Pub Date : 2026-03-01Epub Date: 2026-01-24DOI: 10.1016/j.antiviral.2026.106357
Yuanmei Zhu , Huihui Chong , Nian Liu, Yuxian He
Lipovirtide, also known as LP-80, is a lipopeptide-based HIV fusion inhibitor with potent broad-spectrum and long-lasting antiviral activity. We recently reported the pharmacokinetics and safety of Lipovirtide in rats (Zhu et al. 2025); herein, its pharmacokinetics and safety profiles in cynomolgus macaques were systematically evaluated. Lipovirtide was rapidly absorbed after subcutaneous administration, with absolute bioavailability (F) of 110.11 % in male and 92.33 % in female. The time to reach maximum plasma concentration (Tmax) ranged from 4 to 8 h, and the terminal half-life (T1/2) was between 10.18 and 13.51 h. Comprehensive safety assessments revealed no significant effects on cardiovascular or respiratory functions in conscious macaques after a single subcutaneous administration. General toxicity studies demonstrated its excellent tolerability, with a maximum tolerated dose above 150 mg/kg for single dosing; the 4-week and 39-week repeated dosing determined the no-observed-adverse-effect level (NOAEL) to be 15 mg/kg. Toxicokinetic analyses confirmed that long-term administration did not lead to drug accumulation in both male and female animals. No anti-drug antibody (ADA) formation was observed throughout the study schedule. Collectively, our preclinical characterizations provide compelling data to support the clinical development of Lipovirtide, which has already progressed to a phase III clinical trial.
脂virtide，也称为LP-80，是一种基于脂肽的HIV融合抑制剂，具有广谱和长效抗病毒活性。我们最近报道了Lipovirtide在大鼠体内的药代动力学和安全性（Zhu et al. 2025）；本文对其在食蟹猕猴体内的药代动力学和安全性进行了系统评价。脂维肽皮下给药后吸收迅速，男性绝对生物利用度(F)为110.11%，女性为92.33%。达到最大血药浓度（Tmax）的时间为4 ~ 8小时(h)，终末半衰期（T1/2）在10.18 ~ 13.51小时之间。综合安全性评估显示，单次皮下给药对有意识猕猴的心血管或呼吸功能无显著影响。一般毒性研究表明其良好的耐受性，单次给药的最大耐受剂量超过150 mg/kg；4周和39周的重复给药确定无观察到的不良反应水平（NOAEL）为15 mg/kg。毒代动力学分析证实，长期给药不会导致雄性和雌性动物的药物积累。在整个研究过程中未观察到抗药物抗体（ADA）的形成。总的来说，我们的临床前特征提供了令人信服的数据来支持Lipovirtide的临床开发，该药物已经进入了III期临床试验。
{"title":"Pharmacokinetics and safety of HIV fusion inhibitor Lipovirtide in non-human primates","authors":"Yuanmei Zhu , Huihui Chong , Nian Liu, Yuxian He","doi":"10.1016/j.antiviral.2026.106357","DOIUrl":"10.1016/j.antiviral.2026.106357","url":null,"abstract":"<div><div>Lipovirtide, also known as LP-80, is a lipopeptide-based HIV fusion inhibitor with potent broad-spectrum and long-lasting antiviral activity. We recently reported the pharmacokinetics and safety of Lipovirtide in rats (Zhu et al. 2025); herein, its pharmacokinetics and safety profiles in cynomolgus macaques were systematically evaluated. Lipovirtide was rapidly absorbed after subcutaneous administration, with absolute bioavailability (F) of 110.11 % in male and 92.33 % in female. The time to reach maximum plasma concentration (T<sub>max</sub>) ranged from 4 to 8 h, and the terminal half-life (T<sub>1/2</sub>) was between 10.18 and 13.51 h. Comprehensive safety assessments revealed no significant effects on cardiovascular or respiratory functions in conscious macaques after a single subcutaneous administration. General toxicity studies demonstrated its excellent tolerability, with a maximum tolerated dose above 150 mg/kg for single dosing; the 4-week and 39-week repeated dosing determined the no-observed-adverse-effect level (NOAEL) to be 15 mg/kg. Toxicokinetic analyses confirmed that long-term administration did not lead to drug accumulation in both male and female animals. No anti-drug antibody (ADA) formation was observed throughout the study schedule. Collectively, our preclinical characterizations provide compelling data to support the clinical development of Lipovirtide, which has already progressed to a phase III clinical trial.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106357"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-19DOI: 10.1016/j.antiviral.2026.106351
Charlotte Hedskog , Lauren Rodriguez , Yu Hu , Jiani Li , Dong Han , Nadine Peinovich , Clarissa Martinez , Pui Yan Ho , Jason K. Perry , Juan María González Del Castillo , Yiannis Koullias , Ross Martin , Robert H. Hyland
