Chitosan derivatives: A suggestive evaluation for novel inhibitor discovery against wild type and variants of SARS-CoV-2 virus.

With increasing global cases and mortality rates due to COVID-19 infection, finding effective therapeutic interventions has become a top priority. Marine resources are not explored much and to be taken into consideration for exploring antiviral potential. Chitosan (carbohydrate polymer) is one such bioactive glycan found ubiquitously in marine organisms. The presence of reactive amine/hydroxyl groups, with low toxicity/allergenicity, compels us to explore it against SARS-CoV-2. We have screened a library of chitosan derivatives by site-specific docking at not only spike protein Receptor Binding Domain (RBD) of wild type SARS-CoV-2 but also on RBD of B.1.1.7 (UK) and P.1 (Brazil) SARS-CoV-2 variants. The obtained result was very interesting and ranks N-benzyl-O-acetyl-chitosan, Imino-chitosan, Sulfated-chitosan oligosaccharides derivatives as a potent antiviral candidate due to its high binding affinity of the ligands (-6.0 to -6.6 kcal/mol) with SARS-CoV-2 spike protein RBD and they critically interacting with amino acid residues Tyr 449, Asn 501, Tyr 501, Gln 493, Gln 498 and some other site-specific residues associated with higher transmissibility and severe infection. Further ADMET analysis was done and found significant for exploration of the future therapeutic potential of these three ligands. The obtained results are highly encouraging in support for consideration and exploration in further clinical studies of these chitosan derivatives as anti-SARS-CoV-2 therapeutics.