Antiviral research最新文献

{"title":"Seeking innovative concepts in development of antiviral drug combinations","authors":"Denis E. Kainov ,&nbsp;Erlend Ravlo ,&nbsp;Aleksandr Ianevski","doi":"10.1016/j.antiviral.2025.106079","DOIUrl":"10.1016/j.antiviral.2025.106079","url":null,"abstract":"<div><div>Antiviral drugs are crucial for managing viral infections, but current treatment options remain limited, particularly for emerging viruses. These drugs can be classified based on their chemical composition, including neutralizing antibodies (nAbs), recombinant human receptors (rhRs), antiviral CRISPR/Cas systems, interferons, antiviral peptides (APs), antiviral nucleic acid polymers, and small molecules. Some of these agents target viral factors, host factors, or both. A major challenge for virus-targeted treatments is their narrow-spectrum effectiveness and the potential for drug resistance, while host-directed and virus/host-targeted therapies often suffer from significant side effects. The synergistic combination of multiple antiviral drugs holds promise for improving treatment outcomes by targeting different stages of the viral life cycle, reducing resistance, and minimizing side effects. However, developing such drug combinations presents its own set of challenges. Several drug combinations could be optimized, and new combinations developed by using AI, to more effectively treat both emerging and re-emerging viral infections.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"234 ","pages":"Article 106079"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and biological evaluation of novel 2′-deoxy-2′-spirooxetane-7-deazapurine nucleoside analogs as anti-SARS-CoV-2 agents","authors":"Minli Gao ,&nbsp;Zhaoyong Zhang ,&nbsp;Guoqiang Yao ,&nbsp;Lu Zhang ,&nbsp;Anna Duan ,&nbsp;Yuanyuan Zhang ,&nbsp;Yanqun Wang ,&nbsp;Jincun Zhao ,&nbsp;Jiancun Zhang","doi":"10.1016/j.antiviral.2024.106060","DOIUrl":"10.1016/j.antiviral.2024.106060","url":null,"abstract":"<div><div>The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global public health crisis and continues to pose grave threats to human health. The efficacy of current vaccines and therapeutics is likely limited for future emerging strains due to the highly mutative nature of the virus, underscoring an urgent need for the development of new, potent antiviral agents. In this study, we report the design and synthesis of a series of novel 2′-deoxy-2′-spirooxetane-7-deazapurine nucleoside analogs as potential inhibitors of SARS-CoV-2 replication. Some of these compounds demonstrate potent antiviral activity, offering a potential new weapon for therapeutic intervention against the ever-evolving SARS-CoV-2 virus. Among the tested compounds, nucleoside analog <strong>11q</strong> exhibited the most potent antiviral activity against SARS-CoV-2 in Vero E6 cells, with IC₅₀ values of 0.14 μM for the wild-type strain and 0.36 μM for the BA.5 strain. Notably, compound <strong>11q</strong> exhibits up to nine times greater inhibitory activity against wild-type SARS-CoV-2 compared to Remdesivir and also possesses a superior selectivity index. These findings suggest that compound <strong>11q</strong> is a highly promising lead candidate for future drug development aimed at combating SARS-CoV-2.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"234 ","pages":"Article 106060"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913680","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}

{"title":"Nucleotide analogues and mpox: Repurposing the repurposable","authors":"Ashleigh Shannon,&nbsp;Bruno Canard","doi":"10.1016/j.antiviral.2024.106057","DOIUrl":"10.1016/j.antiviral.2024.106057","url":null,"abstract":"<div><div>While the COVID-19 crisis is still ongoing, a new public health threat has emerged with recent outbreaks of monkeypox (mpox) infections in Africa. Mass vaccination is not currently recommended by the World Health Organization (WHO), and antiviral treatments are yet to be specifically approved for mpox, although existing FDA-approved drugs (Tecovirimat, Brincidofovir, and Cidofovir) may be used in severe cases or for immunocompromised patients. A first-line of defense is thus drug repurposing, which was heavily attempted against SARS-CoV-2 - albeit with limited success. This review focuses on nucleoside analogues as promising antiviral candidates for targeting of the viral DNA-dependent DNA polymerase. In contrast to broad-spectrum screening approaches employed for SARS-CoV-2, we emphasize the importance of understanding the structural specificity of viral polymerases for rational selection of potential candidates. By comparing DNA-dependent DNA polymerases with other viral polymerases, we highlight the unique features that influence the efficacy and selectivity of nucleoside analogues. These structural insights provide a framework for the preselection, repurposing, optimization, and design of nucleoside analogues, aiming to accelerate the development of targeted antiviral therapies for mpox and other viral infections.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"234 ","pages":"Article 106057"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852243","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}

{"title":"Host-targeting antivirals for chronic viral infections of the liver","authors":"Nicola Frericks ,&nbsp;Mara Klöhn ,&nbsp;Frauke Lange ,&nbsp;Lilli Pottkämper ,&nbsp;Arnaud Carpentier ,&nbsp;Eike Steinmann","doi":"10.1016/j.antiviral.2024.106062","DOIUrl":"10.1016/j.antiviral.2024.106062","url":null,"abstract":"<div><div>Infection with one or several of the five known hepatitis viruses is a leading cause of liver disease and poses a high risk of developing hepatocellular carcinoma upon chronic infection. Chronicity is primarily caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) and poses a significant health burden worldwide. Co-infection of chronic HBV infected patients with hepatitis D virus (HDV) is less common but is marked as the most severe form of chronic viral hepatitis. Hepatitis A virus (HAV) and hepatitis E virus (HEV) primarily cause self-limiting acute hepatitis. However, studies have also reported chronic progression of HEV disease in immunocompromised patients. While considerable progress has been made in the treatment of HCV and HBV through the development of direct-acting antivirals (DAAs), challenges including drug resistance, incomplete viral suppression resulting in failure to achieve clearance and the lack of effective treatment options for HDV and HEV remain. Host-targeting antivirals (HTAs) have emerged as a promising alternative approach to DAAs and aim to disrupt virus-host interactions by modulating host cell pathways that are hijacked during the viral replication cycle. The aim of this review is to provide a comprehensive overview about the major milestones in research and development of HTAs for chronic HBV/HDV and HCV infections. It also summarizes the current state of knowledge on promising host-targeting therapeutic options against HEV infection.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"234 ","pages":"Article 106062"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of mechanisms of the rabies virus P protein-nucleocapsid interaction using engineered N-protein peptides and potential applications in antivirals design","authors":"Jingyu Zhan ,&nbsp;Shatabdi Chakraborty ,&nbsp;Ashish Sethi ,&nbsp;Yee-Foong Mok ,&nbsp;Fei Yan ,&nbsp;Gregory W. Moseley ,&nbsp;Paul R. Gooley","doi":"10.1016/j.antiviral.2024.106075","DOIUrl":"10.1016/j.antiviral.2024.106075","url":null,"abstract":"<div><div>The Phosphoprotein (P protein) of the rabies virus has multiple roles in virus replication. A critical function is to act as a cofactor in genome replication and mRNA production through binding <em>via</em> its N-terminal region to the L protein, the essential enzyme for mRNA and genome synthesis/processing, and <em>via</em> its C-terminal domain (P_CTD) to the N protein and viral RNA (N-RNA) ribonucleoprotein complex. The binding site of the P_CTD on the N protein is a disordered loop that is expected to be phosphorylated at Ser389. This interface may provide novel targets for antiviral approaches. Following an alanine scan of the peptide we selected two single site mutations that showed improved affinity and combined these mutations with a phosphomimetic (S389E) to produce double and triple mutants in the context of linear and cyclic peptides of the disordered loop, with the goal of generating a competitive peptide against the N-RNA complex. To assess the binding properties of the peptides we characterized their thermodynamics identifying complex properties of improved enthalpy but with compensating entropy for mutants and cyclized peptides. Nevertheless, a triple mutant shows 3.5-fold stronger affinity for P_CTD than the full-length S389E N protein. Structural characterization of the triple mutant suggests the improved affinity may be due to trapping a favoured β-strand structure for binding to the P_CTD. This novel peptide may serve as a template for the future design of antivirals.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"234 ","pages":"Article 106075"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiviral drug discovery with an optimized biochemical dengue protease assay: Improved predictive power for antiviral efficacy","authors":"Johannes Lang ,&nbsp;Sudip Kumar Dutta ,&nbsp;Mila M. Leuthold ,&nbsp;Lisa Reichert ,&nbsp;Nikos Kühl ,&nbsp;Byron Martina ,&nbsp;Christian D. Klein","doi":"10.1016/j.antiviral.2024.106053","DOIUrl":"10.1016/j.antiviral.2024.106053","url":null,"abstract":"<div><div>The viral NS2B-NS3 protease is a promising drug target to combat dengue virus (DENV) and other emerging flaviviruses. The discovery of novel DENV protease inhibitors with antiviral efficacy is hampered by the low predictive power of biochemical assays. We herein present a comparative evaluation of biochemical DENV protease assay conditions and their benchmarking against antiviral efficacy and a protease-specific reporter gene assay. Variations were performed with respect to pH, type of detergent, buffer, and substrate. The revised assay conditions were applied in a medicinal chemistry effort aimed at phenylglycine protease inhibitors. This validation study demonstrated a considerably improved predictive power for antiviral efficacy in comparison to previous approaches. An extensive evaluation of phenylglycine-based DENV protease inhibitors with highly diverse N-terminal caps indicates further development potential in this structural region. Furthermore, the phenylglycine moiety may be less essential than previously assumed, providing a development option towards reduced lipophilicity and thereby an improved pharmacokinetic and toxicity profile.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"234 ","pages":"Article 106053"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High HIV-1 viremia and low anti-Env antibody responses are associated with delayed treatment response to fostemsavir in highly treatment-experienced individuals","authors":"Svenja Weiss ,&nbsp;Raymond A. Alvarez ,&nbsp;Marisa Goff ,&nbsp;Hongru Li ,&nbsp;Eric Acosta ,&nbsp;Ping Chen ,&nbsp;Helen M. Seedhom ,&nbsp;Talia H. Swartz ,&nbsp;Margaret Gartland ,&nbsp;Andrew Clark ,&nbsp;Judith A. Aberg ,&nbsp;Benjamin K. Chen","doi":"10.1016/j.antiviral.2025.106096","DOIUrl":"10.1016/j.antiviral.2025.106096","url":null,"abstract":"<div><div>Fostemsavir (FTR) is an approved first-in-class small molecule Env antagonist for treating multi-drug resistant (MDR) HIV-1 infection. In the BRIGHTE study, viral suppression rates in heavily treatment-experienced people with HIV (PWH) increased from week 48 through week 96. Factors that contribute to this late response are not well understood. Given FTR's ability to stabilize a native HIV-1 envelope trimer conformational state, we examined anti-HIV humoral immune responses in the BRIGHTE study to explore how evolving antibody responses in the presence of drug correlate with delayed viral suppression. 