The Role of Natural Products as Sources of Therapeutic Agents for Innovative Drug Discovery

Emerging threats to human health require a concerted effort in search of both preventive and treatment strategies, placing natural products at the center of efforts to obtain new therapies and reduce disease spread and associated mortality. The therapeutic value of compounds found in plants has been known for ages, resulting in their utilization in homes and in clinics for the treatment of many ailments ranging from common headache to serious conditions such as wounds. Despite the advancement observed in the world, plant based medicines are still being used to treat many pathological conditions or are used as alternatives to modern medicines. In most cases, these natural products or plant-based medicines are used in an un-purified state as extracts. A lot of research is underway to identify and purify the active compounds responsible for the healing process. Some of the current drugs used in clinics have their origins as natural products or came from plant extracts. In addition, several synthetic analogues are natural product-based or plant-based. With the emergence of novel infectious agents such as the SARS-CoV-2 in addition to already burdensome diseases such as diabetes, cancer, tuberculosis and HIV/AIDS, there is need to come up with new drugs that can cure these conditions. Natural products offer an opportunity to discover new compounds that can be converted into drugs given their chemical structure diversity. Advances in analytical processes make drug discovery a multi-dimensional process involving computational designing and testing and eventual laboratory screening of potential drug candidates. Lead compounds will then be evaluated for safety, pharmacokinetics and efficacy. New technologies including Artificial Intelligence, better organ and tissue models such as organoids allow virtual screening, automation and high-throughput screening to be part of drug discovery. The use of bioinformatics and computation means that drug discovery can be a fast and efficient process and enable the use of natural products structures to obtain novel drugs. The removal of potential bottlenecks resulting in minimal false positive leads in drug development has enabled an efficient system of drug discovery. This review describes the biosynthesis and screening of natural products during drug discovery as well as methods used in studying natural products.

Recent Trends in Multipotent Human Mesenchymal Stem/Stromal Cells: Learning from History and Advancing Clinical Applications.

Early cell biology reports demonstrated the presence of cells with stem-like properties in bone marrow, with both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multilineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and versatile potentials, MSCs are leveraged in many applications in medicine such as oncology, bioprinting, and as recent as therapeutics discovery and innovation for COVID-19. To date, studies indicate that MSCs have varied differentiation capabilities into different cell types, and demonstrate immunomodulating and anti-inflammatory properties. Different microenvironments or niche for MSCs and their resulting heterogeneity may influence attendant cellular behavior and differentiation capacity. The potential clinical applications of MSCs and exosomes derived from these cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. There is ample reason to think, as discussed in this expert review that the future looks bright and promising for MSC research, with many clinical trials under way to ascertain their clinical utility. This review provides a synthesis of the latest advances and trends in MSC research to allow for broad and critically informed use of MSCs. Early observations of the presence of these cells in the bone marrow and their remarkable differentiation capabilities and immunomodulation are also presented.

The Role of Viruses in Carcinogenesis and Molecular Targeting: From Infection to Being a Component of the Tumor Microenvironment.

About a tenth of all cancers are caused by viruses or associated with viral infection. Recent global events including the coronavirus disease-2019 (COVID-19) pandemic means that human encounter with viruses is increased. Cancer development in individuals with viral infection can take many years after infection, demonstrating that the involvement of viruses in cancer development is a long and complex process. This complexity emanates from individual genetic heterogeneity and the many steps involved in cancer development owing to viruses. The process of tumorigenesis is driven by the complex interaction between several viral factors and host factors leading to the creation of a tumor microenvironment (TME) that is ideal and promotes tumor formation. Viruses associated with human cancers ensure their survival and proliferation through activation of several cellular processes including inflammation, migration, and invasion, resistance to apoptosis and growth suppressors. In addition, most human oncoviruses evade immune detection and can activate signaling cascades including the PI3K-Akt-mTOR, Notch and Wnt pathways associated with enhanced proliferation and angiogenesis. This expert review examines and synthesizes the multiple biological factors related to oncoviruses, and the signaling cascades activated by these viruses contributing to viral oncogenesis. In particular, I examine and review the Epstein-Barr virus, human papillomaviruses, and Kaposi's sarcoma herpes virus in a context of cancer pathogenesis. I conclude with a future outlook on therapeutic targeting of the viruses and their associated oncogenic pathways within the TME. These anticancer strategies can be in the form of, but not limited to, antibodies and inhibitors.

Coronavirus Disease 19 and Future Ecological Crises: Hopes from Epigenomics and Unraveling Genome Regulation in Humans and Infectious Agents.