Obeldesivir is an oral nucleoside analog prodrug that targets and inhibits the SARS-CoV-2 RNA-dependent RNA polymerase Nsp12. This study evaluated the development of obeldesivir resistance in participants from the Phase 3, multicenter, double-blind BIRCH study. High-risk, nonhospitalized adults with COVID-19 were randomized to receive obeldesivir or placebo twice daily for 5 days. Mid-turbinate nasal swab samples were collected on Days 1 (baseline), 3, 5, 10, and 15. Amino acid substitutions were identified using deep sequencing and phenotyped using a replicon system. Of the 465 participants randomized and treated, 252 (obeldesivir, 190; placebo, 62) met the sequencing analysis criteria and had sequencing data at baseline. Phenotypic analysis of the 5 Nsp12 substitutions observed at baseline resulted in half-maximal effective concentration (EC50) fold changes ≤1.8 relative to the wildtype reference, indicating no change in susceptibility to obeldesivir. Among participants with baseline and postbaseline sequencing data, 12/73 (16.4 %) and 5/54 (9.3 %) participants in the obeldesivir and placebo groups, respectively, had emergent Nsp12 substitutions. Nine emergent Nsp12 substitutions were detected in the obeldesivir group postbaseline that were not observed in the placebo group. Of these, only 1 substitution (V792I) observed in 1 participant from the obeldesivir group demonstrated a low-level reduction in susceptibility to obeldesivir (EC50 fold change, 4.01). This substitution was first detected on Day 15, and the participant was never hospitalized. The low-to-no change in obeldesivir susceptibility among the treatment-emergent Nsp12 substitutions indicates a high barrier to the development of obeldesivir resistance in high-risk, nonhospitalized patients with COVID-19.
{"title":"SARS-CoV-2 resistance analyses from the Phase 3 BIRCH study of obeldesivir in high-risk nonhospitalized participants with COVID-19","authors":"Charlotte Hedskog , Lauren Rodriguez , Yu Hu , Jiani Li , Dong Han , Nadine Peinovich , Clarissa Martinez , Pui Yan Ho , Jason K. Perry , Juan María González Del Castillo , Yiannis Koullias , Ross Martin , Robert H. Hyland","doi":"10.1016/j.antiviral.2026.106351","DOIUrl":"10.1016/j.antiviral.2026.106351","url":null,"abstract":"<div><div>Obeldesivir is an oral nucleoside analog prodrug that targets and inhibits the SARS-CoV-2 RNA-dependent RNA polymerase Nsp12. This study evaluated the development of obeldesivir resistance in participants from the Phase 3, multicenter, double-blind BIRCH study. High-risk, nonhospitalized adults with COVID-19 were randomized to receive obeldesivir or placebo twice daily for 5 days. Mid-turbinate nasal swab samples were collected on Days 1 (baseline), 3, 5, 10, and 15. Amino acid substitutions were identified using deep sequencing and phenotyped using a replicon system. Of the 465 participants randomized and treated, 252 (obeldesivir, 190; placebo, 62) met the sequencing analysis criteria and had sequencing data at baseline. Phenotypic analysis of the 5 Nsp12 substitutions observed at baseline resulted in half-maximal effective concentration (EC<sub>50</sub>) fold changes ≤1.8 relative to the wildtype reference, indicating no change in susceptibility to obeldesivir. Among participants with baseline and postbaseline sequencing data, 12/73 (16.4 %) and 5/54 (9.3 %) participants in the obeldesivir and placebo groups, respectively, had emergent Nsp12 substitutions. Nine emergent Nsp12 substitutions were detected in the obeldesivir group postbaseline that were not observed in the placebo group. Of these, only 1 substitution (V792I) observed in 1 participant from the obeldesivir group demonstrated a low-level reduction in susceptibility to obeldesivir (EC<sub>50</sub> fold change, 4.01). This substitution was first detected on Day 15, and the participant was never hospitalized. The low-to-no change in obeldesivir susceptibility among the treatment-emergent Nsp12 substitutions indicates a high barrier to the development of obeldesivir resistance in high-risk, nonhospitalized patients with COVID-19.</div><div>Clinicaltrials.gov identifier: NCT05603143.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106351"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-03DOI: 10.1016/j.antiviral.2026.106360
Jean-Michel Pawlotsky
The advent of highly effective direct-acting antivirals (DAAs) has transformed hepatitis C virus (HCV) infection into a curable disease, with cure rates exceeding 95% across viral genotypes and clinical settings. Along with simplified, short-course treatment regimens and significant advancements in diagnostic technologies, these therapeutic breakthroughs have made eliminating HCV as a public health concern, as defined by the World Health Organization, a realistic goal. However, despite this progress, global advances toward elimination have fallen short of expectations. This review examines why HCV elimination appears to be within reach yet remains elusive. First, the molecular virology of HCV and the pharmacological rationale underlying modern DAA combination therapies are summarized to highlight how complementary antiviral mechanisms and high genetic barriers to resistance enable definitive virological cure. Then, the key factors limiting the translation of