Betz Ulrich A K, Garces Robert, Beier Norbert, Lindemann Sven, Wolff Karen C, Riva Laura, Kirkpatrick Melanie G, Gebara-Lamb Amal, McNamara Case W, Damoiseaux Robert, Gomperts Brigitte N, Arumugaswami Vaithilingaraja, Strand Mårten, Gwon Yongdae, Elofsson Mikael, Evander Magnus
Merck KGaA, 64293 Darmstadt, Germany.
EMD Serono Research & Development Institute, Inc., Billerica, MA 01821, USA.
Viruses. 2025 Mar 7;17(3):385. doi: 10.3390/v17030385.
The pandemic threat from newly emerging viral diseases constitutes a major unsolved issue for global health. Antiviral therapy can play an important role in treating and preventing the spread of unprecedented viral infections. A repository of compounds exhibiting broad-spectrum antiviral activity against a series of different viral families would be an invaluable asset to be prepared for future pandemic threats. Utilizing an open innovation crowd-sourcing paradigm, we were able to identify a compound class of diphenylureas that exhibits in vitro antiviral activity against multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adenovirus, dengue virus, herpes, and influenza viruses. Compound 4 among the series exhibits strong activity against dengue virus, a growing global health problem with high medical need and no approved antiviral drug. The compounds are active against SARS-CoV-2 in a primary human stem cell-based mucociliary airway epithelium model and also active in vivo, as shown in a murine SARS-CoV-2 infection model. These results demonstrate the potential of the chemical class as antivirals on the one hand and the power of open innovation, crowd-sourcing, and repurposing on the other hand.
新出现的病毒性疾病构成的大流行威胁是全球健康领域一个重大的未解决问题。抗病毒疗法在治疗和预防前所未有的病毒感染传播方面可发挥重要作用。拥有一系列针对不同病毒家族具有广谱抗病毒活性的化合物库，将是应对未来大流行威胁的一项宝贵资产。利用开放式创新众包模式，我们能够鉴定出一类二苯基脲化合物，它们在体外对多种病毒具有抗病毒活性，包括严重急性呼吸综合征冠状病毒2（SARS-CoV-2）、腺病毒、登革病毒、疱疹病毒和流感病毒。该系列中的化合物4对登革病毒具有强大活性，登革病毒是一个日益严重的全球健康问题，医疗需求高且尚无获批的抗病毒药物。这些化合物在基于原代人干细胞的黏液纤毛气道上皮模型中对SARS-CoV-2具有活性，并且在体内也有活性，如在小鼠SARS-CoV-2感染模型中所示。这些结果一方面证明了这类化学物质作为抗病毒药物的潜力，另一方面证明了开放式创新、众包和药物重新利用的力量。
