Inhibitory Potential of Chitosan Derivatives against Severe Acute Respiratory Syndrome Coronavirus 2: An In Silico Prospective

Abstract

The present work was designed to investigate the antiviral potential of novel monomeric and oligomeric chitosan derivatives through in silico approaches. The goal was to identify potent broad-spectrum antiviral compounds as promising drug candidates against severe acute respiratory syndrome coronavirus 2 and understand their mode of action. Chitosan biopolymer and its derivatives were virtually screened against the spike glycoprotein and human angiotensin-converting enzyme 2 (ACE2) receptor of novel coronavirus-19. Hydroxypropyl trimethyl ammonium chloride chitosan (HTCC), a polymeric chitosan, has been reported to interact with the corona viral spike (S) protein and blocks its interaction with the ACE2 receptor. The enhancement of antiviral activity relies on better biocompatibility, structural correlations, variation in the degree of deacetylation, and molecular weight of modified chitosan derivatives. The chitosan derivatives constructively interact with viral S protein. Among the chitosan derivatives, N-carboxymethyl chitosan (NCMC) displayed efficient binding affinity. Comparing NCMC to mHTCC, monomeric chitosan, for their interaction with the S protein, receptor binding domain site, and ACE2 receptor, NCMC displayed better binding affinity of −7.9, −6.3, and −7.4 with binding energies of −6.2, −4.8, and −5.5 kcal/mol, respectively. Furthermore, through flexible docking, the interactions of the S protein with ACE2 receptor and ligand mHTCC-S protein complex and NCMC-S protein complex with ACE2 receptor were calculated, showing an efficient reduction of binding energy from −901.2 kJ/mol to −765.06 kJ/mol and −814.72 kJ/mol, respectively. This points to the decrease binding affinity of the viral S protein for the ACE2 receptor in the presence of NCMC/mHTCC. For the first time, the computational study envisages the antiviral efficiency of NCMC, mHTCC, and biocompatible chitosan derivatives as a preventive intervention against COVID-19.