. Moreover, these compounds were screened against B. subtilis and E. coli to evaluate their antibacterial activity. In addition, molecular docking studies were performed against MERS-CoV and SARS-CoV-2 main protease (Mpro). Moreover, DFT calculations and QSAR studies of the SB ligand were also performed.

22-Hydroxyhopane, a novel multitargeted phytocompound against SARS-CoV-2 from Adiantum latifolium Lam.

The present pandemic disease COVID-19 demands an urgent need for more efficient antiviral drugs against SARS-CoV-2. 22-Hydroxyhopane is a bioactive triterpenoid compound with antibacterial activity, present in the leaves of Adiantum latifolium. In this study, molecular docking method revealed strong binding affinity of the compound for ten proteins essential for SARS-CoV-2 multiplication in host cells, including seven nonstructural proteins, two structural proteins and one receptor protein, with a binding energy of -7.61 to -9.82 kcal/mol and inhibition constant <1 µM. MDS and MM-PBSA analysis of the best ranked complex further confirmed the results. The targets selected include six enzymes, RNA binding protein, spike protein, membrane protein and ACE2 receptor of SARS-CoV-2. It is the first report of a natural compound from A. latifolium having multitargeted activity against SARS-CoV-2. We conclude that 22-hydroxyhopane may be used as a best source for the development of novel therapeutic drugs for COVID-19, but requires further evaluations.

Screening of natural compounds from Cyperus rotundus Linn against SARS-CoV-2 main protease (Mpro): An integrated computational approach.

Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that has been spreading across the globe. The World Health Organization (WHO) declared it as a public health emergency. The treatment of COVID-19 has been hampered due to the lack of effective therapeutic efforts. Main Protease (Mpro) is a key enzyme in the viral replication cycle and its non-specificity to human protease makes it a potential drug target. Cyperus rotundus Linn, which belongs to the Cyperaceae family, is a traditional herbal medicine that has been widely studied for its antiviral properties. In this study, a computational approach was used to screen natural compounds from C. rotundus Linn using BIOVIA Discovery Suite and novel potential molecules against Mpro of SARS-CoV-2 were predicted. Molecular docking was performed using LibDock protocol and selected ligands were further subjected to docking analysis by CDOCKER. The docking scores of the selected ligands were compared with standard antiretroviral drugs such as lopinavir and ritonavir to assess their binding potentials. Interaction pharmacophore analysis was then performed for the compounds exhibiting good binding scores to evaluate their protein-ligand interactions. The selected protein-ligand complexes were subjected to molecular dynamics simulation for 50 ns. Results of binding free energy analysis revealed that two compounds-ß-amyrin and stigmasta-5,22-dien-3-ol-exhibited the best binding interactions and stability. Finally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were performed to understand the pharmacokinetic properties and safety profile of the compounds. The overall results indicate that the phytochemicals from Cyperus rotundus Linn, namely ß-amyrin and stigmasta-5,22-dien-3-ol, can be screened as potential inhibitors of SARS-CoV-2 Mpro.