individual-level cures into population-level impact are analyzed. Persistent transmission in high-risk and marginalized populations, including people who inject drugs, incarcerated individuals, and men who have sex with men, continues to drive new infections. Incomplete case identification, losses along the care cascade, reinfection in the absence of protective immunity, and the lack of a prophylactic vaccine further constrain treatment-based prevention strategies. Structural and systemic barriers, including stigma, criminalization, inequitable access to diagnostics and treatment, fragile health systems, and uneven political commitment, exacerbate these challenges, particularly in low- and middle-income countries. Eliminating HCV will require sustained political commitment, equitable scaling up of testing and treatment, integration of care into primary and community-based services, robust harm reduction interventions, and coordination.
{"title":"Hepatitis C virus elimination: So close, so far?","authors":"Jean-Michel Pawlotsky","doi":"10.1016/j.antiviral.2026.106360","DOIUrl":"10.1016/j.antiviral.2026.106360","url":null,"abstract":"<div><div>The advent of highly effective direct-acting antivirals (DAAs) has transformed hepatitis C virus (HCV) infection into a curable disease, with cure rates exceeding 95% across viral genotypes and clinical settings. Along with simplified, short-course treatment regimens and significant advancements in diagnostic technologies, these therapeutic breakthroughs have made eliminating HCV as a public health concern, as defined by the World Health Organization, a realistic goal. However, despite this progress, global advances toward elimination have fallen short of expectations. This review examines why HCV elimination appears to be within reach yet remains elusive. First, the molecular virology of HCV and the pharmacological rationale underlying modern DAA combination therapies are summarized to highlight how complementary antiviral mechanisms and high genetic barriers to resistance enable definitive virological cure. Then, the key factors limiting the translation of individual-level cures into population-level impact are analyzed. Persistent transmission in high-risk and marginalized populations, including people who inject drugs, incarcerated individuals, and men who have sex with men, continues to drive new infections. Incomplete case identification, losses along the care cascade, reinfection in the absence of protective immunity, and the lack of a prophylactic vaccine further constrain treatment-based prevention strategies. Structural and systemic barriers, including stigma, criminalization, inequitable access to diagnostics and treatment, fragile health systems, and uneven political commitment, exacerbate these challenges, particularly in low- and middle-income countries. Eliminating HCV will require sustained political commitment, equitable scaling up of testing and treatment, integration of care into primary and community-based services, robust harm reduction interventions, and coordination.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106360"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-23DOI: 10.1016/j.antiviral.2026.106356
Dariya Begum, Teng Ai, Daniel J. Wilson, Liqiang Chen, Robert J. Geraghty
Human cytomegalovirus (HCMV) is a prevalent herpesvirus pathogen and remains a significant cause for mortality and morbidity in immunocompromised individuals and newborns. Like all viruses, HCMV uses host cellular proteins to facilitate virus replication and spread. Sirtuin 2 (SIRT2) is an NAD+-dependent deacetylase with a variety of substrates, including α-tubulin, where acetylation can alter function and stability. We have previously developed small molecule inhibitors targeting SIRT2 and in the current study, we show that two new compounds inhibit SIRT2 activity and also inhibit HCMV replication. The combination of these SIRT2 inhibitors with standard antivirals such as ganciclovir or letermovir resulted in a generally additive profile. Using indirect immunofluorescence, we determined that SIRT2 and SIRT1 expression was reduced over time in compound treated and untreated cells. We also observed SIRT2 and SIRT1 expression was increased in HCMV infected cells, compared to surrounding uninfected cells, regardless of compound treatment. GAPDH expression was stable over time and did not increase in HCMV infected cells, indicating a possible sirtuin-specific mechanism for upregulation of SIRT2 and 1 expression in infected cells. Further investigation is required to better understand the underlying anti-HCMV mechanism of action for our SIRT2 inhibitors and how HCMV infection impacts SIRT2 expression.
