Globally, malignancies cause one out of six mortalities, which is a serious health problem. Cancer therapy has always been challenging, apart from major advances in immunotherapies, stem cell transplantation, targeted therapies, hormonal therapies, precision medicine, and palliative care, and traditional therapies such as surgery, radiation therapy, and chemotherapy. Natural products are integral to the development of innovative anticancer drugs in cancer research, offering the scientific community the possibility of exploring novel natural compounds against cancers. The role of natural products like Vincristine and Vinblastine has been thoroughly implicated in the management of leukemia and Hodgkin’s disease. The computational method is the initial key approach in drug discovery, among various approaches. This review investigates the synergy between natural products and computational techniques, and highlights their significance in the drug discovery process. The transition from computational to experimental validation has been highlighted through in vitro and in vivo studies, with examples such as betulinic acid and withaferin A. The path toward therapeutic applications have been demonstrated through clinical studies of compounds such as silvestrol and artemisinin, from preclinical investigations to clinical trials. This article also addresses the challenges and limitations in the development of natural products as potential anti-cancer drugs. Moreover, the integration of deep learning and artificial intelligence with traditional computational drug discovery methods may be useful for enhancing the anticancer potential of natural products.

Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a key role in the coordination of rapid gene induction during the inflammatory response. Using a high-throughput reporter assay we explored the function of Epromoters in response to type I interferon. We find that clusters of IFNa-induced genes are frequently associated with Epromoters and that these regulatory elements preferentially recruit the STAT1/2 and IRF transcription factors and distally regulate the activation of interferon-response genes. Consistently, we identified and validated the involvement of Epromoter-containing clusters in the regulation of LPS-stimulated macrophages. Our findings suggest that Epromoters function as a local hub recruiting the key TFs required for coordinated regulation of gene clusters during the inflammatory response.

Young age, female sex, absence of comorbidities, and prior infection or vaccination are known epidemiological barriers for contracting the new infection and/or increased disease severity. Demographic trends from the recent coronavirus disease 2019 waves, which are believed to be driven by newer severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants, indicate that the aforementioned epidemiological barriers are being breached and a larger number of younger and healthy individuals are developing severe disease. The new SARS‐CoV‐2 variants have key mutations that can induce significant changes in the virus‐host interactions. Recent studies report that, some of these mutations, singly or in a group, enhance key mechanisms, such as binding of the receptor‐binding domain (RBD) of the viral spike protein with the angiotensin‐converting enzyme 2 (ACE2) receptor in the host‐cells, increase the glycosylation of spike protein at the antigenic sites, and enhance the proteolytic cleavage of the spike protein, thus leading to improved host‐cell entry and the replication of the virus. The putative changes in the virus–host interactions imparted by the mutations in the RBD sequence can potentially be the reason behind the breach of the observed epidemiological barriers. Susceptibility for contracting SARS‐CoV‐2 infection and the disease outcomes are known to be influenced by host‐cell expressions of ACE2 and other proteases. The new variants can act more efficiently, and even with the lesser availability of the viral entry‐receptor and the associated proteases, can have more efficient host‐cell entry and greater replication resulting in high viral loads and prolonged viral shedding, widespread tissue‐injury, and severe inflammation leading to increased transmissibility and lethality. Furthermore, the accumulating evidence shows that multiple new variants have reduced neutralization by both, natural and vaccine‐acquired antibodies, indicating that repeated and vaccine breakthrough infections may arise as serious health concerns in the ongoing pandemic.