Interferon alpha-2

干扰素 α - 2
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  • 文章类型: Journal Article
    有限的数据已经报道了使用聚乙二醇干扰素(PEG-IFN)α-2b治疗产后乙型肝炎e抗原(HBeAg)阴性女性慢性乙型肝炎病毒(HBV)感染。这项研究是评估PEG-IFNα-2b在HBV产后妇女无HBeAg的有效性和安全性,并确定与功能治愈相关的因素。
    共有150例HBeAg阴性产后妇女回顾性招募。47例患者接受PEG-IFNα-2b[PEG-IFN(+)组]和103例患者没有[PEG-IFN(-)组]。采用倾向评分匹配法(PSM)调整两组基线失衡。随访患者至少48周。主要终点是48周时的乙型肝炎表面抗原(HBsAg)丢失和HBsAg血清转换。采用Logistic回归分析评估48周时HBsAg消失的相关因素。
    在第48周时,Peg-IFN(+)组的HBsAg消失和血清转换率分别为51.06%(24/47)和40.43%(19/47),分别。即使在PSM之后,PEG-IFN(+)组仍显示较高的HBsAg损失率(50.00%vs7.14%,p<0.001)和更高的HBsAg血清转换率(38.10%vs2.38%,p<0.001)。基线HBsAg水平(赔率比[OR]:0.051,95%置信区间[CI]:0.003-0.273,P=0.010),HBsAg在第24周(OR:0.214,95CI:0.033-0.616,P=0.022),第24周HBsAg下降(OR:4.682,95CI:1.624-30.198,P=0.022)和产后耀斑(OR:21.181,95CI:1.872-633.801,P=0.030)与PEG-IFNα-2b治疗后第48周的HBsAg消失显着相关。此外,受试者工作特征曲线(ROC)显示,使用基线HBsAg<182IU/mL,HBsAg在第24周<4IU/mL和HBsAg下降在第24周>12IU/mL是HBsAg消失的良好预测因子。未报告严重不良事件。
    PEG-IFNα-2b治疗可以实现HBsAg丢失和HBeAg阴性产后妇女血清转换的高比率,具有可靠的安全性,特别是对于经历产后耀斑和基线HBsAg水平低的患者。
    UNASSIGNED: Limited data have been reported on achieving functional cure using pegylated interferon (Peg-IFN) alpha-2b treatment for postpartum hepatitis B e antigen (HBeAg)-negative women with chronic hepatitis B virus (HBV) infection. This study was to assess the effectiveness and safety of Peg-IFN alpha-2b in HBV postpartum women without HBeAg and identify factors linked to the functional cure.
    UNASSIGNED: A total of 150 HBeAg-negative postpartum women were retrospectively recruited.47 patients received Peg-IFN alpha-2b [Peg-IFN(+) group] and 103 patients did not [Peg-IFN(-) group]. Propensity score matching (PSM) was used to adjust the baseline imbalance between the two groups. The patients were followed for at least 48 weeks. The primary endpoints were hepatitis B surface antigen(HBsAg) loss and HBsAg seroconversion at 48 weeks. Logistic regression analysis was used to assess factors associated with HBsAg loss at 48 weeks.
    UNASSIGNED: At week 48,the HBsAg loss and seroconversion rate in Peg-IFN(+) group were 51.06%(24/47) and 40.43%(19/47), respectively. Even after PSM, Peg-IFN(+) group still showed higher HBsAg loss rate (50.00% vs 7.14%,p<0.001) and higher HBsAg seroconversion rate (38.10% vs 2.38%,p<0.001). Baseline HBsAg levels (Odds Ratio [OR]: 0.051, 95% Confidence Interval [CI]: 0.003-0.273, P=0.010), HBsAg at week 24 (OR:0.214, 95%CI:0.033-0.616, P=0.022), HBsAg decline at week 24 (OR:4.682, 95%CI: 1.624-30.198, P=0.022) and postpartum flare (OR:21.181, 95%CI:1.872-633.801, P=0.030) were significantly associated with HBsAg loss at week 48 after Peg-IFN alpha-2b therapy. Furthermore, the receiver operating characteristic curve (ROC) showed that the use of baseline HBsAg<182 IU/mL, HBsAg at week24 < 4 IU/mL and HBsAg decline at week24>12IU/mL were good predictors of HBsAg loss. No serious adverse events were reported.