{"title":"Nicotinamide-based Sirtuin 2 inhibitors as anti-HCMV agents","authors":"Dariya Begum, Teng Ai, Daniel J. Wilson, Liqiang Chen, Robert J. Geraghty","doi":"10.1016/j.antiviral.2026.106356","DOIUrl":"10.1016/j.antiviral.2026.106356","url":null,"abstract":"<div><div>Human cytomegalovirus (HCMV) is a prevalent herpesvirus pathogen and remains a significant cause for mortality and morbidity in immunocompromised individuals and newborns. Like all viruses, HCMV uses host cellular proteins to facilitate virus replication and spread. Sirtuin 2 (SIRT2) is an NAD<sup>+</sup>-dependent deacetylase with a variety of substrates, including α-tubulin, where acetylation can alter function and stability. We have previously developed small molecule inhibitors targeting SIRT2 and in the current study, we show that two new compounds inhibit SIRT2 activity and also inhibit HCMV replication. The combination of these SIRT2 inhibitors with standard antivirals such as ganciclovir or letermovir resulted in a generally additive profile. Using indirect immunofluorescence, we determined that SIRT2 and SIRT1 expression was reduced over time in compound treated and untreated cells. We also observed SIRT2 and SIRT1 expression was increased in HCMV infected cells, compared to surrounding uninfected cells, regardless of compound treatment. GAPDH expression was stable over time and did not increase in HCMV infected cells, indicating a possible sirtuin-specific mechanism for upregulation of SIRT2 and 1 expression in infected cells. Further investigation is required to better understand the underlying anti-HCMV mechanism of action for our SIRT2 inhibitors and how HCMV infection impacts SIRT2 expression.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106356"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-29DOI: 10.1016/j.antiviral.2025.106339
Lauren Rodriguez , Yu Hu , Jiani Li , Dong Han , Nadine Peinovich , Clarissa Martinez , Pui Yan Ho , Jason K. Perry , Ross Martin , Onyema Ogbuagu , Amos Lichtman , Robert H. Hyland , Charlotte Hedskog
Obeldesivir is an oral nucleoside analog prodrug inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase Nsp12. This study evaluated baseline and treatment-emergent viral resistance to obeldesivir in participants from OAKTREE, a multicenter, double-blind trial wherein nonhospitalized adolescents and adults with COVID-19 at low risk of developing severe disease were randomized 1:1 to receive obeldesivir or placebo twice daily for 5 days. Deep sequencing was performed on mid-turbinate nasal swab samples collected on Days 1 (baseline), 3, 5, 10, 15, 20, and 29 from participants who met sequencing analysis criteria. Amino acid substitutions detected in the SARS-CoV-2 replication complex components were phenotyped in a replicon system. Overall, 1425 participants (obeldesivir, 725; placebo, 700) met sequencing analysis criteria and had baseline sequencing data. Thirty-five baseline Nsp12 substitutions, including P323L and G671S, were observed in ≥3 participants. Phenotyping of baseline Nsp12 substitutions showed obeldesivir half-maximal effective concentration (EC50) fold changes relative to wildtype that were within assay variability (≤2.15-fold). Among participants with baseline and postbaseline sequencing data, the proportion of emergent Nsp12 substitutions was similar between groups (obeldesivir, 35/208 [16.8 %]; placebo, 23/120 [19.2 %]). Twenty-five emergent Nsp12 substitutions were detected in the obeldesivir group but not in the placebo group. Only 1 emergent Nsp12 substitution (C799F) from 1 participant in the obeldesivir group was associated with reduced obeldesivir susceptibility, with a 3.35-fold change in EC50 versus wildtype. The low-to-no change in obeldesivir susceptibility among treatment-emergent Nsp12 substitutions indicated a high barrier to development of obeldesivir resistance in low-risk, nonhospitalized patients with COVID-19. ClinicalTrials.gov identifier: NCT05715528.
