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.

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.)