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PurposeMucorales has been described to be widely distributed during the most recent COVID-19 pandemic, with a greater frequency of disease in India, particularly among those with immune deficiencies. This study aims to use computational tools to develop a vaccine.Design/methodology/approachThe authors investigated at Mucorales proteins that had previously been associated to virulence factors. Recent research suggests that a vaccine based on high-level cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) and B-cell lymphocyte (BCL) epitopes from diverse proteins might be developed. Furthermore, the vaccine assembly contains the targeted epitopes as well as PADRE peptides to induce an immune response. Computational approaches were used to analyze the immunological parameters used to build the suggested vaccine and validate its TLR-3 binding.FindingsThese studies show that the vaccination is capable of triggering a particular immune response. The authors offer a technique for developing and evaluating candidate vaccines using computational tools. To the best of their knowledge, this is the first immunoinformatic research of a prospective mucormycosis vaccine.Originality/valueDuring this audit, a successful attempt was made to create a subunit MEV against black fungus. In the current study, MEV has been proposed as a suitable neutralizer candidate since it is immunogenic, secure, stable and interacts with human receptors. A stream study, on the other hand, is produced via a mixed vaccinosis approach. Following that, vaccinologists may perform more exploratory testing to evaluate whether the vaccine is effective.

A novel series of fluoro/methoxy indole analogues 6 was synthesized and the final targets were confirmed by IR, 1H & 13C NMR and mass spectral analysis. Novel 3-substituted indole derivatives estimate for their antibacterial, antioxidant activities particularly the parent core combined with benzamides ring significantly. From antibacterial activities, compounds 6c, 6e and 6b show the highest bacterial activity against S. epidermidis, S. aureus, E. coli, with zone of inhibition 34, 30, 28 mm, respectively. Novel fluoroindole derivatives 6c, 6b, 6i shows an excellent antioxidant activity with % of inhibition 150.12, 139.04, 137.08 mmol/mL, respectively. The calculations for ligand-protein flexible of crystal structure of C(30) carotenoid dehydrosqualene synthase from S. aureus complexed with bisphosphonate BPH-700 (2ZCS). Among the designed compounds 6c exhibited highest hydrogen bonding interactions 2.06 Å, 1.85 Å with amino acids Asp27, Lys273 and binding energy -6.38 kcal/ mol, respectively. Fluoroindoles 6i, 6e and 6f shows highest ΔG = -7.90, -7.66, -7.47 kcal/mol with dissociation constants 10.32, 21.77, 22.68 μM and amino acid Lys273 interactions.

Introduction: Progress in the development of triazolyl-oxadiazoles is a bisphosphonate-700 inhibitor is still continuing with an outcome of the good scaffold as oxadiazole as well as triazoles individually for antibacterial activity. Hence, we proposed a suitable approach for the synthesis of dual heterocyclic analogues consisting of the therapeutically used non steroidal anti-inflammatory drugs in a combined form and evaluated for their antibacterial, antifungal activities, docking studies. Methods: The chemical structures were confirmed by various spectroscopic methods like IR, 1H NMR, 13C NMR, mass, and elemental analysis. The antibacterial, antifungal activity of these compounds was screened against Gram-positive, Gram-negative bacteria and fungal stains by agar well diffusion method. The crystal structure of S. aureus complexed with active site of bisphosphonate BPH-700 (2ZCS) was obtained from the Protein Database (PDB, http://www.rcsb.org). Molecular properties, drug likeness score, lipophilicity and solubility parameters by Molinspiration and Molsoft software. 7f (2-NO2, 5-Ome), 7g (3-Cl, 4-Cl), 7a (2-NO2) Results: Among the synthesised NSAID-triazolyl-oxadiazole containing 2-nitro-5-methoxy (7f), 3,4-dichloro (7g) derivatives were found to be high active antibacterial agents against S. aureus, E. coli with MICs 16, 19 μg/mL respectively. 2-nitro-5-methoxy (7f), 4-bromo (7h) and 2-nitro (7a) derivatives displayed superior antifungal activity against A. niger and MICs 56, 76, 130 μg/mL respectively. From molecular docking NSAID linked to 3,4-dichloro analogue (7g) revealed stronger binding interaction (ΔG =7.90 Kcal/Mol) with amino acids Asp49 (1.19 A˚), Arg45 (2.17 A˚), Lys17, Lys46 in the active site of S. aureus complexed with bisphosphonate Bph-700 (2ZCS). The compounds followed the Lipinski ‘Rule of five’ were synthesized for antimicrobial screening as oral bioavailable drugs/leads. Maximum drug likeness model score 0.49, 0.41 was found for compounds 7h, 7b. Conclusion: The present work, through simple synthetic approaches, led to the development of novel hybrids of triazole-oxadiazole pharmacophores that exhibited remarkable biological activities against different microorganisms. The compounds showed suitable drug like properties and are expected to present good bioavailability profile. Discussion: An efficient combination of molecular modeling and biological activity provided an insight into QSAR guide lines that could aid in further development of these derivatives.