{"title":"SARS-CoV-2 resistance analyses from the Phase 3 OAKTREE study of obeldesivir in low-risk nonhospitalized participants with COVID-19","authors":"Lauren Rodriguez , Yu Hu , Jiani Li , Dong Han , Nadine Peinovich , Clarissa Martinez , Pui Yan Ho , Jason K. Perry , Ross Martin , Onyema Ogbuagu , Amos Lichtman , Robert H. Hyland , Charlotte Hedskog","doi":"10.1016/j.antiviral.2025.106339","DOIUrl":"10.1016/j.antiviral.2025.106339","url":null,"abstract":"<div><div>Obeldesivir is an oral nucleoside analog prodrug inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase Nsp12. This study evaluated baseline and treatment-emergent viral resistance to obeldesivir in participants from OAKTREE, a multicenter, double-blind trial wherein nonhospitalized adolescents and adults with COVID-19 at low risk of developing severe disease were randomized 1:1 to receive obeldesivir or placebo twice daily for 5 days. Deep sequencing was performed on mid-turbinate nasal swab samples collected on Days 1 (baseline), 3, 5, 10, 15, 20, and 29 from participants who met sequencing analysis criteria. Amino acid substitutions detected in the SARS-CoV-2 replication complex components were phenotyped in a replicon system. Overall, 1425 participants (obeldesivir, 725; placebo, 700) met sequencing analysis criteria and had baseline sequencing data. Thirty-five baseline Nsp12 substitutions, including P323L and G671S, were observed in ≥3 participants. Phenotyping of baseline Nsp12 substitutions showed obeldesivir half-maximal effective concentration (EC<sub>50</sub>) fold changes relative to wildtype that were within assay variability (≤2.15-fold). Among participants with baseline and postbaseline sequencing data, the proportion of emergent Nsp12 substitutions was similar between groups (obeldesivir, 35/208 [16.8 %]; placebo, 23/120 [19.2 %]). Twenty-five emergent Nsp12 substitutions were detected in the obeldesivir group but not in the placebo group. Only 1 emergent Nsp12 substitution (C799F) from 1 participant in the obeldesivir group was associated with reduced obeldesivir susceptibility, with a 3.35-fold change in EC<sub>50</sub> versus wildtype. The low-to-no change in obeldesivir susceptibility among treatment-emergent Nsp12 substitutions indicated a high barrier to development of obeldesivir resistance in low-risk, nonhospitalized patients with COVID-19. <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> identifier: NCT05715528.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106339"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-06DOI: 10.1016/j.antiviral.2026.106362
Sabine Wronski , Helena Obernolte , Dirk Schaudien , Armin Braun , Katherina Sewald , Anne Vaslin Chessex , Edouard Baulier , Christian Pasquali
Rhinovirus (RV), a common cold virus, is a predominant circulating virus which is increasingly recognized for its contribution to severe respiratory tract infections. Given the lack of vaccines, bacterial lysates are a promising alternative to prevent recurrent respiratory tract infections. OM-85, a bacterial lysate from 21 respiratory bacteria, has long been used safely as an oral drug to prevent recurrent respiratory tract infections in clinics. However, with inhalation emerging as preferred route to directly target the site of airway infection, OM-85 is being developed for local administration in the respiratory tract to enhance mucosal immunity.
This study evaluated the prophylactic efficacy of intranasally administered OM-85 in a murine model of RV infection. Mice were treated over a period of 12 days prior to RV infection and the immune response and viral load were assessed.
Intranasal administration of OM-85 primed the host immune response by the recruitment of innate immune cells to the lung, resulting in enhanced viral clearance. This was accompanied by a modulation of the RV-induced immune response toward a less pro-inflammatory phenotype, marked by substantial reduction of pro-inflammatory cytokines and neutrophil infiltration. The immune response was shifted towards an anti-inflammatory state supporting control of inflammation. Complementary precision-cut lung slice experiments confirmed the initial immune-priming activity of OM-85 independent of RV infection.
These findings demonstrate that local administration of OM-85 in the airways effectively primes the innate immune response and confers mucosal protective effects against RV-induced respiratory tract infection.