    UNASSIGNED: Peg-IFN alpha-2b treatment could achieve a high rate of HBsAg loss and seroconversion in HBeAg-negative postpartum women with reliable safety, particularly for patients experience postpartum flare and have low baseline HBsAg levels.
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  • 文章类型: Journal Article
    目的:关于替诺福韦艾拉酚胺(TAF)加聚乙二醇干扰素-α(Peg-IFN-α)在慢性乙型肝炎(CHB)儿童中的安全性和有效性的数据缺乏。目前的研究旨在呈现谁通过使用TAF和PEG-IFN-α获得功能性治愈的四个儿科CHB患者的特征。
    方法:在2019年5月开始的病例系列研究中,10名没有临床症状或体征的儿童接受了应答指导(HBVDNA检测不到,乙型肝炎e抗原[HBeAg]丢失或血清转换,和乙型肝炎表面抗原[HBsAg]损失或血清转换)和功能性治愈靶向(HBsAg损失或血清转换)TAF(25毫克/天,口服)加PEG-IFN-α-2b(180µg/1.73m2,皮下,每周一次)联合(9/10)或序贯(1/10)治疗。监测这些治疗的安全性和有效性。
    结果:截至2024年4月,在平均31.5个月的治疗后,十分之四的儿童获得了功能性治愈,其他六个孩子仍在接受治疗。这四个治愈的孩子,2岁、4岁、8岁和6岁,均为HBeAg阳性,丙氨酸转氨酶水平为80,47,114和40U/L;HBVDNA水平为71200000,93000000,8220和96700000IU/mL;HBsAg水平为39442.8,15431.2,22和33013.1IU/mL,分别。治疗期间,所有儿童(10/10)都经历了轻度或中度不良事件,包括流感样症状,厌食症,疲劳,和血细胞减少症。值得注意的是,生长迟缓(8/10)是最显著的不良事件;在接受联合治疗的3名治愈儿童(3/4)中发生,在接受序贯治疗的另1名治愈儿童(1/4)中出现的程度较低.幸运的是,所有3名治愈儿童在治疗后9个月恢复或超过正常生长水平.
    结论:TAF加PEG-IFN-α-2b治疗是潜在的安全和有效的儿科CHB患者,这可能为未来的临床实践和针对CHB儿童功能性治疗的研究设计提供重要的见解。
    OBJECTIVE: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α.
    METHODS: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored.
    RESULTS: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment.
    CONCLUSIONS: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.
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  • 文章类型: Journal Article
    原发性骨髓纤维化(PMF)是骨髓增殖性肿瘤中最具侵袭性的,患者需要更多的关注,可能需要更早的治疗干预。目前批准的治疗选择在选择性抑制由驱动和共存基因突变导致的克隆增殖方面受到限制。Janus激酶抑制剂被批准用于有症状的高危PMF患者。此外,大多数正在进行的临床研究集中在高危疾病和/或输血依赖率高的患者.早期/低风险PMF的最佳治疗仍有待确定,需要随机临床试验评估。根据2期非随机研究和专家意见,建议将聚乙二醇化干扰素α用于有症状的低风险PMF患者。Ropeg干扰素alfa-2b(ropeg)是新一代聚乙二醇化干扰素为基础的治疗具有良好的药代动力学和安全性,需要比以前的配方更少的频繁注射。这个随机的,双盲,安慰剂对照3期试验将评估其在“早期/低危PMF”患者中的疗效和安全性,根据动态国际预后评分系统+,定义为纤维化前PMF或低或中1风险的PMF。共同主要终点包括临床相关的完全血液学反应和症状终点。次要终点包括进展或无事件生存,驱动或相关共存基因突变的分子反应,骨髓反应,和安全。疾病进展和事件的定义基于国际工作组标准和广泛发表的报告。150名符合条件的患者将以2:1的比例随机分配,以接受ropeg或安慰剂。盲样本量重新估计设计Ropeg将皮下给药,较高的起始剂量方案。该研究将为早期/低风险PMF的治疗提供重要数据,疾病调节剂是非常需要的。
    Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with \"early/lower-risk PMF\", defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed.
