Screening Anti-influenza Agents that Target Avian Influenza Polymerase Protein PAC from Plant Extracts Based on NMR Methods

Abstract

The highly pathogenic avian influenza A virus poses a global threat to human health. Avian influenza RNA polymerase protein PAC was used in the screening of two herbal plant extracts for anti-influenza agents. As a result, chlorogenic acid was identified to be PAC ligand and was discovered to inhibit polymerase activity. Hence, this work revealed a potential anti-influenza lead compound and provided an important step in the discovery of new anti-influenza drugs.

Material basis studies of anti‐Influenza A active ingredients in Tanreqing Injection

“…In addition, the main component of L. japonica Thunb., caffeic acid (or its analogs), suppressed influenza A virus multiplication in MDCK cells as a dual inhibitor of cyclooxygenase‐2 and NF‐ κ B (Cai et al, ; Lei, Wei, Tao, Rui, & Shi, ; Utsunomiya et al, ). Moreover, chlorogenic acid was identified to inhibit avian influenza polymerase activity as a ligand (Li et al, ). In addition, ursodeoxycholic acid (Willart et al, ) and chenodeoxycholic acid (Shaik, Panati, Narasimha, & Narala, ) had an anti‐inflammatory effect in airway inflammation in a murine model.…”

Screen Anti-influenza Lead Compounds That Target the PAC Subunit of H5N1 Viral RNA Polymerase

“…In previous work, we have discovered chlorogenic acid (CA) from Flos Lonicera Japonica and Eucommia Ulmoides Oliv extracts as a PA C ligand and potential anti-influenza active compound [17] . Herein, nine CA derivatives, the principal active components of several anti-influenza traditional Chinese medicines (e.g., Flos Lonicera Japonica [20] , Stemona Japonica [21] ), were tested ( Table 1 , Table S1 ).…”

“…This conservation indicates that the anti-influenza agents targeting the PA subunit may be effective against most influenza strains and less susceptible to drug resistance [10] – [12] . Actually, some works have been done in the anti-influenza molecule screening targeting at PA [17] – [19] . In the pursuit of novel anti-influenza agents, we present a screen against the carboxyl-terminal domain of PA (termed PA C , residues 257–716).…”

Structure-based drug discovery for combating influenza virus by targeting the PA–PB1 interaction

“…According to this model, the binding between PA and PB1 involves hydrogen bonds and hydrophobic contacts, where the N-terminal residues of PB1 are inserted in the pocket of PA 15 . To explore PA-targeting inhibitors, various techniques such as NMR method 18 , phylogenetic analysis 19 and high-throughput ELISA-based screening 20 , 21 have been reported.…”