Bacillus thuringiensis (Bt)-based products are the most successful microbial insecticides to date. This entomopathogenic bacterium produces different kinds of proteins whose specific toxicity has been shown against a wide range of insect orders, nematodes, mites, protozoa, and human cancer cells. Some of these proteins are accumulated in parasporal crystals during the sporulation phase (Cry and Cyt proteins), whereas other proteins are secreted in the vegetative phase of growth (Vip and Sip toxins). Currently, insecticidal proteins belonging to different groups (Cry and Vip3 proteins) are widely used to control insect pests and vectors both in formulated sprays and in transgenic crops (the so-called Bt crops). Despite the extensive use of these proteins in insect pest control, especially Cry and Vip3, their mode of action is not completely understood. The aim of this Special Issue was to gather information that could summarize (in the form of review papers) or expand (research papers) the knowledge of the structure and function of Bt proteins, as well as shed light on their mode of action, especially regarding the insect receptors. This subject has generated great interest, and this interest has been materialized into the 18 papers of important scientific value in the field (5 reviews and 13 research papers) that have been compiled in this issue.

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The aim of this Special Issue reprint is to introduce the reader to the latest biotechnological approaches used in crop protection by employing Bacillus thuringiensis (Bt) and its invertebrate active proteins. This Special Issue brought together descriptions of novel isolated Bt strains and insecticidal proteins with previously undescribed biocidal activities, reflecting the ongoing quest for innovation in crop protection to overcome insect resistance and expanding host ranges. Altogether, the content of this reprint will offer multiple benefits for users in agribusiness, the economy, and wider society.

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The present book, a reprint of the Molecules Special Issue "Insecticide, Acaricide, Repellent and Antimicrobial Development", presents key advances in the development of effective and eco-friendly insecticides, acaricides, repellents, and antimicrobials, including products of natural origin.

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We are very pleased to introduce the Book Version of our Special Issue in Molecules dedicated to the memory of the late Professor Dr. Charles D. Hufford. The issue has been a huge success, with 22 full-length peer-reviewed papers and a tribute by Professor Alice M.Clark. Authors, reviewers, and collaborators from many countries across the worldhave contributed to this endeavour, and we are truly grateful to all. This Special Issue isrepresentative of the broad impact that “Charlie” had on the field of bioactive naturalproducts. This Special Issue comprises papers from Professor Hufford’s former students,colleagues, and collaborators throughout the world who have utilized a wide array ofstate-of-the-art techniques to examine diverse natural sources to isolate and identify avariety of natural products with a wide spectrum of biological activities, including somenew microbial transformations and insights into bioactive molecules. Many new bioactive compounds are described and reported here for the first time. Bioactivities reportedinclude cytotoxicity, antimicrobial activity, anti-inflammatory activity, antileishmanialactivity, antitrypanosomal activity, antimalarial activity, analgesic activity, and beneficialliver activities, just to name a few. This Special Issue will undoubtedly have a lasting impact on the field of bioactive natural products, as exemplified by the career of Dr. Hufford.Lastly, without the timely and outstanding contributions from all of you, this Special Issue would not have been possible. We thank you all very much for your contributions and your time devoted to this Special Issue in memory of a special person. Finally, we express ourgratitude and thanks to the journal Molecules and their excellent team of expert reviewers for giving us the support and opportunity to make this Special Issue a huge success!

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The Book covers this whole field, from the discovery of structurally new and bioactive natural products (including biomacromolecules), from marine macro-/micro-organisms, to the pharmacodynamics, pharmacokinetics, metabolisms, and mechanisms of marine-derived lead compounds, both in vitro and in vivo, along with the synthesis and/or structural optimization of marine-derived lead compounds and their structure–activity relationships. Taken together, this Special Issue reprint not only provides inspiration for the discovery of marine-derived novel bioactive compounds, but also sheds light on the further research and development of marine candidate drugs.

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The global biodiversity and climate emergencies demand transformative changes to human activities. For example, food production relies on synthetic, industrial and non-sustainable products for managing pests, weeds and diseases of crops. Sustainable farming requires approaches to managing these agricultural constraints that are more environmentally benign and work with rather than against nature. Increasing pressure on synthetic products has reinvigorated efforts to identify alternative pest management options, including plant-based solutions that are environmentally benign and can be tailored to different farmers’ needs, from commercial to small holder and subsistence farming. Botanical insecticides and pesticidal plants can offer a novel, effective and more sustainable alternative to synthetic products for controlling pests, diseases and weeds. This Special Issue reviews and reports the latest developments in plant-based pesticides from identification of bioactive plant chemicals, mechanisms of activity and validation of their use in horticulture and disease vector control. Other work reports applications in rice weeds, combination biopesticides and how chemistry varies spatially and influences the effectiveness of botanicals in different locations. Three reviews assess wider questions around the potential of plant-based pest management to address the global challenges of new, invasive and established crop pests and as-yet underexploited pesticidal plants.

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Proteins represent one of the most abundant classes of biological macromolecules and play crucial roles in a vast array of physiological and pathological processes. The knowledge of the 3D structure of a protein, as well as the possible conformational transitions occurring upon interaction with diverse ligands, are essential to fully comprehend its biological function.In addition to globular, well-folded proteins, over the past few years, intrinsically disordered proteins (IDPs) have received a lot of attention. IDPs are usually aggregation-prone and may form toxic amyloid fibers and oligomers associated with several human pathologies. Peptides are smaller in size than proteins but similarly represent key elements of cells. A few peptides are able to work as tumor markers and find applications in the diagnostic and therapeutic fields. The conformational analysis of bioactive peptides is important to design novel potential drugs acting as selective modulators of specific receptors or enzymes. Nevertheless, synthetic peptides reproducing different protein fragments have frequently been implemented as model systems in folding studies relying on structural investigations in water and/or other environments.This book contains contributions (seven original research articles and five reviews published in the journal Molecules) on the above-described topics and, in detail, it includes structural studies on globular folded proteins, IDPs and bioactive peptides. These works were conducted usingdifferent experimental methods.

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Essential oils (EOs) and microbial/plant-based volatile organic compounds (VOCs) are being used in an increasing number of sectors such as health, cosmetics, the food industry and, more recently, agronomy. In agronomy, they are employed as bio-herbicides and bio-pesticides due to their their insecticidal, antifungal, and bactericidal effects. Several EO-based bio-pesticides are already registered. Essential oils and other VOCs are 100% bio-based and present numerous additional advantages. They contain a great number of structurally diverse compounds that frequently act in synergy; they are thus less subject to resistance. As highly volatile compounds are found in EOs and VOCs, they typically cause no residue problems in food products or in soils. Indeed, the supply of EOs can be really challenging because they are frequently produced in restricted areas of the world with prices and chemical composition fluctuations. Besides, while the high volatility of EOs and VOCs is interesting for some specific applications, it can be a problem when developing a bio-pesticide with long lasting effects. Finally, EOs are frequently phytotoxic, which is perfect for herbicide formulations, but not for other applications. In both cases, the development of a proper formulation is essential. Owing to the current attraction for natural products, a better understanding of their modes of biological action is of importance for the development of new and optimal applications.

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