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Last update 08 May 2025

PA protein

Last update 08 May 2025

Basic Info

Synonyms-

Introduction

Plays an essential role in viral RNA transcription and replication by forming the heterotrimeric polymerase complex together with PB1 and PB2 subunits. The complex transcribes viral mRNAs by using a unique mechanism called cap-snatching. It consists in the hijacking and cleavage of host capped pre-mRNAs. These short capped RNAs are then used as primers for viral mRNAs. The PB2 subunit is responsible for the binding of the 5' cap of cellular pre-mRNAs which are subsequently cleaved after 10-13 nucleotides by the PA subunit that carries the endonuclease activity.

Drugs associated with PA protein

Suraxavir Marboxil

Target

PA protein

Mechanism

PA protein inhibitors

Active Org.

Ginkgo Pharmaceutical (Suzhou) Co., Ltd. [+2]

Originator Org.

Ginkgo Pharmaceutical (Suzhou) Co., Ltd.

Active Indication

Influenza A virus infection [+3]

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

China

First Approval Date25 Mar 2025

ADC-189

Target

CEN x PA protein

Mechanism

CEN inhibitors [+1]

Active Org.

Jiaxing'an Dikang Biotechnology Co., Ltd. [+2]

Originator Org.

Jiaxing'an Dikang Biotechnology Co., Ltd.

Active Indication

Influenza A virus infection [+2]

Inactive Indication-

Drug Highest PhaseNDA/BLA

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ZX-7101A

Target

Endonuclease x PA protein

Mechanism

Endonuclease inhibitors [+1]

Active Org.

Jiangsu Xuantai Pharmaceutical Co., Ltd [+1]

Originator Org.

Nanjing Zenshine Pharmaceuticals Co., Ltd.

Active Indication

Influenza, Human [+1]

Inactive Indication-

Drug Highest PhaseNDA/BLA

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with PA protein

NCT06841926

/ Not yet recruitingPhase 1

A Study to Evaluate the Pharmacokinetics of ZX-7101A for Suspension Versus Tablets in a Single Oral Administration Under Fasting Conditions in Healthy Chinese Adult Male Subjects

Study to evaluate the pharmacokinetics and relative bioavailability of metabolites in healthy Chinese adult males

Start Date28 Feb 2025

Sponsor / Collaborator

Nanjing Zenshine Pharmaceuticals Co., Ltd.

CTR20244595

/ CompletedPhase 1

在中国健康受试者空腹状态下单次口服GP681干混悬剂（规格：20mg）及GP681片（规格：20mg）的生物利用度研究

[Translation] Study on the bioavailability of GP681 dry suspension (specification: 20 mg) and GP681 tablets (specification: 20 mg) after a single oral administration in Chinese healthy subjects under fasting state

主要研究目的评价中国健康男性受试者单次口服受试制剂GP681干混悬剂（规格：20mg/袋，生产厂家：江西科睿药业有限公司）及参比制剂GP681片（规格：20mg/片，生产厂家：江西科睿药业有限公司）后的相对生物利用度和药代动力学特征。次要研究目的 1）评价受试制剂GP681干混悬剂（规格：20mg/袋）及参比制剂GP681片（规格：20mg/片）在中国健康男性受试者中单次口服给药的安全性； 2）评价受试者服用受试制剂GP681干混悬剂后的口感（适口性）。

[Translation]

Main study objectives To evaluate the relative bioavailability and pharmacokinetic characteristics of the test preparation GP681 dry suspension (specification: 20 mg/bag, manufacturer: Jiangxi Kerui Pharmaceutical Co., Ltd.) and the reference preparation GP681 tablets (specification: 20 mg/tablet, manufacturer: Jiangxi Kerui Pharmaceutical Co., Ltd.) after a single oral administration in healthy Chinese male subjects. Secondary study objectives 1) To evaluate the safety of single oral administration of the test preparation GP681 dry suspension (specification: 20 mg/bag) and the reference preparation GP681 tablets (specification: 20 mg/tablet) in healthy Chinese male subjects; 2) To evaluate the taste (palatability) of the subjects after taking the test preparation GP681 dry suspension.

