An international joint research group at Hokkaido University and the University of Bonn has discovered a new therapeutic target that suppresses influenza virus replication.
The seven types of anti-influenza virus drugs approved in Japan all have the property of acting on viral proteins, and have the disadvantage that drug-resistant viruses may emerge depending on the mutation of the viral gene.
On the other hand, in this research, it was clarified that the RNA methyltransferase MTr1 in infected host cells is essential for replication (proliferation) of influenza virus.By inhibiting the function of host MTr1, we found the possibility of suppressing the proliferation of influenza virus without directly acting on viral proteins.
Therefore, we screened existing drug libraries for MTr1-inhibiting compounds and searched for the most effective MTr1-inhibiting compounds exhibiting anti-influenza virus activity. TFMT) were identified.From the conformational analysis, TFMT appears to inhibit the enzymatic activity by binding to host MTr1, and is expected to suppress the cap structure modification function of host mRNA by MTr1.It was also found that influenza viruses cannot perform cap snatching (stealing the cap structure and short-chain RNA to synthesize their own mRNA) unless the cap structure is modified by MTr1. The inhibition is said to specifically suppress the synthesis of influenza virus RNA.
Anti-influenza drugs that target MTr1, a host factor, suppress viral proliferation without directly acting on viral proteins, so drug-resistant viruses are unlikely to emerge.The results of this research are expected to contribute to the development of new therapeutic agents for influenza.
Paper information:[Science] Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication
