Influenza A virus (IAV) is one of the most important zoonotic pathogens and can cause global influenza pandemics and seasonal influenza outbreaks. Generation of recombinant IAV expressing a fluorescent protein will allow the infection to be easily monitored. In this study, we initially constructed a replication-defective H1N1/ΔPB2-GFP and a replication-competent H1N1/NS-GFP. However, these two reporter IAVs exhibited genetic instability. To stabilize the recombinant viral genome, we recoded the gfp sequence (rGFP) using synonymous codons to mimic the high-NP-binding regions involved in NP-vRNA interaction. This approach resulted in the development of replication-defective H1N1/ΔPB2(300)-rGFP and replication-competent H1N1/NS-rGFP, both of which exhibited enhanced stability in GFP expression. By replacing the HA segment from strain A/mink/China/CY 2017 (H5N1), we also generated a replication-defective H5N1/ΔPB2(300)-rGFP, which showed excellent genetic stability. Using these reporter IAVs, the blocking of virus infection by neutralizing antibodies and antivirals can be rapidly detected by the loss of fluorescent reporter expression. Replication-defective reporter IAVs constructed in this study can only infect and replicate in cells expressing PB2, allowing the possibility of manipulation of highly pathogenic IAV and their related reassortant strains in biosafety level-2 laboratories. Our data highlight the importance of NP-vRNA interaction for the stability of IAV genome, and the reporter IAVs generated using this strategy could be powerful tools for both basic and applied influenza virus research.

Comparably few lineages of influenza A virus (IAV) have evolved long-term sustained transmission in mammals. The reasons remain largely unknown, and the possibility of avian IAVs evolving sustained mammalian transmission is an ongoing concern. Here we measured the GC content and frequency of GC dinucleotides in 115,520 whole genomes of IAVs using bioinformatic analyses. We found that persistent mammalian lineages showed declining trends in GC-related content and could be reliably separated from IAVs circulating only in birds and those sporadically infecting mammals. Similarly, the earliest viruses of persistent mammalian lineages showed reduced GC-related content, suggesting that this trait might in part contribute to their eventual persistence. Recent highly pathogenic 2.3.4.4b H5 viruses that spread in mink, foxes and humans were also characterized by reduced GC-related content. While not sufficient, reduced GC-related content may be a necessary condition for sustained mammalian transmission and should be included in risk assessment tools for pandemic influenza.

Influenza viruses are highly prevalent and continuously evolving respiratory pathogens that pose a significant threat to global public health and the poultry industry. Immunization remains the primary approach to preventing infection and reducing the risk of an influenza pandemic. Nanoparticles not only serve as delivery vehicles for antigens but also enhance antigen-specific immune responses. Polysaccharide nanoparticles not only amplify the immunostimulatory capacity of polysaccharides but also exhibit superior adjuvant effects. In this study, we investigated the effect of cationic Lentinan (CLNT) as an adjuvant for influenza vaccines. CLNT significantly enhanced the production of specific antibodies against influenza antigens (H1N1 and H9N2) and promoted a strong humoral immune response. Compared with the control group, the CLNT group showed 8.49- and 5.23-fold increases in H1N1- and H9N2-specific IgG antibody levels, respectively. CLNT also activated dendritic cells, T cells, and B cells, thus triggering the cellular immune response. In addition, CLNT effectively inhibited the replication of H1N1 and H9N2 viruses in the trachea and lungs, indicating its potent protective immune effect against influenza virus challenge. This study suggests that CLNT enhances both the potency and breadth of immune responses against influenza viruses, presenting it as a promising adjuvant and offering new options for designing next-generation influenza vaccines.

Seasonal and pandemic influenza viruses are continuous threats to human health, requiring rapid development of vaccines to multiple evolving viral strains. RNA vaccine technologies have the adaptability and manufacturability to facilitate pandemic preparedness but have limited flexibility in their route of administration, reducing the ability to establish local protective immune responses such as respiratory mucosal immunity. Here, we describe monovalent and bivalent replicon vaccines against A/Vietnam/1203/2004 H5N1 and A/Anhui/PA-1/2013 H7N9. These replicon vaccines express either H5 or H7 hemagglutinin and are formulated with a nanostructured lipid carrier (NLC) that permits both intramuscular (IM) and intranasal (IN) dosing. In mice, IM vaccination established systemic humoral and cellular responses but no detectable mucosal response, while IN administration induced robust systemic and mucosal immunity. The replicon-NLC vaccines protected against morbidity and mortality in ferret challenge models, establishing this intranasally-administered replicon-NLC vaccine platform as a potential pandemic response tool.