16 BRIGHTE study participants (ppt) were selected based on their time to first viremic suppression: eight early (EVS) and eight late viral suppressors (LVS). Immune responses were also analyzed in eight ppt from the SAILING study that evaluated dolutegravir. Anti-HIV Env IgG titer, cell-free and cell-to-cell neutralization activity, FcγRIIa- and FcγRIIIa-signaling, and plasma cytokines at weeks 0, 4 and 108 were examined and correlated with clinical variables associated with treatment response. FTR treatment did not significantly enhance antibody responses against reference strain of HIV in LVS compared to EVS. However, at baseline, LVS had significantly lower anti-HIV IgG titers, higher VL, lower CD4⁺ T-cell counts and experienced greater increases in CD4⁺ T-cell counts than EVS. Additionally, IL-8 levels were increased in LVS vs. EVS at treatment initiation. In comparison, SAILING ppt showed increased FcγRIIa signaling during drug treatment compared to the FTR groups. Further studies will determine if pre-treatment characteristics influence timing to viral suppression in FTR-treated individuals with MDR-HIV.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"235 ","pages":"Article 106096"},"PeriodicalIF":4.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073759","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}

{"title":"DExD-box RNA helicases in human viral infections: Pro- and anti-viral functions","authors":"Paul T. Winnard Jr. ,&nbsp;Farhad Vesuna ,&nbsp;Venu Raman","doi":"10.1016/j.antiviral.2025.106098","DOIUrl":"10.1016/j.antiviral.2025.106098","url":null,"abstract":"<div><div>Viruses have co-evolved with their hosts, intertwining their life cycles. As a result, components and pathways from a host cell's processes are appropriated for virus infection. This review examines the host DExD-box RNA helicases known to influence virus infection during human infections. We have identified 42 species of viruses (28 genera and 21 families) whose life cycles are modulated by at least one, but often multiple, DExD-box RNA helicases. Of these, 37 species require one or multiple DExD-box RNA helicases for efficient infections, i.e., in these cases the DExD-box RNA helicases are pro-viral. However, similar evolutionary processes have also led to cellular responses that combat viral infections. In humans, these responses comprise intrinsic and innate immune responses initiated and regulated by some of the same DExD-box RNA helicases that act as pro-viral helicases. Currently, anti-viral DExD-box RNA helicase responses to viral infections are noted in 23 viral species. Notably, most studied viruses are linked to severe, life-threatening diseases, leading many researchers to focus on DExD-box RNA helicases as potential therapeutic targets. Thus, we present examples of host-directed therapies targeting anti-viral DExD-box RNA helicases. Overall, our findings indicate that various DExD-box RNA helicases serve as either pro- and/or anti-viral agents across a wide range of viruses. Continued investigation into the pro-viral activities of these helicases will help identify specific protein motifs that can be targeted by drugs to manage or eliminate the severe diseases caused by these viruses. Comparative studies on anti-viral DExD-box RNA helicase responses may also offer insights for developing therapies that enhance immune responses triggered by these helicases.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"235 ","pages":"Article 106098"},"PeriodicalIF":4.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073757","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}

{"title":"Ensitrelvir treatment–emergent amino acid substitutions in SARS-CoV-2 3CLpro detected in the SCORPIO-SR phase 3 trial","authors":"Takeki Uehara ,&nbsp;Hiroshi Yotsuyanagi ,&nbsp;Norio Ohmagari ,&nbsp;Yohei Doi ,&nbsp;Masaya Yamato ,&nbsp;Takumi Imamura ,&nbsp;Hiroki Sakaguchi ,&nbsp;Akimasa Fukushi ,&nbsp;Yosuke Takeda ,&nbsp;Keiko Baba ,&nbsp;Haruaki Nobori ,&nbsp;Tadashi Miyamoto ,&nbsp;Shuhei Arita ,&nbsp;Reiko Dodo ,&nbsp;Alice Shimba ,&nbsp;Keita Fukao ,&nbsp;Takao Shishido ,&nbsp;Yuko Tsuge ,&nbsp;Hiroshi Mukae","doi":"10.1016/j.antiviral.2025.106097","DOIUrl":"10.1016/j.antiviral.2025.106097","url":null,"abstract":"<div><div>The impact of treatment-emergent amino acid substitutions (TEAASs) in severe acute coronavirus 2 (SARS-CoV-2) 3C-like protease (3CL^pro) on clinical and virologic outcomes was evaluated in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) who received ensitrelvir 125 mg in the SCORPIO-SR trial. Individuals were randomised to ensitrelvir or matched placebo once daily for 5 days (first dose &lt;72 h after disease onset). 