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  • 文章类型: Journal Article
    在过去十年中,真性红细胞增多症(PV)的治疗前景取得了重大进展,包括在羟基脲之后的二线设置中批准了鲁索替尼,聚乙二醇干扰素-α2b,以及一类名为hepcidin模拟物的新型药物的高级临床开发。
    我们对讨论风险分层的证据进行了全面审查,治疗适应症,仅放血方法和关键试验的作用和局限性,涵盖与使用干扰素-α(IFN-α)有关的细微差别,鲁索替尼,铁调素模拟物和即将到来的研究药物,包括HDAC和LSD1抑制剂。
    PV的研究范式正在缓慢地从对血细胞比容控制的唯一关注转向疾病改变。铁调素模拟物的发现是恢复铁稳态的突破,实现静脉切开术的独立性,并可能导致更严格的血细胞比容控制改善无血栓生存率。另一方面,新出现的IFN-α和鲁索替尼以及两种药物的联合使用数据表明,在部分PV患者中实现分子缓解的潜力,等待长期随访,以验证分子反应与无进展和无血栓形成生存期的临床相关结局之间的相关性.
    UNASSIGNED: The treatment landscape of polycythemia vera (PV) has seen major advancements within the last decade including approval of ruxolitinib in the second line setting after hydroxyurea, ropegylated interferon-α2b, and advanced clinical development of a novel class of agents called hepcidin mimetics.
    UNASSIGNED: We provide a comprehensive review of the evidence discussing the risk stratification, treatment indications, role and limitations of phlebotomy only approach and pivotal trials covering nuances related to the use of interferon-α (IFN-α), ruxolitinib, hepcidin mimetics, and upcoming investigational agents including HDAC and LSD1 inhibitors.
    UNASSIGNED: The research paradigm in PV is slowly shifting from the sole focus on hematocrit control and moving toward disease modification. The discovery of hepcidin mimetics has come as a breakthrough in restoring iron homeostasis, achieving phlebotomy-independence and may lead to improved thrombosis-free survival with stricter hematocrit control. On the other hand, emerging data with IFN- α and ruxolitinib as well as combination of the two agents suggests the potential for achieving molecular remission in a subset of PV patients and long-term follow-up is awaited to validate the correlation of molecular responses with clinically relevant outcomes of progression-free and thrombosis-free survival.
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  • 文章类型: Journal Article
    目的:外生性鼻窦乳头状瘤(ESP)是一种鼻腔鼻窦良性肿瘤。通过内窥镜手术进行完整的手术切除是首选治疗方法。然而,高复发率(5年随访36%)与此方法有关,这可能表明存在微生物,例如人乳头瘤病毒(HPV)。重要的是要注意,ESP的标准治疗不包括抗病毒药物。在我们的研究中,我们正在测试含干扰素的药物在减少ESP患者复发和术后反应方面的有效性.
    方法:我们纳入了78例患者,年龄在23-83岁之间,通过鼻内镜和鼻内镜检查确诊为ESP,并且在鼻刮片中HPVPCR检测阳性。为了比较结果,我们将患者分为主组和对照组。主组术后接受重组人干扰素,而对照组没有接受药物治疗。我们进行了统计分析,以比较在术后不同阶段无反应表现的患者比例,以及比较某些观察阶段复发性ESP患者的比例。
    结果:重组人干扰素的引入加速了术后反应的消退,并促进了手术切除ESP后鼻粘膜的愈合。我们还发现重组干扰素治疗与ESP复发率降低之间存在统计学上的显着关联。
    结论:根据研究结果,发现在术后接受rhIFN-α2b(重组人干扰素α2b)的主要患者组中,与未服用该药物的对照组患者相比,ESP的复发频率和术后恢复时间显着降低。
    方法:队列研究。
    OBJECTIVE: Exophytic Sinonasal Papilloma (ESP) is a benign tumor of the sinonasal tract. Complete surgical excision by endoscopic surgery is the treatment of choice. However, a high recurrence rate (36% at 5-year follow-up) is associated with this method, which may indicate the presence of microorganisms such as Human Papillomavirus (HPV). It is important to note that the standard treatment for ESP does not include antiviral drugs. In our study, we are testing the effectiveness of an interferon-containing drug in reducing recurrence and postoperative reactions in patients with ESP.