Discovery of monoterpenoid-based benzamides bearing bicyclo[2.2.1]heptane motif as influenza H1N1 virus inhibitors.

BackgroundInfluenza A viruses pose a persistent pandemic threat due to their zoonotic potential and capability of antigenic shift, enabling the emergence of novel strains with pandemic potential.MethodsThis parallel design, dose-ranging, blinded study, assessed the safety and immunogenicity of three dose-levels (12.5, 25 and 50 µg) of mRNA-1018. This pre-pandemic vaccine, which encodes for the hemagglutinin (HA) of H5-A/chicken/Ghana/2021, was given as two doses 21 days apart to 304 healthy adults (> 18 to < 65 and > 65 years of age). Immune responses were assessed by hemagglutination inhibition (HAI) and microneutralization (MN) at multiple time points during the 6-month study.ResultsMost local and systemic solicited adverse reactions (AR) were Grade 1–2, and the most common AR were injection site pain, fatigue, and headache. Grade 3 AR were infrequent (< 5%), and no Grade 4 events occurred. The rates of solicited AR following the second dose were comparable to the first, with no notable increase in severity. One related SAE (syncope) was reported.Three weeks after the second dose, the percentage of participants in all dose groups with HAI titers ≥ 1:40 (defined as seroprotection or SP) were 97.8% (95% confidence interval [95%CI]: 95.4, 99.2). The percentage with seroconversion (SC) by HAI (defined as post-vaccination titer ≥ 1:40 if baseline is < 1:10 or a 4-fold or greater rise if baseline is ≥ 1:10) was 97.1% (95%CI: 94.4–98.7). Immune responses were detected early across all dose groups and remained detectable at study end. Three weeks after the first dose, 79.5% (95%CI: 74.3, 84.1) of participants had achieved SP and 78.1% (95%CI: 72.8, 82.8) met criteria for SC. Six months after the second dose, 70.6 % (95%CI: 64.8, 76.0) maintained SP levels. Titers measured by both HAI and microneutralization (MN) assays increased with increasing dose of mRNA-1018.ConclusionAcross all dose levels, mRNA-1018 was safe, well-tolerated, and demonstrated rapid and persistent immune response which are considered key attributes of a pandemic vaccine.DisclosuresAll Authors: No reported disclosures

Introduction:The COVID-19 pandemic and subsequent influenza outbreaks highlighted disparities in timely access to tests and treatments. To address this gap, a nationwide Home Test to Treat (HTTT) program was launched to provide home test kits, telehealth consultations, and medication delivery for COVID-19 and influenza. This study explored participant experiences, factors influencing satisfaction levels, and recommendations for future programs.MethodsIn-depth interviews were conducted with 48 participants enrolled in the HTTT program. Purposive sampling was used to obtain experiences from diverse backgrounds. Content analysis was used to extract the final coding scheme.ResultsInterviewees reported a range of experiences, from positive to negative. Many of them were satisfied with efficient communication with telehealth providers, timely and convenient access to resources, and a seamless transition from enrollment to prescription. However, some interviewees noted limited interactions with telehealth providers, delayed access to treatment and cost challenges, and navigation and coordination challenges. For a future home-based Teat to Treat program, interviewees recommended improving inclusivity, offering more comprehensive consultation, enhancing user-friendliness, and increasing awareness through diverse platformsDiscussionThis study highlights a home-based Test to Treat program as a feasible way to improve access to COVID-19 and influenza care. Enhancing interactions with providers, comprehensive care, and support for marginalized populations may further expand the program and reduce disparities in access to tests and treatments.