3CL^pro-TEAASs were identified by sequencing <em>nsp5</em> encoding 3CL^pro from pre- and post-treatment nasopharyngeal swabs. Time to resolution of a composite of five characteristic COVID-19 symptoms (TTR) was compared between patients with and without the most common 3CL^pro-TEAASs in the ensitrelvir arm. The ensitrelvir and placebo intention-to-treat populations comprised 345 and 341 patients, respectively. 3CL^pro-TEAASs were detected in 19/204 (9.3%) ensitrelvir-treated and 3/137 (2.2%) placebo-treated patients with paired sequence data. The most common 3CL^pro-TEAASs in the ensitrelvir arm were M49L (n = 12), M49I (n = 3) and S144A (n = 2). In the placebo arm, all 3CL^pro-TEAASs occurred in ≤1 patient. Median (95% confidence interval) TTR was comparable between patients with and without those TEAASs (158.8 h [112.1–281.9] vs 189.7 h [151.4–234.4]). Mean viral RNA levels declined more slowly in patients with M49L/I or S144A versus those without. Reductions in viral titre were unaffected by these TEAASs. The characteristics of recombinant SARS-CoV-2 with 3CL^pro mutations were explored <em>in vitro</em>. Recombinant viruses with some 3CL^pro mutations had reduced susceptibility to ensitrelvir <em>in vitro</em>, with limited effects on viral and competitive fitness. Continued surveillance is warranted to monitor the spread of viruses with 3CL^pro mutations.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"236 ","pages":"Article 106097"},"PeriodicalIF":4.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune evasion of Omicron variants JN.1, KP.2, and KP.3 to the polyclonal and monoclonal antibodies from COVID-19 convalescents and vaccine recipients","authors":"Qian Wu ,&nbsp;Hairuo Wu ,&nbsp;Yabin Hu ,&nbsp;Xingyu Zheng ,&nbsp;Fangfang Chang ,&nbsp;Yongchen Liu ,&nbsp;Zhendong Pan ,&nbsp;Qijie Wang ,&nbsp;Fei Tang ,&nbsp;Jun Qian ,&nbsp;Yuezhou Li ,&nbsp;Bin Huang ,&nbsp;Keqiu Chen ,&nbsp;Juan Xu ,&nbsp;You Wang ,&nbsp;Xiangping Xie ,&nbsp;Ping Zhao ,&nbsp;Xu Wu ,&nbsp;Xiaowang Qu ,&nbsp;Yi-Ping Li","doi":"10.1016/j.antiviral.2025.106092","DOIUrl":"10.1016/j.antiviral.2025.106092","url":null,"abstract":"<div><div>The Omicron BA.2.86 subvariants, JN.1, KP.2, and KP.3, have become predominant globally, raising concerns about their immune evasion from vaccines and monoclonal antibody (mAb) treatments. These variants harbor more receptor-binding domain (RBD) mutations than the XBB and EG.5 sub-lineages, which are already known to compromise vaccine and therapeutic efficacy. We evaluated sera from individuals vaccinated with inactivated vaccines, with or without breakthrough infections, as well as COVID-19 convalescents. Our results showed a substantial decrease in serum neutralizing activity against the JN.1, KP.2, XBB.1.5, and EG.5.1 variants compared to BA.2. Additionally, we developed 19 neutralizing antibodies from memory B cells, with some retaining efficacy against earlier Omicron variants. However, potency was notably diminished against newer subvariants like BF.7, BQ.1, XBB.1.5, and BA.2.86. Of mAbs, those isolated from COVID-19 convalescents, particularly SA-3, exhibited exceptional potency across ten variants from BA.2 to KP.2, with IC50 values ranging from 0.006 to 2.546 μg/mL. However, SA-3 had lost neutralizing activity against the KP.3 due to the Q493E mutation, but the KP.3 became susceptible to neutralization by the other mAb, SA-6. In contrast, SA-6 was unable to neutralize KP.2 because of the presence of R346T mutation. Our findings underscore the importance of continuous surveillance of viral evolution and the need for updated vaccines and therapeutics to combat the ongoing evolution of SARS-CoV-2, particularly in the context of emerging variants that escape both vaccine-induced immunity and monoclonal antibody treatments.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"235 ","pages":"Article 106092"},"PeriodicalIF":4.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045446","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}