    METHODS: We included 78 patients aged 23-83 years with a confirmed diagnosis of ESP by rhinoscopy and nasal endoscopy and a positive PCR test for HPV in nasal scrapings. To compare the results, we divided the patients into main and control groups. The main group received recombinant human interferon after surgery, while the control group did not receive the drug. We performed a statistical analysis to compare the proportion of patients without reactive manifestations at different stages of the postoperative period, as well as to compare the proportion of patients with recurrent ESP at certain stages of observation.
    RESULTS: The introduction of recombinant human interferon accelerated the resolution of postoperative reactions and promoted the healing of the nasal mucosa after surgical removal of the ESP. We also found a statistically significant association between treatment with recombinant interferon and a reduction in the recurrence rate of ESP.
    CONCLUSIONS: According to the results of the study, it was found that in the main group of patients who received rhIFN-α2b (recombinant human Interferon alpha 2b) in the postoperative period, the frequency of relapses of ESP and the time of postoperative recovery were significantly lower than in patients in the control group who did not take the drug.
    METHODS: Cohort Study.
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  • 文章类型: Journal Article
    真性红细胞增多症(PV)是费城染色体阴性的骨髓增殖性肿瘤,其特征是克隆性红细胞增多症。一项2期研究报道,在日本患者中,对PV具有良好的耐受性和有效的治疗方法。对2期数据的事后分析进一步评估了低血栓形成风险(低风险PV)患者的预后。在20例低风险PV患者中,到第24周和第52周,分别有60.0%(12/20)和85.0%(17/20)的血细胞比容<45%。在第52周,具有完全血液学反应(CHR)的响应者比例为60.0%(12/20),中位反应时间为11.9个月。平均JAK2V617F等位基因负荷从基线时的75.8%下降到第52周的53.7%。没有患者经历血栓形成或出血事件。所有患者都经历了与索普干扰素α-2b相关的治疗紧急不良事件(TEAE),但没有发生≥3级TEAE或与α-2b相关的死亡,并没有出现新的安全问题。该分析表明,对于日本低危PV患者,索普干扰素α-2b可能是一种有效的治疗选择。
    Polycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by clonal erythrocytosis. A phase 2 study reported that ropeginterferon alfa-2b is a well-tolerated and effective treatment for PV in Japanese patients. This post hoc analysis of the phase 2 data further evaluated outcomes in patients at low risk of thrombosis (low-risk PV). Among 20 patients with low-risk PV, 60.0% (12/20) and 85.0% (17/20) achieved < 45% hematocrit by weeks 24 and 52, respectively. The proportion of responders with complete hematologic response (CHR) was 60.0% (12/20) at week 52, and the median time to response was 11.9 months. The mean JAK2 V617F allele burden decreased from 75.8% at baseline to 53.7% at week 52. No patient experienced thrombosis or bleeding episodes. All patients experienced treatment-emergent adverse events (TEAEs) related to ropeginterferon alfa-2b, but no grade ≥ 3 TEAEs or deaths related to ropeginterferon alfa-2b occurred, and no new safety concerns arose. This analysis indicated that ropeginterferon alfa-2b may be an effective treatment option for Japanese patients with low-risk PV.