{"title":"Prophylactic intranasal administration of bacterial lysate OM-85 mitigates human rhinovirus (RV-A1b) lung infection and inflammation in mice","authors":"Sabine Wronski , Helena Obernolte , Dirk Schaudien , Armin Braun , Katherina Sewald , Anne Vaslin Chessex , Edouard Baulier , Christian Pasquali","doi":"10.1016/j.antiviral.2026.106362","DOIUrl":"10.1016/j.antiviral.2026.106362","url":null,"abstract":"<div><div>Rhinovirus (RV), a common cold virus, is a predominant circulating virus which is increasingly recognized for its contribution to severe respiratory tract infections. Given the lack of vaccines, bacterial lysates are a promising alternative to prevent recurrent respiratory tract infections. OM-85, a bacterial lysate from 21 respiratory bacteria, has long been used safely as an oral drug to prevent recurrent respiratory tract infections in clinics. However, with inhalation emerging as preferred route to directly target the site of airway infection, OM-85 is being developed for local administration in the respiratory tract to enhance mucosal immunity.</div><div>This study evaluated the prophylactic efficacy of intranasally administered OM-85 in a murine model of RV infection. Mice were treated over a period of 12 days prior to RV infection and the immune response and viral load were assessed.</div><div>Intranasal administration of OM-85 primed the host immune response by the recruitment of innate immune cells to the lung, resulting in enhanced viral clearance. This was accompanied by a modulation of the RV-induced immune response toward a less pro-inflammatory phenotype, marked by substantial reduction of pro-inflammatory cytokines and neutrophil infiltration. The immune response was shifted towards an anti-inflammatory state supporting control of inflammation. Complementary precision-cut lung slice experiments confirmed the initial immune-priming activity of OM-85 independent of RV infection.</div><div>These findings demonstrate that local administration of OM-85 in the airways effectively primes the innate immune response and confers mucosal protective effects against RV-induced respiratory tract infection.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106362"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-29DOI: 10.1016/j.antiviral.2026.106359
Yarong Song , Yitong Zeng , Han Zheng , Shu Shi , Zhongqing Li , Mingchen Liu , Sijin Shao , Ziheng Luo , Yurong Li , Jie Li , Kuanhui Xiang , Jie Wang
Chronic hepatitis B virus (HBV) infection is a major global health problem. Currently, existing antiviral drugs are difficult to achieve a functional cure for chronic hepatitis B (CHB). Therefore, it is necessary to develop new antiviral targets, especially those that can directly target HBV covalently closed circular DNA (cccDNA) in hepatocytes. Here, we identified a conserved SOX6 binding site in the enhancer I (ENI) region of the HBV genome, and found that SOX6 promotes the replication of multiple genotypes HBV through its HMG domain. Mechanistically, SOX6 binds to the conserved binding site located in the HBV ENI region through its HMG domain, thereby promoting HBV replication by enhancing the transcriptional activity of ENI. Moreover, cisplatin and doxorubicin not only promote HBV replication but also promote SOX6 expression. Knocking down the expression of endogenous SOX6 or mutating the SOX6 binding site in the HBV ENI region significantly weakens the direct promoting effect of cisplatin and doxorubicin on HBV replication. In summary, SOX6 promotes HBV replication by enhancing the transcriptional activity of HBV ENI through its HMG domain, suggesting that it can serve as a potential target for regulating HBV cccDNA transcription. In addition, SOX6 participates in the direct promotion of HBV replication by cisplatin and doxorubicin, providing new insights into the molecular mechanisms of tumor chemotherapy related HBV reactivation (HBVr) and potential targets for the prevention of HBVr during tumor chemotherapy.
{"title":"SOX6 is a novel host factor that promotes hepatitis B virus replication by enhancing the transcriptional activity of enhancer I","authors":"Yarong Song , Yitong Zeng , Han Zheng , Shu Shi , Zhongqing Li , Mingchen Liu , Sijin Shao , Ziheng Luo , Yurong Li , Jie Li , Kuanhui Xiang , Jie Wang","doi":"10.1016/j.antiviral.2026.106359","DOIUrl":"10.1016/j.antiviral.2026.106359","url":null,"abstract":"<div><div>Chronic hepatitis B virus (HBV) infection is a major global health problem. Currently, existing antiviral drugs are difficult to achieve a functional cure for chronic hepatitis B (CHB). Therefore, it is necessary to develop new antiviral targets, especially those that can directly target HBV covalently closed circular DNA (cccDNA) in hepatocytes. Here, we identified a conserved