tetano
Editor, Senior Moderator
Drug Discov Today
. 2022 Mar 2;S1359-6446(22)00085-X.
doi: 10.1016/j.drudis.2022.02.024. Online ahead of print.
Approaches for discovery of small-molecular antivirals targeting to influenza A virus PB2 subunit
Wenteng Chen[SUP] 1 [/SUP], Jiaan Shao[SUP] 2 [/SUP], Zhimin Ying[SUP] 3 [/SUP], Yushen Du[SUP] 4 [/SUP], Yongping Yu[SUP] 5 [/SUP]
Affiliations
Abstract
Influenza is an acute respiratory infectious disease caused by influenza virus, leading to huge morbidity and mortality in humans worldwide. Despite the availability of antivirals in the clinic, the emergence of resistant strains calls for antivirals with novel mechanisms of action. The PB2 subunit of the influenza A virus polymerase is a promising target because of its vital role in the 'cap-snatching' mechanism. In this review, we summarize the technologies and medicinal chemistry strategies for hit identification, hit-to-lead and lead-to-candidate optimization, and current challenges in PB2 inhibitor development, as well as offering insights for the fight against drug resistance.
Keywords: Influenza virus; PB2 subunit; cap-snatching mechanism; drug discovery; medicinal chemistry strategies.
. 2022 Mar 2;S1359-6446(22)00085-X.
doi: 10.1016/j.drudis.2022.02.024. Online ahead of print.
Approaches for discovery of small-molecular antivirals targeting to influenza A virus PB2 subunit
Wenteng Chen[SUP] 1 [/SUP], Jiaan Shao[SUP] 2 [/SUP], Zhimin Ying[SUP] 3 [/SUP], Yushen Du[SUP] 4 [/SUP], Yongping Yu[SUP] 5 [/SUP]
Affiliations
- PMID: 35247593
- DOI: 10.1016/j.drudis.2022.02.024
Abstract
Influenza is an acute respiratory infectious disease caused by influenza virus, leading to huge morbidity and mortality in humans worldwide. Despite the availability of antivirals in the clinic, the emergence of resistant strains calls for antivirals with novel mechanisms of action. The PB2 subunit of the influenza A virus polymerase is a promising target because of its vital role in the 'cap-snatching' mechanism. In this review, we summarize the technologies and medicinal chemistry strategies for hit identification, hit-to-lead and lead-to-candidate optimization, and current challenges in PB2 inhibitor development, as well as offering insights for the fight against drug resistance.
Keywords: Influenza virus; PB2 subunit; cap-snatching mechanism; drug discovery; medicinal chemistry strategies.