Avian influenza virus cross-species infection in humans poses a major threat to global public health. Species-specific differences between avian ANP32A and mammalian ANP32 proteins create a natural barrier against viral cross-species infection by directly impairing the functional interaction between the avian-origin viral RNA polymerase and mammalian ANP32 proteins, thereby restricting viral genome replication. The key to overcoming this barrier lies in the adaptation of viral RNA polymerase to host ANP32 family proteins. This mini-review summarizes the mechanisms and variations in influenza virus adaptation to ANP32 proteins across different species. Influenza viruses adapt to species-specific ANP32 proteins through various mutations and display distinct preferences for specific ANP32 family members within the same host. Additionally, alternative splicing variants of ANP32A within a single species further modulate viral RNA polymerase adaptability. Despite this diversity, the underlying interaction mechanism remains conserved: ANP32-polymerase binding is necessary but not sufficient for optimal polymerase activity. This interaction facilitates the formation of asymmetric polymerase dimers and specifically supports viral genome replication, while the step from cRNA to vRNA remains subject to species-specific restrictions. This explains the classic adaptive mechanism of the PB2 E627K mutation, which restores efficient viral genome replication through acid-base pairing with ANP32A. Furthermore, adaptive mutations in emerging strains such as H3N2 canine influenza virus and recent cases of H5N1 in dairy cows underscore the need for continuous viral surveillance and deeper mechanistic studies on virus-ANP32 interactions. Such research is strategically critical for advancing the One Health approach and mitigating future influenza pandemics.

Funding the priorities of the influenza vaccines research and development roadmap: an evaluation of global investment.

Influenza's rapid evolution, driven by its segmented RNA genome, high mutation rate, and extensive animal reservoirs, underpins its capacity to cause recurring epidemics and unpredictable pandemics. Recent advances in artificial intelligence (AI) and machine learning (ML) are transforming influenza forecasting by enabling the prediction of viral evolution and the optimisation of public health preparedness. This review synthesises insights from historical data (1890-2025) and contemporary research to examine the evolving role of AI in influenza prediction. It highlights major developments including transformer-based models for viral evolution, real-time integration of mobility and environmental data, hybrid quantum, which are classical algorithms, and multimodal data fusion frameworks, it also consideres critical risk modifiers such as meteorological variation, armed conflict, and host genetics. Importantly, the review distinguishes between retrospective, proof-of-concept analyses and prospective, real-time forecasting applications, clarifying their respective contributions to operational public health preparedness and informed decision-making.

Background/Objectives: The current strategy for seasonal influenza prophylaxis relies on updating the vaccine components annually to account for the rapid antigenic drift of viruses and the low cross-protective efficacy of available vaccines. Mutant influenza viruses with truncated or deleted NS1 protein are known to stimulate cross-specific T-cell immune response and provide protection against heterosubtypic influenza A and B viruses. Methods: We generated NS1ΔC influenza A and B viruses with C-terminal NS1 deletions by reverse genetics. In a mouse model, we assessed the safety and immunogenicity of the B/Lee/NS1ΔC strain upon intranasal administration, as well as the mechanism of its cross-protective efficacy against sublethal B/Victoria and B/Yamagata challenges. We then investigated the potential of the intranasal Flu/NS1ΔC vaccine–a trivalent formulation of NS1ΔC A/H1N1, A/H3N2, and B influenza viruses–to protect mice from lethal influenza infection with homologous, heterologous, and antigenically drifted influenza A and B viruses. Results: Intranasal immunization with the B/Lee/NS1ΔC strain was safe in mice. It activated cross-specific T-cell responses in the lungs and protected animals against heterologous challenge by reducing viral load, inflammation, and lung pathology. Immunization with the trivalent Flu/NS1ΔC vaccine formulation improved survival and reduced weight loss and viral load upon challenge with A/H1N1pdm, A/H2N2, A/H5N1, and B/Victoria viruses. Conclusions: The trivalent intranasal Flu/NS1ΔC influenza vaccine is a promising tool to improve seasonal influenza protection and preparedness for an influenza pandemic.

