Zingiberaceae-derived phytomolecules inhibit Japanese encephalitis virus RNA dependent RNA polymerase: a molecular dynamics study.

The Japanese encephalitis virus, (JEV), is a flavivirus mostly transmitted by Culex mosquitoes mostly present in Southeast Asia and the Western Pacific region. Ardeid-wading birds are the natural reservoir of JEV; nonetheless, pigs are frequently a key amplifying host during epidemics in human populations. Although more domestic animals and wildlife are JEV hosts, it is unclear how these animals fit into the ecology and epidemiology of the virus. Even though there is no specific therapy, vaccines are available to prevent this infection. However, current vaccinations do not work against every clinical isolate and can cause neurological problems in certain people. In this study, we have screened 501 phytochemical compounds from various plants from the Zingeberaceae family against the RdRp protein of JEV. Based on this, the top five compounds (IMPHY014466, IMPHY004928, IMPHY007097, IMPHY014179 and IMPHY005010) were selected based on the obtained docking scores, which was above -8.0 Kcal/mol. Further, the binding affinity of these selected ligands was also analysed using molecular interaction, and the presence of interactions like hydrogen bonds, hydrophobic bonds and polar bonds with respective active residues were identified and studied elaborately. Furthermore, the dynamic stability of the docked RdRp protein with these selected phytochemicals was studied using Molecular dynamic simulation and essential dynamics. The free energy landscape analysis also provided information about the energy transition responsible stability of the complex. The results obtained advocated phytochemical compounds from the zingeberaceae family for future experimental validation, as these compounds exhibited significant potential as JEV antagonists.Communicated by Ramaswamy H. Sarma.

Investigating the effects of four medicinal plants against dengue virus through QSAR modeling and molecular dynamics studies.

The Dengue virus (DENV) has been increasingly recognized as a prevalent viral pathogen responsible for global transmission of infection. It has been established that DENV's NS5 methyltransferase (MTase) controls viral replication. As a result, NS5 MTase is considered a potentially useful drug target for DENV. In this study, the two phases of virtual screening were conducted using the ML-based QSAR model and molecular docking to identify potential compounds against NS5 of DENV. Four medicinal plants [Aloe vera, Cannabis sativa (Hemp), Ocimum sanctum (Holy Basil; Tulsi), and Zingiber officinale (Ginger)] that showed anti-viral properties were selected for sourcing the phytochemicals and screening them against NS5. Additionally, re-docking at higher exhaustiveness and interaction analysis were performed which resulted in the identification of the top four hits (135398658, 5281675, 119394, and 969516) which showed comparable results with the control Sinefungin (SFG). Post molecular dynamics simulation, 135398658 showed the lowest RMSD (0.4-0.5 nm) and the maximum number of hydrogen bonds (eight hydrogen bonds) after the control while 5281675 and 969516 showed comparable hydrogen bonds to the control. These compounds showed direct interactions with the catalytic site residues GLU111 and ASP131, in addition to this these compounds showed stable complex formation as depicted by principal component analysis and free energy landscape. 135398658 showed lower total binding free energy (ΔGTotal = -36.56 kcal/mol) than the control, while 5281675 had comparable values to the control (ΔGTotal = -34.1 kcal/mol). Overall, the purpose of this study was to identify phytochemicals that inhibit NS5 function, that could be further tested experimentally to treat dengue virus (DENV).Communicated by Ramaswamy H. Sarma.

Potential biomarkers in Japanese encephalitis from different hosts and geographical locations.

Japanese encephalitis (JE) is a single-stranded, mosquito-borne, positive-sense RNA flavivirus that causes one of the most severe encephalitides. There are treatments available for those who contact this illness; however, there are no known cures. This disease has a 30% fatality rate, and of the people who survive, 30-50% develops neurologic and psychiatric sequelae. The JE virus genome size is 10.98 kb and contains two coding DNA sequences (CDS), two genes, and 15 mature peptides; the CDS polyprotein is 10.3 kb. In this study, we used 29 genomics sequences of the JE virus reported from different countries and infecting different animals and analysed vast dimensions of the genomic annotation of JE comparatively to understand its evolutionary aspects. The extensive SNPs analysis revealed that KF907505.1, reported from Taiwan, has only three SNPs, similar to sequences reported from India. Repeat and polymorphism analyses revealed that the genome tends to be similar in most JE sequences.