With coronavirus disease 19 (COVID-19), we have witnessed a shift from public health to planetary health and a growing recognition of the importance of systems science in developing effective solutions against pandemics in the 21st century. COVID-19 and the history of frequent infectious outbreaks in the last two decades suggest that COVID-19 is likely a dry run for future ecological crises. Now is the right time to plan ahead and deploy the armamentarium of systems science scholarship for planetary health. The science of epigenomics, which investigates both genetic and nongenetic traits regarding heritable phenotypic alterations, and new approaches to understanding genome regulation in humans and pathogens offer veritable prospects to boost the global scientific capacities to innovate therapeutics and diagnostics against novel and existing infectious agents. Several reversible epigenetic alterations, such as chromatin remodeling and histone methylation, control and influence gene expression. COVID-19 lethality is linked, in part, to the cytokine storm, age, and status of the immune system in a given person. Additionally, due to reduced human mobility and daily activities, effects of the pandemic on the environment have been both positive and negative. For example, reduction in environmental pollution and lesser extraction from nature have potential positive corollaries on water and air quality. Negative effects include pollution as plastics and other materials were disposed in unconventional places and spaces in the course of the pandemic. I discuss the opportunities and challenges associated with the science of epigenomics, specifically with an eye to inform and prevent future ecological crises and pandemics that are looming on the horizon in the 21st century. In particular, this article underscores that epigenetics of both viruses and the host may influence virus infectivity and severity of attendant disease.

Implementing Artificial Intelligence and Digital Health in Resource-Limited Settings? Top 10 Lessons We Learned in Congenital Heart Defects and Cardiology.

Artificial intelligence (AI) is one of the key drivers of digital health. Digital health and AI applications in medicine and biology are emerging worldwide, not only in resource-rich but also resource-limited regions. AI predates to the mid-20th century, but the current wave of AI builds in part on machine learning (ML), big data, and algorithms that can learn from massive amounts of online user data from patients or healthy persons. There are lessons to be learned from AI applications in different medical specialties and across developed and resource-limited contexts. A case in point is congenital heart defects (CHDs) that continue to plague sub-Saharan Africa, which calls for innovative approaches to improve risk prediction and performance of the available diagnostics. Beyond CHDs, AI in cardiology is a promising context as well. The current suite of digital health applications in CHD and cardiology include complementary technologies such as neural networks, ML, natural language processing and deep learning, not to mention embedded digital sensors. Algorithms that build on these advances are beginning to complement traditional medical expertise while inviting us to redefine the concepts and definitions of expertise in molecular diagnostics and precision medicine. We examine and share here the lessons learned in current attempts to implement AI and digital health in CHD for precision risk prediction and diagnosis in resource-limited settings. These top 10 lessons on AI and digital health summarized in this expert review are relevant broadly beyond CHD in cardiology and medical innovations. As with AI itself that calls for systems approaches to data capture, analysis, and interpretation, both developed and developing countries can usefully learn from their respective experiences as digital health continues to evolve worldwide.

Coronavirus Disease-2019 Treatment Strategies Targeting Interleukin-6 Signaling and Herbal Medicine.

Coronavirus disease-2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is evolving across the world and new treatments are urgently needed as with vaccines to prevent the illness and stem the contagion. The virus affects not only the lungs but also other tissues, thus lending support to the idea that COVID-19 is a systemic disease. The current vaccine and treatment development strategies ought to consider such systems medicine perspectives rather than a narrower focus on the lung infection only. COVID-19 is associated with elevated levels of the inflammatory cytokines such as interleukin-6 (IL-6), IL-10, and interferon-gamma (IFN-γ). Elevated levels of cytokines and the cytokine storm have been linked to fatal disease. This suggests new therapeutic strategies through blocking the cytokine storm. IL-6 is one of the major cytokines associated with the cytokine storm. IL-6 is also known to display pleiotropic/diverse pathophysiological effects. We suggest the blockage of IL-6 signaling and its downstream mediators such as Janus kinases (JAKs), and signal transducer and activators of transcription (STATs) offer potential hope for the treatment of severe cases of COVID-19. Thus, repurposing of already approved IL-6-JAK-STAT signaling inhibitors as well as other anti-inflammatory drugs, including dexamethasone, is under development for severe COVID-19 cases. We conclude this expert review by highlighting the potential role of precision herbal medicines, for example, the Cannabis sativa, provided that omics technologies can be utilized to build a robust scientific evidence base on their clinical safety and efficacy. Precision herbal medicine buttressed by omics systems science would also help identify new molecular targets for drug discovery against COVID-19.

COVID-19 Pandemic and Africa: From the Situation in Zimbabwe to a Case for Precision Herbal Medicine.

This opinion commentary on the coronavirus disease 2019 (COVID-19) pandemic brings together observations from Zimbabwe specifically, and Africa broadly, drawing from the fields of pharmacogenomics, precision herbal medicine, and responsible innovation so as to respond to the pandemic in ways that are efficient, critically informed, principled, and responsive to needs in rural and urban communities across Africa. With new findings suggesting that COVID-19 is a systemic disease, impacting the respiratory system and beyond in some individuals, we need new molecular targets for therapeutics innovation more than ever. We argue that the current pandemic will likely strip the limited resources from other diseases such as malaria, human immunodeficiency virus (HIV) infection, and among others affecting the African continent. Hence, we need to address not only COVID-19 but also its broader health care and societal impacts in Africa. Extensive diagnostic testing to trace and isolate the COVID-19 cases as well as basic income and economic support for those who are unable to work will be needed. A critically informed and democratic governance that builds on transparency and trust for the elected leaders is crucial. Finally, the pandemic offers a silver lining for Africa: the prospects to integrate omics research with long-standing expertise in herbal medicine in Africa, thus accelerating the advances toward novel molecular therapeutic targets for COVID-19 and precision herbal medicine worldwide.