SOX6 binding site in the enhancer I (ENI) region of the HBV genome, and found that SOX6 promotes the replication of multiple genotypes HBV through its HMG domain. Mechanistically, SOX6 binds to the conserved binding site located in the HBV ENI region through its HMG domain, thereby promoting HBV replication by enhancing the transcriptional activity of ENI. Moreover, cisplatin and doxorubicin not only promote HBV replication but also promote SOX6 expression. Knocking down the expression of endogenous SOX6 or mutating the SOX6 binding site in the HBV ENI region significantly weakens the direct promoting effect of cisplatin and doxorubicin on HBV replication. In summary, SOX6 promotes HBV replication by enhancing the transcriptional activity of HBV ENI through its HMG domain, suggesting that it can serve as a potential target for regulating HBV cccDNA transcription. In addition, SOX6 participates in the direct promotion of HBV replication by cisplatin and doxorubicin, providing new insights into the molecular mechanisms of tumor chemotherapy related HBV reactivation (HBVr) and potential targets for the prevention of HBVr during tumor chemotherapy.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106359"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-20DOI: 10.1016/j.antiviral.2026.106353
Laura Corneillie, Léa Mézière, Claire Montpellier, Benjamin Drouet, Cécile-Marie Aliouat-Denis, Laurence Cocquerel
Hepatitis E virus (HEV) is an emerging zoonotic pathogen and the leading cause of acute viral hepatitis worldwide. Nevertheless, HEV remains largely underestimated and poorly controlled. HEV infects a broad range of host species, transmits through diverse routes and can cause chronic infections in immunocompromised individuals and severe hepatitis in pregnant women. Currently, there is no HEV-specific antiviral treatment available and the only licensed vaccine is restricted to a few countries. Taken together, this highlights its significance as a global health treat and underscores the urgent need for new preventive and therapeutic strategies.
This review provides a comprehensive overview of HEV molecular and cellular biology with a focus on antiviral opportunities. First, we summarize the epidemiology and clinical spectrum of HEV infection, as well as the current prevention, vaccination and treatment strategies. Next, we review the molecular mechanisms underlying HEV entry, replication, and assembly/egress, detailing host and viral factors that represent promising antiviral targets. We present the available in vitro and in vivo experimental models that are essential for studying the HEV life cycle and evaluating therapeutic candidates.
Particular attention is given to recent discoveries in HEV entry pathways, the organization and functions of the ORF1 replicase complex, and host-virus interactions. Importantly, we provide an up-to-date overview of host-targeting antivirals (HTAs) and direct-acting antivirals (DAAs) against HEV that have been identified so far. This review emphasizes how fundamental virology informs drug discovery and paves the way toward the development of effective antivirals against this underestimated pathogen of increasing global concern.
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Pub Date : 2026-03-01Epub Date: 2026-02-02DOI: 10.1016/j.antiviral.2026.106361
Amandeep Kaur , Ugo Alaribe , Joseph Varon , Sidra Hassaan , Matthew Halma
Measles remains one of the most contagious viral infections, and its resurgence due to declining global vaccination coverage has renewed interest in therapeutic and preventive strategies. This systematic review analyzes current and emerging acute therapies and their relationship to measles virology and clinical outcomes. A systematic search of PubMed, Scopus, Web of Science, China National Knowledge Infrastructure and Google Scholar (1990–2025) was conducted using predefined inclusion and exclusion criteria to identify clinical studies on acute measles treatment. Despite being used off-label, ribavirin and interferon-α have demonstrated reductions in severity and complications in small clinical trials and case reports. Vitamin A supplementation remains the only widely recommended therapy with strong evidence for reducing morbidity and mortality, particularly in children with deficiency. Traditional Chinese medications such as Tanreqing and Xiyanping show symptomatic improvement but require mechanistic validation. Investigational therapeutics, including polymerase inhibitors such as ERDRP-0519, monoclonal antibodies targeting the fusion protein, and antiviral candidates such as remdesivir, offer promising future options. While vaccination remains essential, adjunctive therapies provide additional tools to reduce complications in under-vaccinated populations.