Start Date12 Dec 2024

Sponsor / Collaborator

Jiangxi Kerui Pharmaceutical Co., Ltd

[+1]

CTR20243107

/ RecruitingPhase 3

GP681片用于成人及青少年流感暴露后预防的有效性及安全性的多中心、随机、双盲、安慰剂对照的Ⅲ期临床研究

[Translation] A multicenter, randomized, double-blind, placebo-controlled phase III clinical study on the efficacy and safety of GP681 tablets for post-exposure prevention of influenza in adults and adolescents

主要研究目的：评价口服单剂量的GP681片与安慰剂相比在流感患者（指示病例）的家庭成员（家庭接触者）流感暴露后预防的有效性。次要研究目的： 1）通过其他次要终点指标评估口服单剂量的GP681片与安慰剂相比在家庭接触者流感暴露后预防的有效性； 2）评价口服单剂量的GP681片与安慰剂相比在家庭接触者流感暴露后预防的安全性。

[Translation]

Main study objectives: To evaluate the effectiveness of a single oral dose of GP681 tablets compared with placebo in the prevention of influenza exposure in family members (household contacts) of influenza patients (index cases). Secondary study objectives: 1) To evaluate the effectiveness of a single oral dose of GP681 tablets compared with placebo in the prevention of influenza exposure in household contacts through other secondary endpoints; 2) To evaluate the safety of a single oral dose of GP681 tablets compared with placebo in the prevention of influenza exposure in household contacts.

Start Date01 Dec 2024

Sponsor / Collaborator

Jiangxi Kerui Pharmaceutical Co., Ltd

[+1]

100 Clinical Results associated with PA protein

100 Translational Medicine associated with PA protein

0 Patents (Medical) associated with PA protein

Literatures (Medical) associated with PA protein

22 Oct 2024·Journal of Virology

Two amino acid residues in the N-terminal region of the polymerase acidic protein determine the virulence of Eurasian avian-like H1N1 swine influenza viruses in mice

Article

Author: Xu, Chengzhi ; Yang, Huanliang ; Chen, Yan ; Qiao, Chuanling ; Zhang, Naixin ; Chen, Hualan ; Wu, Yunpu ; Liu, Liling ; Wan, Yunfei ; Meng, Fei ; Yang, Yuying

ABSTRACT Reassortant Eurasian avian-like H1N1 (rEA H1N1) viruses carrying the internal genes of H1N1/2009 virus have been circulating in pigs for more than 10 years and have caused sporadic human infections. The enhanced virulence phenotype of the rEA H1N1 viruses highlights potential risks to public health. However, the molecular mechanism underlying the viral pathogenicity of the currently circulating rEA H1N1 viruses remains unclear. In this study, we found that two naturally isolated rEA H1N1 swine influenza viruses, A/swine/Liaoning/FX38/2017 (FX38) and A/swine/Liaoning/SY72/2018 (SY72), possessed similar genetic characteristics but exhibited significantly different pathogenicity in a mouse model. Using reverse genetics, we demonstrated that amino acid mutations at positions 100 and 122 in the polymerase acidic (PA) protein had individual and synergistic effects on the polymerase activity and viral replication capacity in vitro , as well as the viral pathogenicity in mice. Furthermore, we revealed that amino acid residue 100 in PA influenced the transcription of viral RNA (vRNA) by altering the endonuclease activity, and amino acid residue 122 affected the synthesis of complementary RNA and messenger RNA by altering the RNA-binding ability and endonuclease activity of the PA protein. Taken together, we identified that two naturally occurring amino acid mutations in PA derived from H1N1/2009 virus are crucial determinants of the virulence of rEA H1N1 viruses and revealed the differential mechanism by which these two mutations affect the transcription and replication of vRNA. These findings will extend our understanding of the roles of PA in the virulence of influenza A viruses. IMPORTANCEMultiple genetic determinants are involved in the virulence of influenza A viruses. In this study, we identified two naturally occurring amino acid mutations, located at residues 100 and 122 in the polymerase acidic (PA) protein, which are associated with viral polymerase activity, replication competence, and pathogenicity in mice. In particular, we clarified the specific mechanism by which the two residues play an important role in viral transcription and replication. These findings will help to improve understanding the functions of amino acid residues in the N-terminal region of the PA protein involved in the pathogenicity of influenza A viruses.

