One of the most significant challenges of diabetes health care is diabetic foot ulcers (DFU). DFUs are more challenging to cure, and this is particularly true for people who already have a compromised immune system. Pathogenic bacteria and fungi are becoming more resistant to antibiotics, so they may be unable to fight microbial infections at the wound site with the antibiotics we have now. This article discusses the dressings, topical antibacterial treatment, medications and debridement techniques used for DFU and provides a deep discussion of DFU and its associated problems. English-language publications on DFU were gathered from many different databases, such as Scopus, Web of Science, Science Direct, Springer Nature, and Google Scholar. For the treatment of DFU, a multidisciplinary approach involving the use of diagnostic equipment, skills, and experience is required. Preventing amputations starts with patient education and the implementation of new categorization systems. The microbiota involved in DFU can be better understood using novel diagnostic techniques, such as the 16S-ribosomal DNA sequence in bacteria. This could be achieved by using new biological and molecular treatments that have been shown to help prevent infections, to control local inflammation, and to improve the healing process.
Objective
The study aimed to synthesize and characterize pyrimidine-linked benzimidazole hybrids, define their antimicrobial and antifungal activities
in vitro
, and determine their ability to inhibit the main protease and spike glycoprotein of SARS-CoV-2.
Methods
The ability of the synthesized compounds to inhibit the main protease and spike glycoprotein inhibitory of SARS-CoV-2 was investigated by assessing their mode of binding to the allosteric site of the enzyme using molecular docking. The structures of pyrimidine-linked benzimidazole derivatives synthesized with microwave assistance were confirmed by spectral analysis. Antibacterial and antifungal activities were determined by broth dilution.
Results
Gram-negative bateria (
Escherichia coli
and
Pseudomonas aeruginosa
) were more sensitive than gram-positive bateria (
Staphylococcus aureus
and
Streptococcus pyogenes
) to the derivatives.
Candida albicans
was sensitive to the derivatives at a minimal inhibitory concentration (MIC) of 250 μg/mL. The novel derivatives had better binding affinity (kcal/mol) than nelfinavir, lopinavir, ivermectin, remdesivir, and favipiravir, which are under investigation as treatment for SARS-CoV-2 infection. Compounds 2c, 2e, and 2g formed four hydrogen bonds with the active cavity of the main protease. Many derivatives had good binding affinity for the RBD of the of SARS-CoV-2 spike glycoprotein with the formation of up to four hydrogen bonds.
Conclusion
We synthesized novel pyrimidine-linked benzi-midazole derivatives that were potent antimicrobial agents with ability to inhibit the SARS-CoV-2 spike glycoprotein. Understanding the pharmacophore features of the main protease and spike glycoprotein offers much scope for the development of more potent agents. We plan to optimize the properties of the derivatives using models
in vivo
and
in vitro
so that they will serve as more effective therapeutic options against bacterial and SARS-CoV-2 infections.
Background:
COVID-19 (SARS-CoV-2 infection) has affected almost every region of the world. Presently, there is no defined line of treatment available for it. Triphala is already proven to have a safe biological window and well known for its antioxidant and immunomodulatory properties.
Objective:
Present work has been carried out to study Triphala's effectiveness for the treatment of COVID-19.
Methods:
The Receptor-binding domain (RBD) of SARS-CoV-2 Spike Glycoprotein responsible for the invasion into the host cell, which leads to further infection. The molecular docking (MD) was performed to explore the binding affinities (kcal/mol) of Triphala's chemical constituents and compared them with the existing drugs under investigation for the treatment of COVID-19 epidemiology.
Results:
Chebulinic acid binding affinity -8.5 kcal/mol with the formation of 10 hydrogen bonds. Almost all the major chemical constituents have formed two or more hydrogen bonds with RBD of SARS-CoV-2 Spike Glycoprotein.
Conclusion:
The present study showed that Triphala might perform vital roles in the treatment of COVID-19 and expand its usefulness to physicians to treat this illness. There is a need to complete the in-vitro, in-vivo biological testing of Triphala on SARS-CoV-2 disease to create more quality data. The binding mode of Chebulinic acid in the allosteric cavity allows a better understanding of RBD of SARS-CoV-2 Spike Glycoprotein target and provides insight for the design of new inhibitors. Triphala is already proven to have a safe biological window, which indicates we can skip the pre-clinical trials. Apart from this, Triphala is well known for its antioxidant properties, which ultimately improves the immunity of the COVID-19 patient.
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