The Semliki Forest Virus (SFV) is an RNA virus with a positive-strand that belongs to the Togaviridae family’s Alphavirus genus. An epidemic was observed among French troops stationed in the Central African Republic, most likely caused by the SFV virus. The two transmembrane proteins El and E2 and the peripheral protein E3 make up the viral spike protein. The virus binds to the host cell and is internalized via endocytosis; endosome acidification causes the E1/E2 heterodimer to dissociate and the E1 subunits to trimerize. Lupenone was evaluated against the E1 spike protein of SFV in this study based on state-of-the-art cheminformatics approaches, including molecular docking, molecular dynamics simulation, and binding free energy calculation. The molecular docking study envisaged major interactions of Lupenone with binding cavity residues involved non-bonded van der Waal’s and Pi-alkyl interactions. Molecular dynamic simulation of a time scale 200 ns corroborated interaction pattern with molecular docking studies between Lupenone and E1 spike protein. Nevertheless, Lupenone intearcation with the E1 spike protein conforming into a stable complex substantiated by free energy landscape (FEL), PCA analysis. Free energy decomposition of the binding cavity resdiues of E1 spike protein also ensured the efficient non-bonded van der Waal’s interaction contributing most energy to interact with the Lupenone. Therefore, Lupenone interacted strongly at the active site conforming into higher structural stability throughout the dynamic evolution of the complex. Thus, this study perhaps comprehend the efficiency of Lupenone as lead molecule against SFV E1 spike protein for future therapeutic purpose.

Heat shock protein 27 (HSP27) is a protein that works as a chaperone and an antioxidant and is activated by heat shock, environmental stress, and pathophysiological stress. However, HSP27 dysregulation is a characteristic of many human cancers. HSP27 suppresses apoptosis and cytoskeletal reorganization. As a result, it is recognized as a critical therapeutic target for effective cancer therapy. Despite the effectiveness of multiple HSP27 inhibitors in pre-clinical investigations and clinical trials, no HSP27 inhibitor has progressed to the anticancer phase of the development. These difficulties have mostly been attributable to existing anticancer therapies’ inability to target oncogenic HSP27. Highly selective HSP27 inhibitors with higher effective-ness and low toxicity led to the development of combination techniques that include computer-aided assisted therapeutic discovery and design. This study emphasizes the most recent results and roles of HSP27 in cancer and the potential for utilizing an anticancer chemical database to uncover novel compounds to inhibit HSP27.

Exosome‐based targeted delivery of Proteolysis‐Targeting Chimeras (PROTACs) is an innovative approach that provides a promising solution for addressing the complex issues of viral diseases. This strategy significantly mitigates the off‐target effects associated with traditional therapeutics by facilitating targeted delivery of PROTACs, which in turn enhances the overall therapeutic outcomes. Challenges like poor pharmacokinetics and unintended side effects, commonly observed with conventional PROTACs usage, are effectively managed with this approach. Emerging evidence affirms the potential of this delivery mechanism in curbing viral replication. However, it is crucial to undertake more comprehensive investigations for optimizing exosome‐based delivery systems and conducting stringent safety and efficacy assessments within preclinical and clinical settings. The advancements in this field could potentially redefine the therapeutic landscape for viral diseases, opening new vistas for their management and treatment.

COVID-19 has become one of the few leading causes of death and has evolved into a pandemic that disrupts everyone’s routine, and balanced way of life worldwide, and will continue to do so. To bring an end to this pandemic, scientists had put their all effort into discovering the vaccine for SARS-CoV-2 infection. For their dedication, now, we have a handful of COVID-19 vaccines. Worldwide, millions of people are at risk due to the current pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite the lack of clinically authorized antiviral medications and vaccines for COVID-19, clinical trials of many recognized antiviral agents, their combination, and vaccine development in patients with confirmed COVID-19 are still ongoing. This discovery gave us a chance to get immune to this disease worldwide and end the pandemic. However, the unexpected capacity of mutation of the SARS-CoV-2 virus makes it difficult, like the recent SAS-CoV-2 Omicron variant. Therefore, there is a great necessity to spread the vaccination programs and prevent the spread of this dreadful epidemic by identifying and isolating afflicted patients. Furthermore, several COVID-19 tests are thought to be expensive, time-consuming, and require the use of adequately qualified persons to be carried out efficiently. In addition, we also conversed about how the various COVID-19 testing methods can be implemented for the first time in a developing country and their cost-effectiveness, accuracy, human resources requirements, and laboratory facilities. Graphical abstract

A high incidence of dementia (60–80%) and a high rate of memory loss are two of the most common symptoms of Alzheimer’s disease (AD), which affects the elderly. Researchers have recommended that traditional Chinese medicine (TCM) and Indian medicines can be used to prevent and cure AD. Several studies have linked neuroinflammation linked to amyloid-β (Aβ) deposition in the brain to the pathophysiology of neurodegenerative disorders. As a result, more research is needed to determine the role of inflammation in neurodegeneration. Increased microglial activation, cytokine production, reactive oxygen species (ROS), and nuclear factor kappa B (NF-κB) all play a role in the inflammatory process of AD. This review focuses on the role of neuroinflammation in neuroprotection and the molecular processes used by diverse natural substances, phytochemicals, and herbal formulations in distinct signaling pathways. Currently, researchers are focusing on pharmacologically active natural compounds with the anti-neuroinflammatory potential, making them a possible contender for treating AD. Furthermore, the researchers investigated the limits of past studies on TCM, Indian Ayurveda, and AD. Numerous studies have been carried out to examine the effects of medicinal whole-plant extracts on AD. Clinical investigations have shown that lignans, flavonoids, tannins, polyphenols, triterpenoids, sterols, and alkaloids have anti-inflammatory, antiamyloidogenic, anticholinesterase, and antioxidant properties. This review summarizes information about numerous medicinal plants and isolated compounds used in the treatment of AD and a list of further references.

