Investigating forthcoming strategies to tackle deadly superbugs: current status and future vision.

INTRODUCTION: Superbugs are microorganisms that cause disease and have increased resistance to the treatments typically used against infections. Recently, antibiotic resistance development has been more rapid than the pace at which antibiotics are manufactured, leading to refractory infections. Scientists are concerned that a particularly virulent and lethal 'superbug' will one day join the ranks of existing bacteria that cause incurable diseases, resulting in a global health disaster on the scale of the Black Death. AREAS COVERED: This study highlights the current developments in the management of antibiotic-resistant bacteria and recommends strategies for further regulating antibiotic-resistant microorganisms associated with the healthcare system. This review also addresses the origins, prevalence, and pathogenicity of superbugs, and the design of antibacterial against these growing multidrug-resistant organisms from a medical perspective. EXPERT OPINION: It is recommended that antimicrobial resistance should be addressed by limiting human-to-human transmission of resistant strains, lowering the use of broad-spectrum antibiotics, and developing novel antimicrobials. Using the risk-factor domains framework from this study would assure that not only clinical but also community and hospital-specific factors are covered, lowering the chance of confounders. Extensive subjective research is necessary to fully understand the underlying factors and uncover previously unexplored areas.

Toward the Identification of Natural Antiviral Drug Candidates against Merkel Cell Polyomavirus: Computational Drug Design Approaches.

Merkel cell carcinoma (MCC) is a rare form of aggressive skin cancer mainly caused by Merkel cell polyomavirus (MCPyV). Most MCC tumors express MCPyV large T (LT) antigens and play an important role in the growth-promoting activities of oncoproteins. Truncated LT promotes tumorigenicity as well as host cell proliferation by activating the viral replication machinery, and inhibition of this protein in humans drastically lowers cellular growth linked to the corresponding cancer. Our study was designed with the aim of identifying small molecular-like natural antiviral candidates that are able to inhibit the proliferation of malignant tumors, especially those that are aggressive, by blocking the activity of viral LT protein. To identify potential compounds against the target protein, a computational drug design including molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized Born surface area (MM-GBSA) approaches were applied in this study. Initially, a total of 2190 phytochemicals isolated from 104 medicinal plants were screened using the molecular docking simulation method, resulting in the identification of the top five compounds having the highest binding energy, ranging between -6.5 and -7.6 kcal/mol. The effectiveness and safety of the selected compounds were evaluated based on ADME and toxicity features. A 250 ns MD simulation confirmed the stability of the selected compounds bind to the active site (AS) of the target protein. Additionally, MM-GBSA analysis was used to determine the high values of binding free energy (ΔG bind) of the compounds binding to the target protein. The five compounds identified by computational approaches, Paulownin (CID: 3084131), Actaealactone (CID: 11537736), Epigallocatechin 3-O-cinnamate (CID: 21629801), Cirsilineol (CID: 162464), and Lycoricidine (CID: 73065), can be used in therapy as lead compounds to combat MCPyV-related cancer. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the virus.

Therapeutic potential of indole alkaloids in respiratory diseases: A comprehensive review.

BACKGROUND: Indole alkaloids are very promising for potential therapeutic purposes and appear to be particularly effective against respiratory diseases. Several experimental studies have been performed, both in vivo and in vitro, to evaluate the effectiveness of indole alkaloids for the management of respiratory disorders, including asthma, emphysema, tuberculosis, cancer, and pulmonary fibrosis. PURPOSE: The fundamental objective of this review was to summarize the in-depth therapeutic potential of indole alkaloids against various respiratory disorders. STUDY DESIGN: In addition to describing the therapeutic potential, this review also evaluates the toxicity of these alkaloids, which have been utilized for therapeutic benefits but have demonstrated toxic consequences. Some indole alkaloids, including scholaricine, 19-epischolaricine, vallesamine, and picrinine, which are derived from the plant Alstonia scholaris, have shown toxic effects in non-rodent models. METHODS: This review also discusses clinical studies exploring the therapeutic efficacy of indole alkaloids, which have confirmed the promising benefits observed in vivo and in vitro. RESULTS: The indole alkaloidal compounds have shown efficacy in subjects with respiratory diseases. CONCLUSION: The available data established both preclinical and clinical studies confirm the potential of indole alkaloids to treat the respiratory disorders.