Abstract Emerging pandemic threats and the complexity of Coronavirus Disease 2019 (COVID-19) management necessitate critical reflection on passive immunization strategies. Convalescent plasma (CP), initially considered a promising therapeutic strategy early in the SARS-CoV-2 pandemic, now occupies a narrower, albeit important, therapeutic niche within the broader treatment landscape. CP has been applied across various viral outbreaks, including viral hemorrhagic fevers such as Ebola and Argentine hemorrhagic fever, severe acute respiratory syndrome (SARS), influenza pandemics, and most recently COVID-19. Given its safety and rapid availability in the absence of specific therapies, CP represents a potentially promising option under certain conditions. Recent large-scale randomized controlled trials and meta-analyses demonstrate that early CP administration within 7 days of symptom onset significantly reduces mortality risk in hospitalized patients, particularly among immunocompromised individuals. However, late administration provides no clear mortality benefit. Recent studies have revealed that conventional plasma units exhibit neutralizing antibody levels comparable to specialized CP units, opening potential for conventional plasma as a more accessible alternative. This finding expands the practical applications of plasma-based therapies. The future clinical significance of CP depends on optimized patient selection, deeper understanding of antibody dynamics, and strategic integration into pandemic preparedness frameworks. CP remains viable for early-stage disease in immunocompromised patients and for emerging viral infections lacking specific therapeutics, including potential novel coronaviruses, henipaviruses, and arenaviruses. Continued research and technological advances in plasma processing will be essential for defining CP’s enduring role in global health security and preparedness for future high-consequence pathogens.

The 2009 pandemic H1N1 (pH1N1) influenza A virus (IAV) is a reassortant virus with two polymerase components, PA and PB2, originating from avian IAV. Avian IAV polymerase does not function efficiently in mammalian cells without host-adaptive mutations. The mechanism by which pH1N1 replicates in human hosts is not fully elucidated, as pH1N1 does not contain the host-adaptive PB2 E627K mutation required for species-specific interaction with ANP32, which facilitates replicase (polymerase oligomer) formation. Our previous research revealed that mutations in PA played a key role in mammalian host adaptation of pH1N1. These mutations were found in two separate domains of PA, the C-terminal (CTD) and N-terminal domains (NTD). We reported that the NTD mutations increase the expression of NP through enhanced association of GRSF1 with the mRNA transcripts. However, the role of CTD mutations, which are located at the interface of the polymerase oligomers, has not been elucidated. In this study, we characterized the effect of key CTD mutations and found that the CTD mutations enhanced genome replication activity and replicase formation in vitro. Unexpectedly, rescued viruses containing only the CTD mutations that enhance genome replication activity had an attenuated viral growth phenotype. However, the introduction of an additional NTD mutation to the virus restored virus growth in mammalian cells. These results suggest that the mutations found in the PA NTD are required together with CTD mutations for balanced genome replication and growth in human cells.IMPORTANCEThe 2009 pandemic H1N1 (pH1N1) influenza A virus (IAV) is a reassortant virus with two polymerase components, PA and PB2, originating from avian IAV, which typically does not function well in mammalian cells. All the human IAVs, except pH1N1, contain E627K in the PB2 subunit, which allows the virus to utilize host factor ANP32 to form polymerase oligomers required for genome replication. The mechanism of how pH1N1 adapted to humans and caused seasonal epidemics is not yet fully elucidated, but our previous studies revealed that mutations in PA play a key role in host adaptation. Here, we describe a novel mechanism of host adaptation where mutations in the PA CTD enhance genome replication, whereas PA NTD mutations increase nucleoprotein production to support increased replication activity. This finding highlights the range of mechanisms of host adaptation, which is vital to understanding when assessing the potential emergence of novel viruses.

Influenza A virus (IAV) causes annual epidemics and sporadic pandemics of acute respiratory infections resulting in significant morbidity and mortality. Although approved influenza antivirals (e.g., oseltamivir and baloxavir) exist, concerns persist about the potential for emergence of drug-resistant variants, highlighting the continuing need for new antiviral therapies. Here, we describe the development of an orally bioavailable, direct-acting antiviral (VNT-101) with a novel mechanism of action: disrupting homo-oligomerization of the influenza nucleoprotein (NP) and thereby inhibiting viral RNA synthesis. Selection of drug-resistant mutants revealed amino acid substitutions mapping to the oligomerization domain of NP, and X-ray crystallography co-structure determination of VNT-101 complexed with recombinant NP confirmed VNT-101 binding in the oligomerization pocket. Biochemical experiments using size exclusion chromatography confirmed disruption of oligomerization when this chemotype is added to preparations of recombinant NP in vitro. VNT-101 has potent and specific activity against the currently circulating IAV subtypes H1N1 and H3N2, with mean EC50 values ranging from 2 to 18 nM, and displays strong efficacy in a murine model of lethal influenza infection when administered either prophylactically or therapeutically. Importantly, VNT-101 remains active against influenza variants that are resistant to either oseltamivir or baloxavir and also has potent activity against highly pathogenic avian H5N1 and H7N9 isolates that have transmitted to humans and represent strains of potential pandemic concern. These studies support the continued development of VNT-101 to augment our therapeutic arsenal against both seasonal and pandemic influenza.

