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.

Ebola still remains as one of the most problematic infectious diseases in Africa with a high rate of mortality. Although this disease has been known for an almost half-century, there are no vaccines and drugs available in the market to treat Ebola. Zaire ebolavirus (EBOV), a single-stranded RNA virus which belongs to Filoviridae family and Mononegavirales order, is one of the virus causing Ebola. As one of seven proteins that EBOV encodes, Ebola virus nucleoprotein (EBOV NP) plays an imperative role in EBOV proliferation cycle. Therefore, the development of a new Ebola treatment can be targeted towards EBOV NP. In this work, we screened about 190,084 natural product compounds from ZINC15 database through in silico virtual screening and flexible docking simulation. Furthermore, the bioavailability and toxicity prediction have been conducted as well. Two best ligands according to the simulation and prediction tests were progressed into the molecular dynamics simulation. In the end, we found that our proposed ligands, namely α-lipomycin (ZINC56874155) and 3-(((S)-1-amino-1,2,3,4-tetrahydroisoquinolin-5-yl)methyl)-5-((5-((5R,7S)-5,7-dihydroxy-3-oxodecyl)-2-hydroxyphenoxy) methyl)pyrrolo[3,4-b]pyrrol-5-ium (ZINC85628951), showed the promising results to be developed as a lead compounds for treating Ebola. Therefore, an experimental study is required to validate their inhibition activities against EBOV NP.

Peptides are preferred for designing inhibitors because of their high activity and specificity. Seven cyclopentapeptide inhibitors were designed in this study against dengue virus type 2 (DEN-2) NS3-NS2B protease: CKRRC, CGRRC, CRGRC, CRTRC, CTRRC, CKRKC and CRRKC. Docking analysis was performed to study the enzyme-inhibitor binding interactions. The free energy binding and estimated Ki values for all the inhibitors were found to be small (within micromolar range), indicating that the inhibitors bind considerably well to the binding site. The results showed that the cyclopentapeptide CKRKC was the best peptide inhibitor candidate with estimated free binding energy of -8.39 kcal/mol and Ki of 0.707 ?M when compared to the standard inhibitor Bz-Nle-Lys-Arg-Arg-H that has been experimentally tested and shown to exhibit Ki value of 5.8 ?M. Several modes of weak interactions were observed between the cyclopentapeptide CKRKC and the active site of DEN-2 NS3-NS2B protease. Thus, the cyclopentapeptide is proposed as a potential inhibitor to the NS3-NS2B protease activities of DEN-2. While these preliminary results are promising, further experimental investigation is necessary to validate the results.

Meningitis infection is one of the major threats during Hajj season in Mecca. Meningitis vaccines are available, but their uses are limited in some countries du...