A Multifaceted Computational Approach to Understanding the MERS-CoV Main Protease and Brown Algae Compounds' Interaction.

Middle East Respiratory Syndrome (MERS) is a viral respiratory disease caused b a special type of coronavirus called MERS-CoV. In the search for effective substances against the MERS-CoV main protease, we looked into compounds from brown algae, known for their medicinal benefits. From a set of 1212 such compounds, our computer-based screening highlighted four-CMNPD27819, CMNPD1843, CMNPD4184, and CMNPD3156. These showed good potential in how they might attach to the MERS-CoV protease, comparable to a known inhibitor. We confirmed these results with multiple computer tests. Studies on the dynamics and steadiness of these compounds with the MERS-CoV protease were performed using molecular dynamics (MD) simulations. Metrics like RMSD and RMSF showed their stability. We also studied how these compounds and the protease interact in detail. An analysis technique, PCA, showed changes in atomic positions over time. Overall, our computer studies suggest brown algae compounds could be valuable in fighting MERS. However, experimental validation is needed to prove their real-world effectiveness.

Exploration of Microbially Derived Natural Compounds against Monkeypox Virus as Viral Core Cysteine Proteinase Inhibitors.

Monkeypox virus (MPXV) is a member of the Orthopoxvirus genus and the Poxviridae family, which instigated a rising epidemic called monkeypox disease. Proteinases are majorly engaged in viral propagation by catalyzing the cleavage of precursor polyproteins. Therefore, proteinase is essential for monkeypox and a critical drug target. In this study, high-throughput virtual screening (HTVS) and molecular dynamics simulation were applied to detect the potential natural compounds against the proteinase of the monkeypox virus. Here, 32,552 natural products were screened, and the top five compounds were selected after implementing the HTVS and molecular docking protocols in series. Gallicynoic Acid F showed the minimum binding score of -10.56 kcal/mole in the extra precision scoring method, which reflected the highest binding with the protein. The top five compounds showed binding scores ≤-8.98 kcal/mole. These compound complexes were tested under 100 ns molecular dynamics simulation, and Vaccinol M showed the most stable and consistent RMSD trend in the range of 2 Å to 3 Å. Later, MM/GBSA binding free energy and principal component analysis were performed on the top five compounds to validate the stability of selected compound complexes. Moreover, the ligands Gallicynoic Acid F and H2-Erythro-Neopterin showed the lowest binding free energies of -61.42 kcal/mol and -61.09 kcal/mol, respectively. Compared to the native ligand TTP-6171 (ΔGBind = -53.86 kcal/mol), these two compounds showed preferable binding free energy, suggesting inhibitory application against MPXV proteinase. This study proposed natural molecules as a therapeutic solution to control monkeypox disease.

Prevalence of permethrin-resistant kdr mutation in head lice (Pediculus humanus capitis) from elementary school students in Jeddah, Saudi Arabia.

Head lice (Pediculus humanus capitis) are a major global concern, and there is growing evidence of an increase in head lice prevalence among Saudi schoolchildren. The purpose of this study is to investigate the prevalence of an insecticidal resistance mutation in head lice collected from schoolchildren. A polymerase chain reaction (PCR) was used to amplify a segment of the voltage-gated sodium channel gene subunit to assess the prevalence and distribution of the kdr T917I mutation in head lice. Subsequently, the restriction fragment length polymorphism (RFLP) patterns revealed two genotypic forms: homozygous-susceptible (SS) and homozygous-resistant (RR). The results showed that 17 (37.80%) of the 45 samples were SS, whereas 28 (62.2%) were RR and T917I and L920F point mutations were found in the nucleotide and amino acid sequences of RR. Compared to other nations, the frequency of permethrin resistance mutation in the head louse population in Saudi Arabia was low. This study provides the first evidence of permethrin resistance mutation in human head lice in Saudi Arabia. The findings of this study will highlight the rising incidence of the kdr mutation in head lice in Saudi Arabia.

Cheminformatics Strategies Unlock Marburg Virus VP35 Inhibitors from Natural Compound Library.

The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae and are highly hazardous and contagious viruses. With a mortality rate ranging from 23% to 90%, depending on the specific outbreak, the development of effective antiviral interventions is crucial for reducing fatalities and mitigating the impact of Marburg virus outbreaks. In this investigation, a virtual screening approach was employed to evaluate 2042 natural compounds for their potential interactions with the VP35 protein of the Marburg virus. Average and worst binding energies were calculated for all 20 poses, and compounds that exhibited binding energies <-6 kcal/mol in both criteria were selected for further analysis. Based on binding energies, only six compounds (Estradiol benzoate, INVEGA (paliperidone), Isosilybin, Protopanaxadiol, Permethrin, and Bufalin) were selected for subsequent investigations, focusing on interaction analysis. Among these selected compounds, Estradiol benzoate, INVEGA (paliperidone), and Isosilybin showed strong hydrogen bonds, while the others did not. In this study, the compounds Myricetin, Isosilybin, and Estradiol benzoate were subjected to a molecular dynamics (MD) simulation and free binding energy calculation using MM/GBSA analysis. The reference component Myricetin served as a control. Estradiol benzoate exhibited the most stable and consistent root-mean-square deviation (RMSD) values, whereas Isosilybin showed significant fluctuations in RMSD. The compound Estradiol benzoate exhibited the lowest ΔG binding free energy (-22.89 kcal/mol), surpassing the control compound's binding energy (-9.29 kcal/mol). Overall, this investigation suggested that Estradiol benzoate possesses favorable binding free energies, indicating a potential inhibitory mechanism against the VP35 protein of the Marburg virus. The study proposes that these natural compounds could serve as a therapeutic option for preventing Marburg virus infection. However, experimental validation is required to further corroborate these findings.

Investigating the Mechanism of Action of Anti-Dengue Compounds as Potential Binders of Zika Virus RNA-Dependent RNA Polymerase.

The World Health Organization (WHO) has designated the Zika virus (ZIKV) as a significant risk to the general public's health. Currently, there are no vaccinations or medications available to treat or prevent infection with the Zika virus. Thus, it is urgently required to develop a highly efficient therapeutic molecule. In the presented study, a computationally intensive search was carried out to identify potent compounds that have the potential to bind and block the activity of ZIKV NS5 RNA-dependent RNA polymerase (RdRp). The anti-dengue chemical library was subjected to high-throughput virtual screening and MM/GBSA analysis in order to rate the potential candidates. The top three compounds were then chosen. According to the MM/GBSA analysis, compound 127042987 from the database had the highest binding affinity to the protein with a minimum binding free energy of -77.16 kcal/mole. Compound 127042987 had the most stable RMSD trend and the greatest number of hydrogen bond interactions when these chemical complexes were evaluated further under a 100 ns molecular dynamics simulation. Compound 127042987 displayed the best binding free energy (GBind) of -96.50 kcal/mol, surpassing the native ligand binding energy (-66.17 kcal/mole). Thereafter, an MM/GBSA binding free energy study was conducted to validate the stability of selected chemical complexes. Overall, this study illustrated that compound 127042987 showed preferred binding free energies, suggesting a possible inhibitory mechanism against ZIKV-RdRp. As per this study, it was proposed that compound 127042987 could be used as a therapeutic option to prevent Zika virus infection. These compounds need to be tested in experiments for further validation.