Following the 2009 H1N1 influenza pandemic, the World Health Organization (WHO) established a new case definition for severe acute respiratory infection (SARI) for viral surveillance. Several studies have suggested that SARI case definitions are inaccurate at detecting pediatric disease burden. Understanding the performance of SARI case definitions in children is important for pandemic preparedness. To evaluate the diagnostic accuracy of SARI case definitions in detecting microbiologically confirmed viral respiratory tract infections among hospitalized children. The MEDLINE(R), Embase Classic + Embase, Ovid EBM Reviews Cochrane Central Register of Controlled Trials, Elsevier SCOPUS, and the WHO Global Index Medicus databases were searched from inception to March 31, 2025. Study screening was conducted in duplicate by 2 independent reviewers. Any studies that assessed any SARI definition in hospitalized children were included. There were no restrictions by design, time period, or geographical location. Data extraction using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline was conducted by 1 author using a predefined template and independently validated by a second author. Diagnostic accuracy was extracted as 2 × 2 tables from each study and pooled using a bivariate random-effects model. Quality assessments were conducted using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The primary outcomes were sensitivity and specificity. For each case definition-virus combination with at least 4 included studies, pooled estimates of sensitivity and specificity were calculated. Of 1144 studies identified, 13 were included. Included studies represent surveillance data from 65 inpatient sites across 8 countries, using data from 2007 to 2023. The most common definition was the 2014 WHO SARI (9 studies). Viral pathogens included influenza (10 studies) and respiratory syncytial virus (RSV; 6 studies). Meta-analysis of the WHO 2014 SARI definition yielded a sensitivity of 75.7% (95% CI, 65.0%-83.9%; I2 = 89.2%) and specificity of 30.6% (95% CI, 19.8%-44.0%; I2 = 99.0%) for influenza (7 studies) and sensitivity of 70.6% (95% CI, 56.9%-81.9%; I2 = 98.8%) and specificity of 38.7% (95% CI, 25.7%-53.5%; I2 = 99.5%) for RSV (5 studies). In younger subgroups, sensitivity appeared to decrease while specificity appeared to increase for both influenza and RSV. In this systematic review and meta-analysis of 13 studies, the WHO 2014 SARI definition demonstrated reduced sensitivity and increased specificity in younger pediatric cohorts, suggesting that surveillance systems that rely on SARI case definitions may potentially underestimate disease burden in children.

H5N1 is a highly pathogenic avian influenza virus of major global concern. Since 2023, it has circulated widely among wild and farmed birds, with increasing spillover into mammals, including minks, seals, and cattle, and sporadic infections in humans in Chile, the UK, and the USA. The risk of a future pandemic is considered high because ongoing viral evolution could enable efficient human-to-human transmission. The hemagglutinin (HA) glycoprotein is the principal determinant of host range, mediating viral attachment and entry through interactions with sialylated glycans and potentially additional host surface proteins. Here, we developed an artificial intelligence (AI)-based pipeline integrating structural modeling, protein–protein interaction prediction, and biological filtering to identify human cell surface proteins with high likelihood of interacting with H5N1 HA. These interactions may contribute to viral entry and tropism and therefore represent promising candidates for experimental validation and therapeutic targeting. Our findings highlight the utility of AI-driven pipelines in accelerating the discovery of host factors relevant to pandemic influenza viruses.