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  • 文章类型: Journal Article
    单纯疱疹病毒1型(HSV-1)和2型(HSV-2)是广泛存在的人类病原体,其建立导致反复发作的慢性潜伏感染。目前的治疗方法有限,需要开发新的抗病毒策略。本研究旨在评估含有干扰素α-2b(IFNα-2b)的新型局部制剂对HSV-1和HSV-2的抗病毒功效。配方,Oftalmoferon®forte(滴眼液)和干扰素阴道片,在Vero细胞中证明了对HSV-1和HSV-2的有效抗病毒作用,分别,与病毒复制的浓度依赖性抑制。随后,在动物模型中测试了它们的功效:兔眼模型中的HSV-1角膜炎和小鼠中的HSV-2生殖器疱疹。Oftalmoferon®forte有效治疗HSV-1角膜炎,与病毒控制相比,减少临床症状和溃疡。干扰素阴道片在控制小鼠HSV-2生殖器疱疹方面显示出有希望的结果,提高生存率,减少临床症状,体重减轻和病毒复制。新型IFNα-2b制剂在细胞培养物和动物模型中表现出针对HSV感染的显著抗病毒活性。这些发现表明这些制剂作为HSV感染的替代疗法的潜力。特别是在对当前疗法有抵抗力的情况下。需要进一步的研究来优化治疗方案并评估人类的临床疗效。
    Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.
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  • 文章类型: Journal Article
    人干扰素α2(IFNα2)是一种具有广谱抗病毒活性的细胞因子,其工程形式广泛用于治疗病毒感染。然而,IFNα2可能在治疗期间引发促炎反应和潜在的副作用。三叶因子2(TFF2)是一种具有抗炎特性的分泌蛋白。这里,我们探讨了以二合一融合形式偶联IFNα2与TFF2是否可以将两种分子对病毒感染的有益作用结合起来,从而获得更理想的治疗结果.我们设计了两种形式的人IFNα2和TFF2融合蛋白,IFNα2-TFF2-Fc(ITF)和TFF2-IFNα2-Fc(TIF),并与单独的IFNα2和TFF2相比,在体外检查了它们的特性。RNA-Seq被进一步用于探索在跨切片水平的动态基因调控上的这种比较。这些体外评估共同表明,TIF在很大程度上保留了IFNα2的抗病毒活性,同时是一个较弱的炎症诱导剂,与TFF2活性的存在一致。我们进一步证明了TIF在使用小鼠感染模型治疗流感感染方面优于单独的IFNα2或TFF2。一起,我们的研究提供了证据支持,通过具有IFNα2赋予的抗病毒活性与TFF2的互补在抑制炎症副作用,融合蛋白,特别是TIF,代表比单独的IFNα2或TFF2更有效的抗流感和其他呼吸道病毒感染的药物。这意味着合并具有互补功能的两个分子具有开发针对病毒感染的新型疗法的潜力。
    Human interferon α2 (IFNα2) is a cytokine with broad-spectrum antiviral activity, and its engineered forms are widely used to treat viral infections. However, IFNα2 may trigger proinflammatory responses and underlying side effects during treatment. Trefoil factor 2 (TFF2) is a secreted protein with anti-inflammatory properties. Here, we explored whether coupling IFNα2 to TFF2 in a two-in-one fusion form could combine the beneficial effects of both molecules on viral infections toward a more desirable treatment outcome. We engineered two forms of human IFNα2 and TFF2 fusion proteins, IFNα2-TFF2-Fc (ITF) and TFF2-IFNα2-Fc (TIF), and examined their properties in vitro in comparison to IFNα2 and TFF2 alone. RNA-Seq was further used to explore such comparison on dynamic gene regulation at transriptomic level. These in vitro assessments collectively indicated that TIF largely retained the antiviral activity of IFNα2 while being a weaker inflammation inducer, consistent with the presence of TFF2 activity. We further demonstrated the superiority of TIF over IFNα2 or TFF2 alone in treating influenza infection using a mouse infection model. Together, our study provided evidence supporting that, by possessing antiviral activity conferred by IFNα2 with complementation from TFF2 in suppressing the inflammatory side effects, the fusion proteins, particularly TIF, represent more effective agents against influenza and other respiratory viral infections than IFNα2 or TFF2 alone. It implies that merging two molecules with complementary functions holds potential for developing novel therapeutics against viral infections.
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