The Editorial Board of The Journal of Antibiotics has given the 2022 JA Ōmura Award for an original article to an outstanding paper entitled “Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(Hl N1)pdm09 virus infection by interfering with virus internalization process” by Tran et al. [1]. Historically, influenza pandemics have often caused tremendous casualties: in 1918, Spanish influenza A(H1N1) led to a global pandemic, causing a catastrophe that killed an estimated 20–50 million people. In addition, several decades ago, a new influenza A(H1Nl)pdm09 virus caused the most recent global pandemic. Clinically used neuraminidase inhibitors are effective against human influenza by inhibiting the production of progeny viruses during the acute phase of infection. However, drug-resistant A(H1N1) viruses have been increasing and are now an emerging threat worldwide. Thus, new strategies are required to prepare for the next global pandemic. Tran et al. found that azithromycin (AZM), a clinically used 15-membered ring macrolide antimicrobial agent, inhibits the internalization of influenza A(H1 N1)pdm09 virus when it directly interacts with the virus before infection. As a result, replication of progeny viruses is markedly inhibited by blocking viral entry into host cells during the early stages of the infection process. Furthermore, intranasal administration of AZM to mice infected with A(H1Nl)pdm09 virus successfully reduced the amount of virus in the lungs and alleviated hypothermia induced by the infection. Because developing new anti-influenza drugs from scratch is a time-consuming process, repositioning of approved drugs is one of the most effective strategies to identify new anti-influenza drugs in a short time. AZM may be prescribed to prevent both primary infection by influenza A virus and secondary infection by bacteria.

The 2022 winner of the Ōmura Award for an original review article is “Splicing Modulators: on the Way from Nature to the Clinic” by Schneider-Poetsch et al. [2]. This review article examines more than two decades of research on the discovery and application of splicing modulators and their function as chemical probes and drug candidates. Splicing is a fundamental process in eukaryotes, which is not found in prokaryotes. Thus, it is not surprising that complex cytotoxic antibiotics targeting this mechanism have evolved. Antibiotic classes examined in this review include spliceostatins, pladienolides, and herboxidienes. Synthetic analogs of these classes have become powerful probes for studying splicing and mRNA processing. The related splice-site modifiers NVS-SM1/Branaplam and Risdiplam, which avoid overt toxicity and have shown impressive therapeutic benefits in the treatment of splicing disorders, are also discussed.

The review covers the initial splicing inhibitor discoveries and subsequent efforts to optimize the modulators, the identification of the spliceosome and its function, the cellular effects of splicing modulation, ongoing clinical trials, new approaches such as the use of targeted protein degradation to manipulate this pathway, and RNA-binding modulators exemplified by those that have been successfully developed to treat spinal muscular atrophy caused by splice variants. It concludes with an outlook for the future of the field.

This outstanding review is highly recommended to those interested in learning more about the current state of the art in research and development surrounding the discovery and development of splicing modulators.