Host-directed Inhibitors of Myxoviruses: Synthesis and in vitro Biochemical Evaluation.
Sun A, Ndungu JM, Krumm SA, Yoon JJ, Thepchatri P, Natchus M, Plemper RK, Snyder JP.
Drugs targeted to viral proteins are highly vulnerable to the development of viral resistance. One little explored approach to the treatment of viral diseases is the development of agents that target host factors required for virus replication. Myxoviruses are predominantly associated with acute disease and, thus, ideally suited for this approach since the necessary treatment time is anticipated to be limited. High-throughput screening previously identified benzimidazole 22407448 with broad anti-viral activity against different influenza virus and paramyxovirus strains. Hit to lead chemistry has generated 6p (JMN3-003) with potent antiviral activity against a panel of myxovirus family members exhibiting EC(50) values in the low nanomolar range.