A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Trial of ZX-7101A Tablets to Evaluate the Efficacy and Safety in the Treatment of Uncomplicated Influenza in Adolescents

The primary object of this study is evaluating the efficacy of ZX-7101A tablets versus placebo in the treatment of uncomplicated simple influenza in adolescents.
The seongdary object is evaluating the safety of ZX-7101A tablet in the treatment of uncomplicated simple influenza in adolescents.

开始日期2023-10-25

申办/合作机构

Nanjing Zenshine Pharmaceuticals Co. Ltd.

CTR20232328 / Completed临床1期

一项单中心、开放、六序列、三周期、三交叉研究评估在中国成年健康受试者中 ZX-7101A 片和磷酸奥司他韦胶囊的药物-药物相互作用

主要目的：（1）在中国成年健康受试者中评估多次口服磷酸奥司他韦胶囊对单次口服 ZX-7101A 片后其活性代谢产物 ZX-7101 的药代动力学特征的影响；（2）在中国成年健康受试者中评估单次口服 ZX-7101A 片对多次口服磷酸奥司他韦胶囊后其前体药物奥司他韦和活性代谢产物奥司他韦羧酸盐的药代动力学特征的影响。次要目的：（1）在中国成年健康受试者中评估联合或不联合多次口服磷酸奥司他韦胶囊情况下，单次口服 ZX-7101A 片的安全性与耐受性；（2）在中国成年健康受试者中观察联合或不联合单次口服 ZX-7101A 片情况下，多次口服磷酸奥司他韦胶囊的安全性与耐受性；（3）在中国成年健康受试者中评估多次口服磷酸奥司他韦胶囊对单次口服 ZX-7101A 片后其前体药物 ZX-7101A 的药代动力学特征的影响。

开始日期2023-09-07

申办/合作机构

南京征祥医药有限公司

100 项与 PA protein x RdRp 相关的临床结果

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100 项与 PA protein x RdRp 相关的转化医学

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0 项与 PA protein x RdRp 相关的专利（医药）

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项与 PA protein x RdRp 相关的文献（医药）

2021-06-11·ACS Infectious Diseases2区 · 医学

Inhibition of Influenza Virus Polymerase by Interfering with Its Protein–Protein Interactions

2区 · 医学

Review

作者: Tabarrini, Oriana ; Nizi, Maria Giulia ; Desantis, Jenny ; Massari, Serena ; Cecchetti, Violetta

Influenza (flu) virus is a serious threat to global health with the potential to generate devastating pandemics. The availability of broad spectrum antiviral drugs is an unequaled weapon during pandemic events, especially when a vaccine is still not available. One of the most promising targets for the development of new antiflu therapeutics is the viral RNA-dependent RNA polymerase (RdRP). The assembly of the flu RdRP heterotrimeric complex from the individual polymerase acidic protein (PA), polymerase basic protein 1 (PB1), and polymerase basic protein 2 (PB2) subunits is a prerequisite for RdRP functions, such as mRNA synthesis and genome replication. In this Review, we report the known protein-protein interactions (PPIs) occurring by RdRP that could be disrupted by small molecules and analyze their benefits and drawbacks as drug targets. An overview of small molecules able to interfere with flu RdRP functions exploiting the PPI inhibition approach is described. In particular, an update on the most recent inhibitors targeting the well-consolidated RdRP PA-PB1 subunit heterodimerization is mainly reported, together with pioneer inhibitors targeting other virus-virus or virus-host interactions involving RdRP subunits. As demonstrated by the PA-PB1 interaction inhibitors discussed herein, the inhibition of flu RdRP functions by PPI disrupters clearly represents a valid means to identify compounds endowed with a broad spectrum of action and a reduced propensity to develop drug resistance, which are the main issues of antiviral drugs.

2020-11-01·Cell Reports1区 · 生物学

Type-IInterferon-Inducible SERTAD3 Inhibits Influenza A Virus Replication by Blocking the Assembly of Viral RNA Polymerase Complex

1区 · 生物学

ArticleOA

作者: Peishuang Du ; Yong-Qiang Deng ; Genhong Cheng ; Xiang Chen ; Tao Jiang ; Xiao-Feng Li ; Chunfeng Li ; Cheng-Feng Qin ; Nina Sun ; Lili Li ; Ping Liu ; Sarah Gold ; Shulong Zu ; Na-Na Zhang ; Ning Lu ; Rong-Rong Zhang ; Jingfeng Wang

Influenza A virus (IAV) infection stimulates a type I interferon (IFN-I) response in host cells that exerts antiviral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). However, most ISGs are poorly studied for their roles in the infection of IAV. Herein, we demonstrate that SERTA domain containing 3 (SERTAD3) has a significant inhibitory effect on IAV replication in vitro. More importantly, Sertad3^-/- mice develop more severe symptoms upon IAV infection. Mechanistically, we find SERTAD3 reduces IAV replication through interacting with viral polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), and polymerase acidic protein (PA) to disrupt the formation of the RNA-dependent RNA polymerase (RdRp) complex. We further identify an 8-amino-acid peptide of SERTAD3 as a minimum interacting motif that can disrupt RdRp complex formation and inhibit IAV replication. Thus, our studies not only identify SERTAD3 as an antiviral ISG, but also provide the mechanism of potential application of SERTAD3-derived peptide in suppressing influenza replication.

Pharmaceutics

Exploring a New Generation of Pyrimidine and Pyridine Derivatives as Anti-Influenza Agents Targeting the Polymerase PA–PB1 Subunits Interaction

Article

作者: Bertagnin, Chiara ; Mori, Mattia ; Giacchello, Ilaria ; Cianciusi, Annarita ; Schenone, Silvia ; Musumeci, Francesca ; Bonomini, Anna ; Carbone, Anna ; Loregian, Arianna ; Francesconi, Valeria

The limited range of available flu treatments due to virus mutations and drug resistance have prompted the search for new therapies. RNA-dependent RNA polymerase (RdRp) is a heterotrimeric complex of three subunits, i.e., polymerase acidic protein (PA) and polymerase basic proteins 1 and 2 (PB1 and PB2). It is widely recognized as one of the most promising anti-flu targets because of its critical role in influenza infection and high amino acid conservation. In particular, the disruption of RdRp complex assembly through protein–protein interaction (PPI) inhibition has emerged as a valuable strategy for discovering a new therapy. Our group previously identified the 3-cyano-4,6-diphenyl-pyridine core as a privileged scaffold for developing PA–PB1 PPI inhibitors. Encouraged by these findings, we synthesized a small library of pyridine and pyrimidine derivatives decorated with a thio-N-(m-tolyl)acetamide side chain (compounds 2a–n) or several amino acid groups (compounds 3a–n) at the C2 position. Interestingly, derivative 2d, characterized by a pyrimidine core and a phenyl and 4-chloro phenyl ring at the C4 and C6 positions, respectively, showed an IC50 value of 90.1 μM in PA–PB1 ELISA, an EC50 value of 2.8 μM in PRA, and a favorable cytotoxic profile, emerging as a significant breakthrough in the pursuit of new PPI inhibitors. A molecular modeling study was also completed as part of this project, allowing us to clarify the biological profile of these compounds.