The re-emerging Zika virus (ZIKV) is an arthropod-borne virus that has been described to have explosive potential as a worldwide pandemic. The initial transmission of the virus was through a mosquito vector, however, evolving modes of transmission has allowed the spread of the disease over continents. The virus has already been linked to irreversible chronic central nervous system conditions. The concerns of the scientific and clinical community are the consequences of Zika viral mutations, thus suggesting the urgent need for viral inhibitors. There have been large strides in vaccine development against the virus but there are still no FDA approved drugs available. Rapid rational drug design and discovery research is fundamental in the production of potent inhibitors against the virus that will not just mask the virus, but destroy it completely. In silico drug design allows for this prompt screening of potential leads, thus decreasing the consumption of precious time and resources. This study demonstrates an optimized and proven screening technique in the discovery of two potential small molecule inhibitors of ZIKV Methyltransferase and RNA dependent RNA polymerase. This in silico ‘per-residue energy decomposition pharmacophore’ virtual screening approach will be critical in aiding scientists in the discovery of not only effective inhibitors of Zika viral targets, but also a wide range of anti-viral agents.

Aim: Amid the current global challenge of antimicrobial resistance, RNA polymerase remains a paramount therapeutic target for tuberculosis. Dual binding of rifampin (RIF) and a novel compound, DAAP1, demonstrated the suppression of RIF resistance. However, a paucity of data elucidating the structural mechanism of action of this synergistic interaction prevails. Methodology & results: Molecular dynamic simulations unraveled the synergistic inhibitory characteristics of DAAP1 and RIF. Co-binding induced a stable protein, increased the degree of compactness of binding site residues around RIF and subsequently an improved binding affinity toward RIF. Conclusion: Findings established the structural mechanism by which DAAP1 stabilizes Mycobacterium tuberculosis RNA polymerase, thus possibly suppressing RIF resistance. This study will assist toward the design of novel inhibitors combating drug resistance in tuberculosis.

The Zika virus has emerged as a pathogen of major health concern. The rapid spread of the virus has led to uproar in the medical domain as scientists frantically race to develop effective vaccines and small molecules to inhibit the virus. In the past year, there has been a flood of Zika knowledge published including its characteristics, transmission routes and its role in disease conditions such as microcephaly and Gullian–Barŕe syndrome. Targeted therapy against specific viral maturation proteins is necessary in halting the replication of the virus in the human host, thus decreasing host–host transmission. This prompted us to investigate the structural properties of the Zika NS3 helicase when bound to ATP-competitive inhibitor, NITD008. In this study, comparative molecular dynamic simulations were employed for APO and bound protein to demonstrate the molecular mechanism of the helicase. Results clearly revealed that NITD008-binding caused significant residue fluctuations at the P-loop compared to the rigid nature of the APO conformation. The NITD008-helicase complex also revealed residues 339–348 to transition from a ₃10-helix to a stable α-helix. These protein fluctuations were verified by investigation of dynamic cross correlation and principal component analysis. The fundamental dynamic analysis presented in this report is crucial in understanding Zika NS3 helicase function, thereby giving insights toward an inhibition mechanism. The information reported on the binding mode at the ATPase active site may also assist in designing effective inhibitors against this detrimental viral target.

Recent scientific trends have revealed that the collection and analysis of data on the occurrence and fate of SARS-CoV-2 in wastewater may serve as an early warning system for COVID-19. In South Africa, the first COVID-19 epicenter emerged in the Western Cape Province. The City of Cape Town, located in the Western Cape Province, has approximately 4 million inhabitants. This study reports on the monitoring of SARS-CoV-2 RNA in the wastewater of the City of Cape Town’s wastewater treatment plants (WWTPs) during the peak of the epidemic. During this period, the highest overall median viral RNA signal was observed in week 1 (9200 RNA copies/mL) and declined to 127 copies/mL in week 6. The overall decrease in the amount of detected viral SARS-CoV-2 RNA over the 6-week study period was associated with a declining number of newly identified COVID-19 cases in the city. The SARS-CoV-2 early warning system has now been established to detect future waves of COVID-19.

Structural mechanism of inhibition of NAZ2329 at the allosteric site of PTPRZ, with particular emphasis on the dynamics of the WPD-loop.