Targeting multidrug resistant Staphylococcus aureus with cationic chlorpromazine-peptide conjugates.

Antimicrobial resistance is a serious public health risk. Its severity is fueled on an unprecedented scale, necessitating the demand for novel antimicrobial scaffolds aimed at novel targets. Herein, we present cationic chlorpromazine peptide conjugates that are rationally intended to targetmultidrug-resistant (MDR) bacteria. The most potent compound, CPWL, of all the conjugates evaluated, showed promising antibacterial activity against clinical, MDR S. aureus, with no cytotoxicity. The molecular docking experiments confirmed that CPWL possessed a very high affinity for S. aureus enoyl reductase (saFabI). Furthermore, CPWL antibacterial action against saFabI was further corroborated by MD simulation studies. Thus, our findings highlight cationic chlorpromazine as a promising scaffold for the development of saFabI inhibitors to target severe staphylococcal infections.

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.

Underscoring the immense potential of chitosan in fighting a wide spectrum of viruses: A plausible molecule against SARS-CoV-2?

Chitosan is a deacetylated polycationic polysaccharide derived from chitin. It is structurally constituted of N-acetyl-D-glucosamine and ß-(1-4)-linked D-glucosamine where acetyl groups are randomly distributed across the polymer. The parameters of deacetylation and depolymerization process greatly influence various physico-chemical properties of chitosan and thus, offer a great degree of manipulation to synthesize chitosan of interest for various industrial and biomedical applications. Chitosan and its various derivatives have been a potential molecule of investigation in the area of anti-microbials especially anti-fungal, anti-bacterial and antiviral. The current review predominantly highlights and discusses about the antiviral activities of chitosan and its various substituted derivatives against a wide spectrum of human, animal, plants and bacteriophage viruses. The extrinsic and intrinsic factors that affect antiviral efficacy of chitosan have also been talked about. With the rapid unfolding of COVID-19 pandemic across the globe, we look for chitosan as a plausible potent antiviral molecule for fighting this disease. Through this review, we present enough literature data supporting role of chitosan against different strains of SARS viruses and also chitosan targeting CD147 receptors, a novel route for invasion of SARS-CoV-2 into host cells. We speculate the possibility of using chitosan as potential molecule against SARS-CoV-2 virus.