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ABSTRACTIntroductionProtein kinases (PKs) play key roles in cellular signaling and regulation cascades and therefore are listed among the most investigated enzymes with the intent to develop drugs that are able to modulate their catalytic features. Specifically, PKs are involved in chronic diseases of large impact in the society such as cancers and neurodegeneration. Since the approval of Fasudil for the management of cerebral vasospasm, frantic efforts are currently ongoing for the development of selective PK-modulating agents.Areas coveredA selection of the most relevant patents in the European Patent Office for biomedical innovation and/or industrial development covering the years 2020–2023 on PK modulators either of the antibody and small-molecule type is reported. In addition to the examined patents, we also reported the contributions claiming the use of antibody-targeted PKs for lab bench identification kits.Expert opinionThe field of PK modulators for biomedical purposes is particularly crowded with contributions, making it rich in valuable information for the development of potential drugs. An emerging frontier is represented by PK activators that aims to complement the use of PK inhibitors with the final intent of finely adjusting any PK-related disruption responsible for triggering any disease.

ABSTRACTIntroductionNeisseria gonorrhoeaeis a common sexually transmitted disease connected with extensive drug resistance to many antibiotics. Presently, only expanded spectrum cephalosporins (ceftriaxone and cefixime) and azithromycin remain useful for its management.Areas coveredNew chemotypes for the classical antibiotic drug target gyrase/topoisomerase IV afforded inhibitors with potent binding to these enzymes, with an inhibition mechanism distinct from that of fluoroquinolones, and thus less prone to mutations. The α-carbonic anhydrase from the genome of this bacterium (NgCAα) was also validated as an antibacterial target.Expert opinionBy exploiting different subunits from the gyrase/topoisomerase IV as well as new chemotypes, two new antibiotics reached Phase II/III clinical trials, zoliflodacin and gepotidacin. They possess a novel inhibition mechanism, binding in distinct parts of the enzyme compared to the fluoroquinolones. Other chemotypes with inhibitory activity in these enzymes were also reported. NgCAα inhibitors belonging to a variety of classes were obtained, with several sulfonamides showing MIC values in the range of 0.25–4 µg/mL and significant activity in animal models of this infection. Acetazolamide and similar CA inhibitors might thus be repurposed as antiinfectives. The scientific/patent literature has been searched for on PubMed, ScienceDirect, Espacenet, and PatentGuru, from 2016 to 2024.

ABSTRACTIntroductionCarbonic anhydrases (CAs, EC 4.2.1.1) play a pivotal role in the regulation of carbon dioxide , bicarbonate, and hydrogen ions within bacterial cells, ensuring pH homeostasis and facilitating energy production. We conducted a systematic literature search (PubMed, Web of Science, and Google Scholar) to examine the intricate interplay between CAs and bacterial metabolism, revealing the potential of CA inhibitors (CAIs) as innovative therapeutic agents against pathogenic bacteria.Area coveredInhibition of bacterial CAs was explored in various pathogens, emphasizing the CA roles in microbial virulence, survival, and adaptability. Escherichia coli, a valid and convenient model microorganism, was recently used to investigate the effects of acetazolamide (AAZ) on the bacterial life cycle. Furthermore, the effectiveness of CAIs against pathogenic bacteria has been further substantiated for Vancomycin-Resistant Enterococci (VRE) and antibiotic-resistant Neisseria gonorrhoeaestrains.Expert opinionCAIs target bacterial metabolic pathways, offering alternatives to conventional therapies. They hold promise against drug-resistant microorganisms such as VRE and N.gonorrhoeaestrains. CAIs offer promising avenues for addressing antibiotic resistance and underscore their potential as novel antibacterial agents. Recognizing the central role of CAs in bacterial growth and pathogenicity will pave the way for innovative infection control and treatment strategies possibly also for other antibiotic resistant species.

ABSTRACTIntroductionThe two cysteine proteases from the coronaviruses, which produced deadly outbreaks in the last two decades, SARS CoV-1/2, and MERS, the main protease (Mpro) and the papain-like protease (PLP) are conserved among the three pathogens and started to be considered as exciting drug targets for developing antivirals.Areas coveredWe review the drug design landscape in the scientific and patent literature to design peptidomimetic and non-peptidomimetic protease inhibitors (PIs) targeting these proteins.Expert opinionThe X-ray crystal structures of some of these proteases, alone and in complex with various inhibitors, were crucial for the discovery of effective such compounds, some of which also showed considerable antiviral activity and are considered preclinical candidates to fight these emerging infections, which in the case of Covid-19 already provoked an unprecedented worldwide pandemic.