Insighting isatin derivatives as potential antiviral agents against NSP3 of COVID-19.

The world is now facing intolerable damage in all sectors of life because of the deadly COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2. The discovery and development of anti-SARS-CoV-2 drugs have become pragmatic in the time needed to fight against this pandemic. The non-structural protein 3 is essential for the replication of transcriptase complex (RTC) and may be regarded as a possible target against SARS-CoV-2. Here, we have used a comprehensive in silico technique to find potent drug molecules against the NSP3 receptor of SARS-CoV-2. Virtual screening of 150 Isatin derivatives taken from PubChem was performed based on their binding affinity estimated by docking simulations, resulting in the selection of 46 ligands having binding energy greater than -7.1 kcal/mol. Moreover, the molecular interactions of the nine best-docked ligands having a binding energy of ≥ -8.5 kcal/mol were analyzed. The molecular interactions showed that the three ligands (S5, S16, and S42) were stabilized by forming hydrogen bonds and other significant interactions. Molecular dynamic simulations were performed to mimic an in vitro protein-like aqueous environment and to check the stability of the best three ligands and NSP3 complexes in an aqueous environment. The binding energy of the S5, S16, and S42 systems obtained from the molecular mechanics Poisson-Boltzmann surface area also favor the system's stability. The MD and MM/PBSA results explore that S5, S16, and S42 are more stable and can be considered more potent drug candidates against COVID-19 disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02298-7.

Insighting the Therapeutic Potential of Fifty (50) Shogaol Derivatives Against Mpro of SARS-CoV-2

SARS-CoV-2, which causes COVID-19 disease, has proven to be a disastrous pandemic due to its contagious nature. This study has been planned to theoretically explore some antidotes against this virus from natural compounds. A total of 150 compounds from the shogaol class and shogaol derivatives (SDs) have been screened whereas 50 among those, which obeyed Lipinski’s Rule of Five (Ro5), have further been investigated using molecular docking techniques. Furthermore, reference antiviral drug chloroquine (ChQ) and Co-Crystallized inhibitor have also been studied against Mpro of SARS-CoV-2 for comparing the potential of our docked ligands. Surprisingly, 78% of our docked ligands have shown binding energies and inhibition constants lower than ChQ and all ligands showed these values lower than an inhibitor. We further visualized the nature of intermolecular interactions for the best docked six ligands, which have shown higher binding affinities. We have also assessed ADMET properties for three ligands that displayed visually the best intermolecular interactions. Quantum analysis of three selected ligands L4, L5, and L9 has proved their reactivity and kinetic stability. Moreover, molecular dynamic simulations over 60ns have been run for free Mpro and its selected three ligand-protein complexes for evaluating conformational stability and residual flexibility of docked complexes. Furthermore, 100ns the MD simulations have been performed for two ligand complexes L4, L5 (with negative binding free energy), and inhibitor. Available parameters suggest stable complexes for our ligands and could be active drugs against SARS-CoV-2 in near future. [ FROM AUTHOR] Copyright of Journal of Computational Biophysics & Chemistry is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Isolation of Thioinosine and Butenolides from a Terrestrial Actinomycetes sp. GSCW-51 and Their in Silico Studies for Potential against SARS-CoV-2.

In our continuous screening for bioactive microbial natural products, the culture extracts of a terrestrial Actinomycetes sp. GSCW-51 yielded two new metabolites, i. e., 5-hydroxymethyl-3-(1-hydroxy-6-methyl-7-oxooctyl)dihydrofuran-2(3H)-one (1), 5-hydroxymethyl-3-(1,7-dihydroxy-6-methyloctyl)dihydrofuran-2(3H)-one (2), and two known compounds; 5'-methylthioinosine (3), and 5'-methylthioinosine sulfoxide (4), which are isolated first time from any natural source, along with four known compounds (5-8). The structures of the new compounds were deduced by HR-ESI-MS, 1D and 2D NMR data, and in comparison with related compounds from the literature. Additionally, owing to the current COVID-19 pandemic situation, we also computationally explored the therapeutic potential of our isolated compounds against SARS-CoV-2. Compound 4 showed the best binding energies of -6.2 and -6.6 kcal/mol for Mpro and spike proteins, respectively. The intermolecular interactions were also studied using 2-D and 3-D imagery, which also supported the binding energies as well as put several insights under the spotlight. Furthermore, Lipinski's rule of 5 was used to predict the drug likeness of compounds 1-4, which indicated all compounds obey Lipinski's rule of 5. The study of bioavailability radars of the compounds 1-4 also confirmed their drug likeness properties where all the five crucial drug likeness parameters are in color area, which is safe to be used as drugs. Our isolation and computational findings highly encourage the scientific community to do further in vitro and in vivo studies of compounds 1-4.

