Cheminformatics bioprospection of selected medicinal plants metabolites against trypsin cleaved VP4 (spike protein) of rotavirus A.

Rotaviruses have continued to be the primary cause of acute dehydrating diarrhoea in children under five years of age despite the global introduction of four World Health Organization (WHO) prequalified oral vaccines in over 106 countries. Currently, no medication is approved by the Food and Drug Administration (FDA) specifically for treating rotavirus A-induced diarrhoea. Consequently, it is important to focus on developing prophylactic and curative therapeutics to combat rotaviral infections. For the first time, this study computationally screened and identified metabolites from Spondias mombin, Macaranga barteri and Dicerocaryum eriocarpum as potential novel inhibitors with broad-spectrum activity against VP5* and VP8* (spike protein) of rotavirus A (RVA). The initial top 20 metabolites identified through molecular docking were further filtered using drug-likeness and pharmacokinetics parameters. The molecular properties of the resulting top-ranked compounds were predicted by conducting density functional theory (DFT) calculations, while molecular dynamics (MD) simulation revealed their thermodynamic compatibility with a significant affinity towards VP8* than VP5*. Except for ellagic acid (-11.78 kcal/mol), the lead compounds had higher binding free energy than the reference standard (VP5* (-11.81 kcal/mol), VP8* (-14.12 kcal/mol)) with 2SG (-20.98 kcal/mol) and apigenin-4'-glucoside (-23.56 kcal/mol) having the highest affinity towards VP5* and VP8*, respectively. Of all the top-ranked compounds, better broad-spectrum affinities for both VP5* and VP8* than tizoxanide were observed in 2SG (VP5* (-20.98 kcal/mol), VP8* (-20.13 kcal/mol)) and sericetin (VP5* (-20.46 kcal/mol), VP8* (-18.31 kcal/mol)). While the identified leads could be regarded as potential modulators of the investigated therapeutic targets for effective management of rotaviral infection, additional in vitro and in vivo evaluation is strongly recommended, and efforts are on-going in this regard.Communicated by Ramaswamy H. Sarma.

Metabolites profiling and cheminformatics bioprospection of selected medicinal plants against the main protease and RNA-dependent RNA polymerase of SARS-CoV-2.

Despite the existence of some vaccines, SARS-CoV-2 (S-2) infections persist for various reasons relating to vaccine reluctance, rapid mutation rate, and an absence of specific treatments targeted to the infection. Due to their availability, low cost and low toxicity, research into potentially repurposing phytometabolites as therapeutic alternatives has gained attention. Therefore, this study explored the antiviral potential of metabolites of some medicinal plants [Spondias mombin, Macaranga barteri and Dicerocaryum eriocarpum (Sesame plant)] identified using liquid chromatography-mass spectrometry (LCMS) as possible inhibitory agents against the S-2 main protease (S-2 MP) and RNA-dependent RNA polymerase (RP) using computational approaches. Molecular docking was used to identify the compounds with the best affinities for the selected therapeutics targets. Afterwards, compounds with poor physicochemical characteristics, pharmacokinetics, and drug-likeness were screened out. The top-ranked compounds were further subjected to a 120-ns molecular dynamics (MD) simulation. Only quercetin 3-O-rhamnoside (-48.77 kcal/mol) had higher binding free energy than the reference standard (zafirlukast) (-44.99 kcal/mol) against S-2 MP. Conversely, all the top-ranked compounds (ellagic acid hexoside, spiraeoside, apigenin-4'-glucoside and chrysoeriol 7-glucuronide) except gnetin L (-24.24 kcal/mol) had higher binding free energy (-55.19 kcal/mol, -52.75 kcal/mol, -47.22 kcal/mol and -43.35 kcal/mol) respectively, against S-2 RP relative to the reference standard (-34.79 kcal/mol). The MD simulations study further revealed that the investigated inhibitors are thermodynamically stable and form structurally compatible complexes that impede the regular operation of the respective S-2 therapeutic targets. Although, these S-2 therapeutic candidates are promising, further in vitro and in vivo evaluation is required and highly recommended.Communicated by Ramaswamy H. Sarma.

