ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

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

Shabbir Muhammad, Mahnoor Qaisar, Javed Iqbal, Rasheed Ahmad Khera, Abdullah G. Al-Sehemi, Saleh S. Alarfaji, and Muhammad Adnan

Department of Chemistry, College of Science, King Khalid University, Abha, Saudi Arabia

E-mail: mshabbir@kku.edu.sa

Received: 18 September 2021  Accepted: 23 November 2021

Abstract:

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, \(\pi\)–sigma, \(\pi\)–\(\pi\) T shaped and \(\pi\)-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\(\alpha\) 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.

Graphical abstract

Keywords: Non-structural protein; Mangrove actinomycetes; Molecular docking; Quantum chemistry; Molecular dynamics

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-021-01997-x

Chemical Papers 76 (5) 3051–3064 (2022)