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Research related to boronic acids, from synthetic development to materials to drug discovery, has skyrocketed in the past 20 years. In terms of drug discovery, the incorporation of boronic acids into medicinal chemistry endeavours has seen a steady increase in recent years. In fact, the Food and Drug Administration (FDA) and Health Canada have thus far approved five boronic acid drugs, three of which were approved in the past four years, and several others are in clinical trials. Boronic acids have several desirable properties that has led to their increased use, including potentially enhancing potency of drugs and/or improving their pharmacokinetics profile. This review explores discovery processes of boronic acid drugs. It begins with a brief scope of boron in natural products and in current drugs, followed by an investigation into the various rationalizations for boronic acid incorporation and the synthetic developments that focused on facilitating their addition into organic compounds. We hope that the knowledge we have assembled in this literature review will encourage medicinal chemists to consider the potential benefits of incorporating boronic acids into their future drug discovery endeavours. Image 1 • Boronic acids can be drugs. • Bortezomib was the first approved boronic acid drug. • Boronic acid drugs are becoming more common. [ABSTRACT FROM AUTHOR]

Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CLpro (main coronaviruses cysteine-protease) has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CLpro non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CLpro. We report herein our efforts in the design and synthesis of submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform. [Display omitted] • Covalent docking was used to design SARS-CoV-2 3CLpro inhibitors. • A micromolar non-covalent SARS-CoV 3CLpro inhibitor was converted into a submicromolar SARS-CoV-2 3CLpro covalent inhibitor. • A set of warheads was evaluated and vinyl sulfonamide and alkynylamide were identified as promising warheads. • Crystallography confirmed the docking-proposed mode of binding. • SAR studies led to improved potency. [ABSTRACT FROM AUTHOR]