Control of Mycobacterium tuberculosis infection continues to be an issue, particularly in countries with a high tuberculosis (TB) burden in the tropical and sub-tropical regions. The effort to reduce the catastrophic cost of TB with the WHO’s End TB Strategy in 2035 is still obstructed by the emergence of drug-resistant TB (DR-TB) cases as result of various mutations of the MTB strain. In the approach to combat DR-TB, several potential antitubercular agents were discovered as inhibitors for various existing and novel targets. Host-directed therapy and immunotherapy also gained attention as the drug-susceptibility level of the pathogen can be reduced due to the pathogen’s evolutionary dynamics. This review is focused on the current progress and challenges in DR-TB treatment. We briefly summarized antitubercular compounds that are under development and trials for both DR-TB drug candidates and host-directed therapy. We also highlighted several problems in DR-TB diagnosis, the treatment regimen, and drug discovery that have an impact on treatment adherence and treatment failure.

Epimutation by DNA Methyltransferase 1 (DNMT1), an epigenetic regulator enzyme, may lead to the proliferation of breast cancer. In this report, 168,686 natural products from the PubChem database were screened and modified by in silico method to acquire the potential inhibitor of DNMT1. The initial screening of PubChem natural products using Lipinski’s and Veber’s rules of three and toxic properties have resulted in 2601 fragment candidates. Four fragments from pharmacophore-based molecular docking simulation were modified by utilizing FragFP and the Lipinski’s and Veber’s rules of five, and resulted in 51,200 ligands. The toxicological screening collected 13,563 ligands for a series of pharmacophore-based molecular docking simulations to sort out the modified ligands, which had the better binding activity and interactions to DNMT1 compared to the standards, SAH, SAM, and SFG. This step resulted in five ligand candidates, namely C-7756, C-5769, C-1723, C-2129, and C-2140. The ADME-Tox properties prediction showed that the selected ligands are generally better than standards in terms of druglikeness, GI absorption, and oral bioavailability. C-7756 exhibited a stronger affinity to DNMT1 as well as better ADME-Tox properties compared to the other ligands.

Dengue Fever (DF) has emerged as a significant public health problem of international concern with its high prevalence in the tropic and subtropical regions. Dengue Virus (DENV), which is the cause of DF, consists of four serotypes of antigenically distinct viruses. The immense variation and limited identity similarity at the amino acid level lead to a problematic challenge in the development of an efficacious vaccine. Fortunately, the extensively available immunological data, the advance in antigenic peptide prediction, and the incorporation of molecular docking and dynamics simulation in immunoinformatics have directed the vaccine development towards the rational design of the epitope-based vaccine. Here, we point out the current state of dengue epidemiology and the recent development in vaccine development. Subsequently, we provide a systematic review of our validated method and tools for B- and T-cell epitope prediction as well as the use of molecular docking and dynamics in evaluating epitope affinity and stability in the discovery of a new tetravalent dengue vaccine through computational epitope-based vaccine design.

Ebola virus (EBOV) is a negative-sense RNA virus that belongs to Filoviridae family which recognized as one of the deadliest virus that can cause severe haemorrhagic fever. Recent studies have shown that heat-shock protein 90 (Hsp90), an essential molecular chaperone, plays an imperative role in the replication of EBOV. In the present study, about 112,113 biogenic compounds from ZINC15 database were screened through computational study through Rule of Three, druglikeness, and toxicity screening, followed by molecular docking simulation to determine the potential biogenic-based compound as lead compounds. These compounds were later linked by each other to generate a novel compound for inhibiting Hsp90 protein. Throughout this study, about 742 fragments were obtained through the first screening process, while the first docking simulation produced 452 lead fragments. After the linking processes were conducted, about 81 compounds were produced through the second docking simulation. Furthermore, the docking simulation also revealed that HAI_77 gave the best ligand interaction and had the lowest Gibbs free binding energy at -14.157 kcal/mol. Thus, HAI_77 ligand can be proposed as novel drug candidates for the EBOV therapeutics targeting Hsp90 ligand.

Coumarins are compounds that are naturally found in various plants and are known for their potential pharmacological characteristics, such as anti-inflammatory, antibacterial, antiparasitic, and anticoagulant activities. Despite the potential pharmacological properties, structural modification of coumarins is important to enhance the biological activity, solubility, bioavailability, and various therapeutic characteristics. Microbial transformation is a promising method to modify coumarins since this method offers regioselective and stereospecific transformation, which is challenging to obtain through chemical synthesis. Various microorganisms, including bacteria and fungi, play an essential role in the microbial transformation of coumarins. These microorganisms employ enzymatic mechanisms involving various enzymes to catalyze several reactions, such as hydroxylation, oxidation, reduction, and demethylation. Among these microbial transformation processes, the demethylation process is a significant mechanism for altering the bioactivity of coumarins by converting methoxy groups into hydroxyl groups. Despite all the advantages, microbial transformation also has limitations such as low substrate specificity, contamination during inoculation, variable enzymatic activity, and challenges to scale up the production of bioactive coumarins. These challenges can be addressed through the optimization of the bioprocess to enhance the efficiency of microbial coumarin metabolism. This review provides a comprehensive overview of the microbial transformation of coumarins, highlighting the role of various microorganisms, enzymatic mechanisms, and the transformation processes.