Exploring the inhibitory potential of novel bioactive compounds from mangrove actinomycetes against nsp10 the major activator of SARS-CoV-2 replication.

The current study reveals the inhibitory potential of novel bioactive compounds of mangrove actinomycetes against nsp10 of SARS-CoV-2. A total of fifty (50) novel bioactive (antibacterial, antitumor, antiviral, antioxidant, and anti-inflammatory) compounds of mangrove actinomycetes from different chemical classes such as alkaloids, dilactones, sesquiterpenes, macrolides, and benzene derivatives are used for interaction analysis against nsp10 of SARS-CoV-2. The six antiviral agents sespenine, xiamycin c, xiamycin d, xiamycin e, xiamycin methyl ester, and xiamycin A (obeyed RO5 rule) are selected based on higher binding energy, low inhibition constant values, and better-docked positions. The effective hydrogen and hydrophobic (alkyl, π -sigma, π - π T shaped and π -alkyl) interaction analysis reveals the four antivirals sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are supposed to be the most auspicious inhibitors against nsp10 of SARS-CoV-2. Quantum chemistry methods such as frontier molecular orbitals and molecular electrostatic potential are used to explain the thermal stability and chemical reactivity of ligands. The toxicity profile shows that selected ligands are safe by absorption, distribution, metabolism, excretion, and toxicity profiling and also effective for inhibition of nsp10 protein of SARS-CoV-2. The molecular dynamic simulation investigation of apo and halo forms of nsp10 done by RMSD of C α atoms of nsp10, all amino acid residues RMSF, count total number of hydrogen bonds and radius of gyration (R g). MD simulations reveal the complexes are stable and increase the structural compactness of nsp10 in the binding pocket. The lead antiviral compounds sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are recommended as the most promising inhibitors against nsp10 of SARS-CoV-2 pathogenicity. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-021-01997-x.

Shedding Light on the Synthesis, Crystal Structure, Characterization, and Computational Study of Optoelectronic Properties and Bioactivity of Imine derivatives.

Two imine compounds named as (E)-2-(((3,4-dichlorophenyl)imino)methyl)phenol (DC2H) and (E)-4-(((2,4-dimethylphenyl)imino)methyl)phenol (DM4H) are synthesized, and their crystal structures are verified using the single-crystal X-ray diffraction (XRD) technique. The crystal structures of the compounds are compared with the closely related crystal structures using the Cambridge Structural Database (CSD). The crystal packing in terms of intermolecular interactions is fully explored by Hirshfeld surface analysis. Void analysis is carried out for both compounds to check the strength of the crystal packing. Furthermore, a state-of-the-art dual computational technique consisting of quantum chemical and molecular docking methods is used to shed light on the molecular structure, optoelectronic properties, and bioactivity of indigenously synthesized compounds. The optimized molecular geometries are compared with their counterpart experimental values. Based on previous reports of biofunctions of the indigenously synthesized imine derivatives, they are explored for their potential inhibition properties against two very crucial proteins (main protease (Mpro) and nonstructural protein 9 (NSP9)) of SARS-CoV-2. The calculated interaction energy values of DC2H and DM4H with Mpro are found to be -6.3 and -6.6 kcal/mol, respectively, and for NSP9, the calculated interaction energy value is found to be -6.5 kcal/mol. We believe that the current combined study through experiments and computational techniques will not only pique the interest of the broad scientific community but also evoke interest in their further in vitro and in vivo investigations.

