tetano
Editor, Senior Moderator
J Med Chem
. 2022 Feb 25.
doi: 10.1021/acs.jmedchem.1c01257. Online ahead of print.
Discovery of Aryl Benzoyl Hydrazide Derivatives as Novel Potent Broad-Spectrum Inhibitors of Influenza A Virus RNA-Dependent RNA Polymerase (RdRp)
Xinjin Liu[SUP] 1 [/SUP], Jinsen Liang[SUP] 2 [/SUP], Yongshi Yu[SUP] 2 [/SUP], Xin Han[SUP] 2 [/SUP], Lei Yu[SUP] 1 [/SUP], Feifei Chen[SUP] 1 [/SUP], Zhichao Xu[SUP] 2 [/SUP], Qi Chen[SUP] 1 [/SUP], Mengyu Jin[SUP] 2 [/SUP], Chune Dong[SUP] 2 [/SUP], Hai-Bing Zhou[SUP] 2 3 [/SUP], Ke Lan[SUP] 1 [/SUP], Shuwen Wu[SUP] 1 [/SUP]
Affiliations
Abstract
Influenza A viruses possess a high antigenic shift, and the approved anti-influenza drugs are extremely limited, which makes the development of novel anti-influenza drugs for the clinical treatment and prevention of influenza outbreaks imperative. Herein, we report a series of novel aryl benzoyl hydrazide analogs as potent anti-influenza agents. Particularly, analogs 10b, 10c, 10g, 11p, and 11q exhibited potent inhibitory activity against the avian H5N1 flu strain with EC[SUB]50[/SUB] values ranging from 0.009 to 0.034 μM. Moreover, compound 11q exhibited nanomolar antiviral effects against both the H1N1 virus and Flu B virus and possessed good oral bioavailability and inhibitory activity against influenza A virus in a mouse model. Preliminary mechanistic studies suggested that these compounds exert anti-influenza virus effects mainly by interacting with the PB1 subunit of RNA-dependent RNA polymerase (RdRp). These results revealed that 11q has the potential to become a potent clinical candidate to combat seasonal influenza and influenza pandemics.
. 2022 Feb 25.
doi: 10.1021/acs.jmedchem.1c01257. Online ahead of print.
Discovery of Aryl Benzoyl Hydrazide Derivatives as Novel Potent Broad-Spectrum Inhibitors of Influenza A Virus RNA-Dependent RNA Polymerase (RdRp)
Xinjin Liu[SUP] 1 [/SUP], Jinsen Liang[SUP] 2 [/SUP], Yongshi Yu[SUP] 2 [/SUP], Xin Han[SUP] 2 [/SUP], Lei Yu[SUP] 1 [/SUP], Feifei Chen[SUP] 1 [/SUP], Zhichao Xu[SUP] 2 [/SUP], Qi Chen[SUP] 1 [/SUP], Mengyu Jin[SUP] 2 [/SUP], Chune Dong[SUP] 2 [/SUP], Hai-Bing Zhou[SUP] 2 3 [/SUP], Ke Lan[SUP] 1 [/SUP], Shuwen Wu[SUP] 1 [/SUP]
Affiliations
- PMID: 35212527
- DOI: 10.1021/acs.jmedchem.1c01257
Abstract
Influenza A viruses possess a high antigenic shift, and the approved anti-influenza drugs are extremely limited, which makes the development of novel anti-influenza drugs for the clinical treatment and prevention of influenza outbreaks imperative. Herein, we report a series of novel aryl benzoyl hydrazide analogs as potent anti-influenza agents. Particularly, analogs 10b, 10c, 10g, 11p, and 11q exhibited potent inhibitory activity against the avian H5N1 flu strain with EC[SUB]50[/SUB] values ranging from 0.009 to 0.034 μM. Moreover, compound 11q exhibited nanomolar antiviral effects against both the H1N1 virus and Flu B virus and possessed good oral bioavailability and inhibitory activity against influenza A virus in a mouse model. Preliminary mechanistic studies suggested that these compounds exert anti-influenza virus effects mainly by interacting with the PB1 subunit of RNA-dependent RNA polymerase (RdRp). These results revealed that 11q has the potential to become a potent clinical candidate to combat seasonal influenza and influenza pandemics.