Unveiling the multitargeted potency of Sodium Danshensu against cervical cancer: a multitargeted docking-based, structural fingerprinting and molecular dynamics simulation study.

Cervical Cancer (CC) is one of the most common types of cancer in women worldwide, with a significant number of deaths reported yearly. Despite the various treatment options available, the high mortality rate associated with CC highlights the need to develop new and effective therapeutic agents. In this study, we have screened the complete prepared FDA library against the Mitotic kinesin-like protein 1, Cyclin B1, DNA polymerase, and MCM10-ID using three glide-based molecular docking algorithms: HTVS, SP and XP to produce a robust calculation. All four proteins are crucial proteins that actively participate in CC development, and inhibiting them together can be a game-changer step for multitargeted drug designing. Our multitargeted screening identified Sodium (Na) Danshensu, a natural FDA-approved phenolic compound of caffeic acid derivatives isolated from Salvia miltiorrhiza. The docking score ranges from -5.892 to -13.103 Kcal/mol, and the screening study was evaluated with the pharmacokinetics and interaction fingerprinting to identify the pattern of interactions that revealed that the compound has bound to the best site it can be fitted to where maximum bonds were created to make the complex stable. The molecular dynamics simulations for 100 ns were then extended to validate the stability of the protein-ligand complexes. The results provide insight into the repurposing, and Na-danshensu exhibited strong binding affinity and stable complex formation with the target proteins, indicating its potential as a multitargeted drug against CC.Communicated by Ramaswamy H. Sarma.

Elaeagnus umbellata: A miraculous shrub with potent health-promoting benefits from Northwest Himalaya.

Medicinal plants encompassing a series of bioactive compounds have gained significant importance for use in the treatment of different diseases. Of them, Elaeagnus umbellata Thunb. (Deciduous shrub found in dappled shade, and sunny hedge) exhibits high medicinal value, with a widespread distribution across the Pir Panjal region of the Himalayas. Fruits serve as an excellent source of vitamins, minerals, and other essential compounds that exhibits hypolipidemic, hepatoprotective, and nephroprotective effects. The phytochemical fingerprint of berries revealed them to have a high content of polyphenols (with major proportion of anthocyanins), followed by monoterpenes and vitamin C. Extract of fruits help in regulating the digestion and absorption of glucose and reduces inflammation and oxidative stress. The phytosterols upholding anticoagulant activity serve the purpose of causing decrease in angina and the blood cholesterol levels. Phytochemicals such as eugenol, palmitic acid, and methyl palmitate exhibit potent antibacterial activity against broad range of disease-causing agents. Additionally, a high percentage of essential oils attribute it with the property of being effective against heart ailments. The present study highlights the importance of E. umbellata in traditional medicinal practices, and summarizes the knowledge of its bioactive constituents and a snapshot vision of remarkable biological activities like antimicrobial, antidiabetic, antioxidant, etc towards understanding its role in the development of efficient drug regimens for use in the treatment of different diseases. It also underlines the need to explore the plant on nutritional aspects to strengthen the existing knowledge pertaining to health promoting potential of E. umbellata.

Molecular mechanisms and mode of tamoxifen resistance in breast cancer.

Breast cancer is one of the most common cancers in women around the globe Tamoxifen is used for the last 40 years as an endocrine therapy for breast cancer. This resulted in the reduction of mortality rate by 30% and it still remains one of the most effective therapies against breast cancer. However, resistance against tamoxifen is still one of the major hurdles in the effective management of breast cancer. Intense research has been conducted in the past decade to further explore its resistance mechanism, but still a lot of research will be needed to effectively alleviate this problem. Several biochemical factors and molecular pathways, such as the modulation of ER signaling, upregulation of growth factors had been observed as key factors for tamoxifen resistance (TR). After, initial therapy of five to ten years, breast cancer patients develops resistance towards this drug. The resistance leads to the development of other cancers like uterine cancer. Here, we briefly explore all the molecular events related to tamoxifen resistance and focus on its mechanism of action as well as other pharmacological approaches to better its beneficial effects in the treatment of breast carcinoma.