IntroductionThe loss of 50,000,000 people during the 1918 influenza pandemic was blamed on war, unsanitary conditions, and lack of vaccines and preparation. Nine decades later, a similar virus (H1N1) killed 285,000 people, and again, the response was that preparation was ineffective, inefficient, and inequitable. Less than a decade later, preparedness for the coronavirus disease 2019 (COVID-19) outbreak revealed the United States was not prepared.This study’s objectives were: 1) to develop a deeper understanding of leadership practices that led to successful responses to the COVID-19 pandemic, and 2) to learn about the underlying principles and practices that may help in preparing for the next pandemic.MethodsSenior leaders (14/23 or 61%) from across a multisite, multicountry integrated health system were recruited using maximum variation sampling. Individual recorded interviews (averaging 20 minutes) were based on principles of Appreciative Inquiry and critical incident reporting. Iterative consensus coding produced 6 major themes: self- and situation awareness, teamwork, readiness, inspirational leadership, internal communication, and external communication.ResultsBeyond individual leadership decisions, organizational culture, shared cognition, and history may play a major role in shaping system-wide responses to catastrophic events like the COVID-19 pandemic.DiscussionLack of preparation for dealing with novel events and one-way communication may be risk factors for chaotic and ineffective responses.ConclusionSenior leaders must balance clinical necessity with humanistic values and purpose. Situation awareness and attention to organizational culture may improve the quality, timeliness, and effectiveness of responses to the next pandemic threat.

An increase in the number of human cases of influenza A/H5N1 infection in the USA has raised concerns about the pandemic potential of the virus. Pre-existing population immunity is a key determinant for risk assessment and pandemic potential for any virus. Antibody responses against the bovine A/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins were measured among a population of influenza-vaccinated or influenza-infected individuals. Modest titers of bovine A/H5N1 HA-binding antibodies and low to undetectable neutralizing antibody titers were detected in a cohort of 73 individuals. Conversely, bovine A/H5N1 NA-binding and neuraminidase-inhibiting antibody titers were comparable to those against a human A/H1N1 NA at baseline. Seasonal influenza vaccination failed to significantly increase antibody titers against both HA and NA glycoproteins of bovine A/H5N1. Recent infection with human A/H1N1 but not A/H3N2 viruses induced significant increases in bovine A/H5N1-neutralizing antibody, as well as increases in NA-binding and NA-inhibiting antibodies to bovine A/H5N1 NA. While the degree of protection afforded by these A/H5N1 cross-reactive antibodies is not known, incorporating NA or enhancing current seasonal vaccine formulations to increase NA-specific antibody titers may increase antibody breadth and protection against both seasonal and pandemic influenza viruses.IMPORTANCEA/H5N1 influenza A viruses continue to pose a pandemic threat to humans. Recent infection of dairy cattle and poultry with A/H5N1 in the USA has magnified that concern. We determined the level of antibodies that recognize A/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins in a population in Baltimore, MD. We show that while low levels of H5 HA-binding and A/H5N1-neutralizing antibodies are present, there is a significantly stronger recognition of bovine N1 NA. Vaccines that target the N1 NA protein may induce protective antibody responses in humans due to the presence of cross-reactive human N1 NA antibodies.

Pandemic Spanish influenza of 1918–19 in India with special reference to colonial Bengal: A historical perspective

We continue to struggle with the prevention and treatment of the influenza virus. The 2009 swine flu pandemic, caused by the H1N1 strain of influenza A, resulted in numerous fatalities. The threat of influenza remains a significant concern for global health, and the development of novel drugs targeting these viruses is highly desirable. The objective of this study is to explore the inhibitory potential of terpenoid compounds against the Nucleoprotein (NP) of influenza A virus, which is a highly effective drug target due to its ability to facilitate the transcription and replication of viral RNA. In silico research was performed to identify potential inhibitors of NP. Molecular docking studies were conducted to assess the binding of terpenoid compounds to the active site residues of the target protein. The most promising hits were then subjected to molecular dynamics simulations to examine the stability of the protein-ligand complexes. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) studies and Lipinski's rule of five were employed to evaluate the drug safety and druglikeness of the compounds. Docking studies revealed that the terpenoid compounds bind strongly to the active site residues of the NP protein. Molecular dynamics simulations demonstrated the stability of the proteinligand complexes for the best-hit compounds. ADMET studies and Lipinski's filter indicated that the compounds exhibit desirable drug safety and drug-likeness profiles. This work may contribute significantly to drug discovery and the development of therapeutic agents against the influenza A virus. The identification of terpenoid compounds that bind strongly to the NP protein and exhibit favorable drug-like properties through in silico studies provides a promising foundation for further research and the development of potential inhibitors targeting this critical viral protein.