01 Jul 2024·Virus Research

Exploration of influenza A virus PA protein-associated cellular proteins discloses its impact on mitochondrial function

Article

Author: Tam, Ee-Hong ; Lin, Yi-Ru ; Lin, Syh-Jae ; Ke, Po-Yuan ; Kuo, Rei-Lin ; Hsueh, Pei-Chun ; Shih, Yu-Yin ; Wang, Li-Ting ; Woung, Chian-Huey ; Tsai, Jia-Chen ; Wu, Chih-Ching ; Shen, Hsiang-Yi ; Chang, Chuang-Rung

Influenza A virus can infect respiratory tracts and may cause severe illness in humans. Proteins encoded by influenza A virus can interact with cellular factors and dysregulate host biological processes to support viral replication and cause pathogenicity. The influenza viral PA protein is not only a subunit of influenza viral polymerase but also a virulence factor involved in pathogenicity during infection. To explore the role of the influenza virus PA protein in regulating host biological processes, we performed immunoprecipitation and LC‒MS/MS to globally identify cellular factors that interact with the PA proteins of the influenza A H1N1, 2009 pandemic H1N1, and H3N2 viruses. The results demonstrated that proteins located in the mitochondrion, proteasome, and nucleus are associated with the PA protein. We further discovered that the PA protein is partly located in mitochondria by immunofluorescence and mitochondrial fractionation and that overexpression of the PA protein reduces mitochondrial respiration. In addition, our results revealed the interaction between PA and the mitochondrial matrix protein PYCR2 and the antiviral role of PYCR2 during influenza A virus replication. Moreover, we found that the PA protein could also trigger autophagy and disrupt mitochondrial homeostasis. Overall, our research revealed the impacts of the influenza A virus PA protein on mitochondrial function and autophagy.

01 Jun 2024·Advanced Healthcare Materials

Intranasal Epitope‐Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus

Article

Author: Kabir, Md. Tanvir ; Rehm, Bernd H. A. ; Wakim, Linda M. ; Zhang, Heran ; Liu, Ziyang ; Chen, Shuxiong

AbstractIntranasal vaccines, unlike injectable vaccines, boost immunity along the respiratory tract; this can significantly limit respiratory virus replication and shedding. There remains a need to develop mucosal adjuvants and vaccine delivery systems that are both safe and effective following intranasal administration. Here, biopolymer particles (BP) densely coated with repeats of MHC class I restricted immunodominant epitopes derived from influenza A virus namely NP366, a nucleoprotein‐derived epitope and PA224, a polymerase acidic subunit derived epitope, are bioengineered. These BP‐NP366/PA224 can be manufactured at a high yield and are obtained at ≈93% purity, exhibiting ambient‐temperature stability. Immunological characterization includes comparing systemic and mucosal immune responses mounted following intramuscular or intranasal immunization. Immunization with BP‐NP366/PA224 without adjuvant triggers influenza‐specific CD8+ T cell priming and memory CD8+ T cell development. Co‐delivery with the adjuvant poly(I:C) significantly boosts the size and functionality of the influenza‐specific pulmonary resident memory CD8+ T cell pool. Intranasal, but not intramuscular delivery of BP‐NP366/PA224 with poly(I:C), provides protection against influenza virus challenge. Overall, the BP approach demonstrates as a suitable antigen formulation for intranasal delivery toward induction of systemic protective T cell responses against influenza virus.

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PA protein

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