Waste to Medicine: Evidence from Computational Studies on the Modulatory Role of Corn Silk on the Therapeutic Targets Implicated in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and/or defective insulin production in the human body. Although the antidiabetic action of corn silk (CS) is well-established, the understanding of the mechanism of action (MoA) behind this potential is lacking. Hence, this study aimed to elucidate the MoA in different samples (raw and three extracts: aqueous, hydro-ethanolic, and ethanolic) as a therapeutic agent for the management of T2DM using metabolomic profiling and computational techniques. Ultra-performance liquid chromatography-mass spectrometry (UP-LCMS), in silico techniques, and density functional theory were used for compound identification and to predict the MoA. A total of 110 out of the 128 identified secondary metabolites passed the Lipinski's rule of five. The Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis revealed the cAMP pathway as the hub signaling pathway, in which ADORA1, HCAR2, and GABBR1 were identified as the key target genes implicated in the pathway. Since gallicynoic acid (-48.74 kcal/mol), dodecanedioc acid (-34.53 kcal/mol), and tetradecanedioc acid (-36.80 kcal/mol) interacted well with ADORA1, HCAR2, and GABBR1, respectively, and are thermodynamically stable in their formed compatible complexes, according to the post-molecular dynamics simulation results, they are suggested as potential drug candidates for T2DM therapy via the maintenance of normal glucose homeostasis and pancreatic ß-cell function.

A review on disinfection methods for inactivation of waterborne viruses.

Water contamination is a global health problem, and the need for safe water is ever-growing due to the public health implications of unsafe water. Contaminated water could contain pathogenic bacteria, protozoa, and viruses that are implicated in several debilitating human diseases. The prevalence and survival of waterborne viruses differ from bacteria and other waterborne microorganisms. In addition, viruses are responsible for more severe waterborne diseases such as gastroenteritis, myocarditis, and encephalitis among others, hence the need for dedicated attention to viral inactivation. Disinfection is vital to water treatment because it removes pathogens, including viruses. The commonly used methods and techniques of disinfection for viral inactivation in water comprise physical disinfection such as membrane filtration, ultraviolet (UV) irradiation, and conventional chemical processes such as chlorine, monochloramine, chlorine dioxide, and ozone among others. However, the production of disinfection by-products (DBPs) that accompanies chemical methods of disinfection is an issue of great concern due to the increase in the risks of harm to humans, for example, the development of cancer of the bladder and adverse reproductive outcomes. Therefore, this review examines the conventional disinfection approaches alongside emerging disinfection technologies, such as photocatalytic disinfection, cavitation, and electrochemical disinfection. Moreover, the merits, limitations, and log reduction values (LRVs) of the different disinfection methods discussed were compared concerning virus removal efficiency. Future research needs to merge single disinfection techniques into one to achieve improved viral disinfection, and the development of medicinal plant-based materials as disinfectants due to their antimicrobial and safety benefits to avoid toxicity is also highlighted.

Global public health implications of human exposure to viral contaminated water.

Enteric viruses are common waterborne pathogens found in environmental water bodies contaminated with either raw or partially treated sewage discharge. Examples of these viruses include adenovirus, rotavirus, noroviruses, and other caliciviruses and enteroviruses like coxsackievirus and polioviruses. They have been linked with gastroenteritis, while some enteric viruses have also been implicated in more severe infections such as encephalitis, meningitis, hepatitis (hepatitis A and E viruses), cancer (polyomavirus), and myocarditis (enteroviruses). Therefore, this review presents information on the occurrence of enteric viruses of public health importance, diseases associated with human exposure to enteric viruses, assessment of their presence in contaminated water, and their removal in water and wastewater sources. In order to prevent illnesses associated with human exposure to viral contaminated water, we suggest the regular viral monitoring of treated wastewater before discharging it into the environment. Furthermore, we highlight the need for more research to focus on the development of more holistic disinfection methods that will inactivate waterborne viruses in municipal wastewater discharges, as this is highly needed to curtail the public health effects of human exposure to contaminated water. Moreover, such a method must be devoid of disinfection by-products that have mutagenic and carcinogenic potential.