麻疹仍然是最具传染性的病毒感染之一，由于全球疫苗接种覆盖率下降，麻疹的死灰复燃使人们重新关注治疗和预防战略。本系统综述分析了当前和新出现的急性治疗方法及其与麻疹病毒学和临床结果的关系。系统检索PubMed、Scopus、Web of Science、中国国家知识基础设施和谷歌Scholar（1990-2025）数据库，采用预定义的纳入和排除标准确定急性麻疹治疗的临床研究。在小型临床试验和病例报告中，利巴韦林和干扰素-α被证明可以降低严重程度和并发症。补充维生素A仍然是唯一被广泛推荐的治疗方法，有强有力的证据表明可以降低发病率和死亡率，特别是在缺乏维生素A的儿童中。中药如痰热清和喜炎平可改善症状，但需要机制验证。包括聚合酶抑制剂（如ERDRP-0519）、靶向融合蛋白的单克隆抗体和抗病毒候选药物（如remdesivir）在内的研究性治疗为未来提供了有希望的选择。虽然疫苗接种仍然是必不可少的，但辅助治疗为减少疫苗接种不足人群的并发症提供了额外的工具。
{"title":"Acute management of measles: A systematic review of therapeutic strategies","authors":"Amandeep Kaur , Ugo Alaribe , Joseph Varon , Sidra Hassaan , Matthew Halma","doi":"10.1016/j.antiviral.2026.106361","DOIUrl":"10.1016/j.antiviral.2026.106361","url":null,"abstract":"<div><div>Measles remains one of the most contagious viral infections, and its resurgence due to declining global vaccination coverage has renewed interest in therapeutic and preventive strategies. This systematic review analyzes current and emerging acute therapies and their relationship to measles virology and clinical outcomes. A systematic search of PubMed, Scopus, Web of Science, China National Knowledge Infrastructure and Google Scholar (1990–2025) was conducted using predefined inclusion and exclusion criteria to identify clinical studies on acute measles treatment. Despite being used off-label, ribavirin and interferon-α have demonstrated reductions in severity and complications in small clinical trials and case reports. Vitamin A supplementation remains the only widely recommended therapy with strong evidence for reducing morbidity and mortality, particularly in children with deficiency. Traditional Chinese medications such as Tanreqing and Xiyanping show symptomatic improvement but require mechanistic validation. Investigational therapeutics, including polymerase inhibitors such as ERDRP-0519, monoclonal antibodies targeting the fusion protein, and antiviral candidates such as remdesivir, offer promising future options. While vaccination remains essential, adjunctive therapies provide additional tools to reduce complications in under-vaccinated populations.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106361"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-22DOI: 10.1016/j.antiviral.2025.106337
Stephen R. Welch , Jessica R. Spengler , Sarah C. Genzer , Jessica R. Harmon , JoAnn D. Coleman-McCray , Teresa E. Sorvillo , Stuart T. Nichol , Christina F. Spiropoulou
Defective interfering particles (DIPs) are naturally occurring virus-like particles containing truncated fragments of the parental viral genome and have gained interest as potential medical countermeasures (MCMs) against viral infections. Using the Syrian hamster model of Nipah virus (NiV) disease, we previously showed that treatment with artificially produced NiV-derived DIPs markedly reduced clinical signs and mortality. However, DIP production required infectious NiV and BSL-4 containment, creating a major barrier to clinical translation. Here, we describe an improved, non-infectious, BSL-2-compatible NiV replicon system for DIP generation that eliminates the need for infectious virus. DIPs produced using this system inhibited virus in vitro and retained full protective efficacy in hamsters. By removing the requirement for high-containment virus, this approach overcomes key regulatory and practical hurdles, enabling advancement of DIP-based therapeutics toward clinical evaluation and eventual use against NiV and related henipaviruses.
{"title":"Nipah virus-derived defective interfering particles generated using non-infectious viral replicon particles confer protective efficacy comparable to those produced with standard full-length infectious virus","authors":"Stephen R. Welch , Jessica R. Spengler , Sarah C. Genzer , Jessica R. Harmon , JoAnn D. Coleman-McCray , Teresa E. Sorvillo , Stuart T. Nichol , Christina F. Spiropoulou","doi":"10.1016/j.antiviral.2025.106337","DOIUrl":"10.1016/j.antiviral.2025.106337","url":null,"abstract":"<div><div>Defective interfering particles (DIPs) are naturally occurring virus-like particles containing truncated fragments of the parental viral genome and have gained interest as potential medical countermeasures (MCMs) against viral infections. Using the Syrian hamster model of Nipah virus (NiV) disease, we previously showed that treatment with artificially produced NiV-derived DIPs markedly reduced clinical signs and mortality. However, DIP production required infectious NiV and BSL-4 containment, creating a major barrier to clinical translation. Here, we describe an improved, non-infectious, BSL-2-compatible NiV replicon system for DIP generation that eliminates the need for infectious virus. DIPs produced using this system inhibited virus <em>in vitro</em> and retained full protective efficacy in hamsters. By removing the requirement for high-containment virus, this approach overcomes key regulatory and practical hurdles, enabling advancement of DIP-based therapeutics toward clinical evaluation and eventual use against NiV and related henipaviruses.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"246 ","pages":"Article 106337"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145826728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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