Alzheimer’s disease (AD) is a severe neurodegenerative disorder of the brain that manifests as dementia, disorientation, difficulty in speech, and progressive cognitive and behavioral impairment. The emerging therapeutic approach to AD management is the inhibition of β-site APP cleaving enzyme-1 (BACE1), known to be one of the two aspartyl proteases that cleave β-amyloid precursor protein (APP). Studies confirmed the association of high BACE1 activity with the proficiency in the formation of β-amyloid-containing neurotic plaques, the characteristics of AD. Only a few FDA-approved BACE1 inhibitors are available in the market, but their adverse off-target effects limit their usage. In this paper, we have used both ligand-based and target-based approaches for drug design. The QSAR study entails creating a multivariate GA-MLR (Genetic Algorithm-Multilinear Regression) model using 552 molecules with acceptable statistical performance (R2 = 0.82, Q2loo = 0.81). According to the QSAR study, the activity has a strong link with various atoms such as aromatic carbons and ring Sulfur, acceptor atoms, sp2-hybridized oxygen, etc. Following that, a database of 26,467 food compounds was primarily used for QSAR-based virtual screening accompanied by the application of the Lipinski rule of five; the elimination of duplicates, salts, and metal derivatives resulted in a truncated dataset of 8,453 molecules. The molecular descriptor was calculated and a well-validated 6-parametric version of the QSAR model was used to predict the bioactivity of the 8,453 food compounds. Following this, the food compounds whose predicted activity (pKi) was observed above 7.0 M were further docked into the BACE1 receptor which gave rise to the Identification of 4-(3,4-Dihydroxyphenyl)-2-hydroxy-1H-phenalen-1-one (PubChem I.D: 4468; Food I.D: FDB017657) as a hit molecule (Binding Affinity = −8.9 kcal/mol, pKi = 7.97 nM, Ki = 10.715 M). Furthermore, molecular dynamics simulation for 150 ns and molecular mechanics generalized born and surface area (MMGBSA) study aided in identifying structural motifs involved in interactions with the BACE1 enzyme. Molecular docking and QSAR yielded complementary and congruent results. The validated analyses can be used to improve a drug/lead candidate’s inhibitory efficacy against the BACE1. Thus, our approach is expected to widen the field of study of repurposing nutraceuticals into neuroprotective as well as anti-cancer and anti-viral therapeutic interventions.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world, affecting an estimated 50 million individuals. The nerve cells become impaired and die due to the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs). Dementia is one of the most common symptoms seen in people with AD. Genes, lifestyle, mitochondrial dysfunction, oxidative stress, obesity, infections, and head injuries are some of the factors that can contribute to the development and progression of AD. There are just a few FDA-approved treatments without side effects in the market, and their efficacy is restricted due to their narrow target in the etiology of AD. Therefore, our aim is to identify a safe and potent treatment for Alzheimer’s disease. We chose the ursolic acid (UA) and its similar compounds as a compounds’ library. And the ChEMBL database was adopted to obtain the active and inactive chemicals against Keap1. The best Quantitative structure-activity relationship (QSAR) model was created by evaluating standard machine learning techniques, and the best model has the lowest RMSE and greatest R2 (Random Forest Regressor). We chose pIC50 of 6.5 as threshold, where the top five potent medicines (DB06841, DB04310, DB11784, DB12730, and DB12677) with the highest predicted pIC50 (7.091184, 6.900866, 6.800155, 6.768965, and 6.756439) based on QSAR analysis. Furthermore, the top five medicines utilize as ligand molecules were docked in Keap1’s binding region. The structural stability of the nominated medications was then evaluated using molecular dynamics simulations, RMSD, RMSF, Rg, and hydrogen bonding. All models are stable at 20 ns during simulation, with no major fluctuations observed. Finally, the top five medications are shown as prospective inhibitors of Keap1 and are the most promising to battle AD.

The brown dog tick (Rhipicephalus sanguineus) is the most prevalent tick in the world and a well-recognized vector of many pathogens affecting dogs and occasionally humans. Pathogens exploit tick salivary molecules for their survival and multiplication in the vector and transmission to and establishment in the hosts. Tick saliva contains various non-proteinaceous substances and secreted proteins that are differentially produced during feeding and comprise of inhibitors of blood congealing and platelet aggregation, vasodilatory and immunomodulatory substances, and compounds preventing itch and pain. One of these proteins is Evasin-1, which has a high binding affinity to certain types of chemokines. The binding of Evasin-1 to chemokines prevents the detection and immune response of the host to R. sanguineus, which may result in the successful transmission of pathogens. In this study, we screened potential Evasin-1 inhibitor based on the pharmacophore model derived from the binding site residues. Hit ligands were further screened via molecular docking and virtual ADMET prediction, which resulted in ZINC8856727 as the top ligand (binding affinity: -9.1 kcal/mol). Molecular dynamics simulation studies, coupled with MM-GBSA calculations and principal component analysis revealed that ZINC8856727 plays a vital role in the stability of Evasin-1. We recommend continuing the study by developing a formulation that serves as a potential medicine aid immune response during R. sanguineus infestation.