Identification of Marine Fungi-Based Antiviral Agents as Potential Inhibitors of SARS-CoV-2 by Molecular Docking, ADMET and Molecular Dynamic Study

The ongoing eruption of the COVID-19 pandemic instigated by severe-acute-respiratory-syndrome-coronavirus 2 (SARS-CoV-2) has produce enormous damage to the world. The need of the hour is to stop this pandemic by inhibiting the main protease (MPro) of SARS-CoV-2, which is primarily involved in viral replication. Our study aims to find potential inhibitors for MPro by docking marine fungi-based 90 antiviral compounds against SARS-CoV-2. Among these, 11 antiviral compounds (obeying Lipinski RO5) are selected from 90 docked antiviral compounds on the basis of binding energy range (−6.4kcal/mol to −9kcal/mol) and low inhibition constant values (0.23μM to 2.5μM) as compared with remdesivir (reference compound) toward MPro of SARS-CoV-2. Tryptoquivaline F, arisugacin B, and arisugacin A antiviral compounds exhibited effective hydrogen and hydrophobic (alkyl, π-alkyl, and π-anion) interactions and are expected to be potential protease inhibitors. Drug-likeness of these lead compounds are elaborated by boiled-egg and bioavailability radar map. The toxicity profile showed that the lead compounds L1, L2, and L3 have no AMES toxicity, skin sensitization, and cardiac toxicity. The RMSD graph proposed that all the complexes, i.e. L1, L2, and L3 are in the adequate RMSD range with the average value of 2.1Å. All the complex systems of L1, L2, and L3 showed fluctuations in the acceptable RMSF range of 1.5Å to 3Å. The molecular dynamics simulation proved the stability of docked complexes L1, L2, and L3 in the binding pocket of main protease. The average hydrogen count of all complexes is L1=69.5, L2=67.7, and L3=68.6 H-bonds. The complexes L1-MPro, L2-MPro, and L3-MPro have an average value of Rg as 22.44Å, 22.63Å, and 22.50Å, respectively. The lead compounds L1 (tryptoquivaline F), L2 (arisugacin b), and l3 (arisugacin A) in this study are the most promising inhibitors of SARS-CoV-2 main protease MPro, which are not reported in ealier studies. Our findings will evoke the scientific interest for their further in vitro and in vivo experimental studies. [ FROM AUTHOR] Copyright of Journal of Computational Biophysics & Chemistry is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Synthesis, characterization, and computational study of copper bipyridine complex [Cu (C18H24N2) (NO3)2] to explore its functional properties.

In the present study, copper (II) complex of 4, 4'-di-tert-butyl-2,2'-bipyridine [Cu (C18H24N2) (NO3)2], 1 is investigated through its synthesis and characterization using elemental analysis technique, infra-red spectroscopy, and single-crystal analysis. The compound 1 crystallizes in orthorhombic space group P212121. The copper atom in the mononuclear complex is hexa coordinated through two nitrogen and four oxygen atoms from bipyridine ligand and nitrate ligands. The thermal analysis depicts the stability of the entitled compound up to 170 °C, and the decomposition takes place in different steps between 170 and 1000 °C. Furthermore, quantum chemical techniques are used to study optoelectronic, nonlinear optical, and therapeutic bioactivity. The values of isotropic and anisotropic linear polarizabilities of compound 1 are calculated as 41.65 × 10-24 and 23.02 × 10-24 esu, respectively. Likewise, the static hyperpolarizability is calculated as 47.92 × 10-36 esu using M06 functional compared with para-nitroaniline (p-NA) and found several times larger than p-NA. Furthermore, the antiviral potential of compound 1 is studied using molecular docking technique where intermolecular interactions are checked between the entitled compound and two crucial proteins of SARS-CoV-2 (COVID-19). Our investigation indicated that compound 1 interacts more vigorously to spike protein than main protease (MPro) due to its better binding energy of -9.60 kcal/mol compared with -9.10 kcal/mol of MPro. Our current study anticipated that the above-entitled coordination complexes could be potential candidates for optoelectronic properties and their biological activity.

Experimental and computational study of naphthalimide derivatives: Synthesis, optical, nonlinear optical and antiviral properties.

The nonlinear optical (NLO) and antiviral properties of naphthalimide Schiff base compounds (5a-c) were experimentally and computationally investigated. The synthesized compounds (5a-c) were successfully characterized via UV-Vis, FTIR, 1H NMR, fluorescence spectroscopy, and elemental analysis. The calculated average third-order NLO polarizabilities (˂γ˃) of 5a, 5b, and 5c were found to be 5, 9, and 21 times greater than the ˂γ˃ amplitude of p-NA, respectively. The computed results revealed the potential of the synthesized compounds for NLO applications. Additionally, molecular docking studies of the synthesized compounds with two crucial SARS-CoV-2 proteins were performed to examine their biochemical properties. Compound 5c exhibited a higher binding affinity with the spike protein compared to that with Mᴾᴿᴼ. The results obtained herein indicate the potential of the synthesized naphthalimide derivatives for optoelectronic and drug design applications.