Chikungunya virus vaccine (Valneva)

Total product sales of €30.5 million Cash position of €105.3 million as of end March 2026, excluding proceeds from successful reserved offering completed in April 2026 1 Program launched in April to further reduce operating expenses Pfizer expected to submissions for Lyme disease vaccine candidate Lyon (France), May 13, 2026 – Valneva SE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, today reported its financial results for the first quarter ended March 31, 2026, provided key corporate updates, and updated its 2026 financial guidance. The condensed consolidated interim financial results are available on the Company’s website ( Financial Reports – Valneva ). Valneva will provide a live webcast of its first quarter 2026 results conference call beginning at 3 p.m. CEST/9 a.m. EDT today. This webcast will also be available on the Company’s website. Please refer to this link: First quarter 2026 Financial Update Total revenues were €30.9 million, including €30.5 million in product sales, compared with €49.2 million and €48.6 million, respectively, in the first quarter of 2025, mainly reflecting the planned wind-down of third-party sales (-97.6% versus the first quarter of 2025) and a different shipment phasing to the U.S. Department of Defense Operating cash burn continued to decline, improving to €0.3 million in the first quarter of 2026, compared to €8.1 million in the first quarter of 2025 Cash position of €105.3 million as of March 31, 2026, compared to €109.7 million as of December 31, 2025 Excludes €37.0 million in gross proceeds from recent successful reserved offering 1 Net loss of €32.1 million, compared with a net loss of €9.2 million in the first quarter of 2025 mainly impacted by one-off effects in cost of goods (termination of contracts, standard cost adjustment, inventory write-offs), in addition to idle cost and lower sales. Financial Outlook Valneva is adjusting its 2026 sales and revenue guidance partially as a result of an emerging adverse trend in travel vaccine uptake across key markets, driven by geopolitical factors. The Company is therefore revising its product sales guidance to €135 million to €150 million from €145 million to €160 million previously Other revenues are reconfirmed – resulting in a new total revenue guidance of €145 million to €160 million As part of the Company’s continued focus on diligent cash management, and following the recent consolidation in France 2 , Valneva has initiated a further restructuring plan designed to streamline its global business operations: Focus resources on its base business and key strategic projects, including a reduction of its global workforce by 10-15% Together these initiatives are expected to result in significant ~25-35% reduction in 2026 operating expenses compared to 2025 Product gross margins are expected to normalize following one-off effects in the first quarter of 2026 Peter Bühler, Valneva’s Chief Financial Officer, commented, “Our first‑quarter sales reflect the sharp decline in third party products and our planned focus on proprietary products. We also see the first indications of the geopolitical situation adversely affecting travel. We continued to reduce our operating cash burn meaningfully and, combined with further cost saving measures and our strengthened balance sheet following the successful financing completed in April, we expect a solid cash position through the potential regulatory approvals of our Lyme disease vaccine.” Financial Information (Unaudited results, consolidated per IFRS) € in million Three months ended March 31 2026 2025 Total Revenues 30.9 49.2 Product Sales 30.5 48.6 Net loss (32.1) (9.2) Adjusted EBITDA (18.2) (0.6) Cash 105.3 153.0 Commercial Portfolio Valneva’s commercial portfolio comprises three vaccines: IXIARO ® /JESPECT ® , DUKORAL ® and IXCHIQ ® . The Company’s main third‑party product distribution contract concluded in 2025 and, as previously communicated, this activity is now intentionally winding down. As a result, third‑party product sales were reduced by 97.6% in the first quarter of 2026 to €0.1 million. This strategic initiative is expected to result in improved overall product gross margins. JAPANESE ENCEPHALITIS VACCINE IXIARO ® /JESPECT ® In the first quarter of 2026, IXIARO ® /JESPECT ® sales were €20.2 million, compared with €27.5 million in the first quarter of 2025. The year‑over‑year decline primarily reflects a difference in the phasing of deliveries to the U.S. Department of Defense (DoD). Deliveries have continued under the current contract signed in January 2025, and Valneva expects to deliver further IXIARO ® doses to the DoD in 2026. CHOLERA / ETEC 3 -DIARRHEA VACCINE DUKORAL ® In the first quarter of 2026, DUKORAL ® sales reached €8.6 million versus €12.3 million in the first quarter of 2025, which included one-off sales related to the supply of doses to Mayotte following a cholera outbreak. First quarter 2026 sales were adversely impacted by the distributor transition in Germany in January 2026, as residual supply transferred from the previous distributor was sufficient to satisfy the demand for this quarter. Product deliveries are expected to resume in the second quarter of 2026. CHIKUNGUNYA VACCINE IXCHIQ ® In the first quarter of 2026, IXCHIQ ® sales amounted to €1.6 million, compared with €3.0 million in the first quarter of 2025, which had benefited from sales in the United States and shipments of doses to the French island of La Réunion following a chikungunya outbreak. Clinical Stage Programs LYME DISEASE VACCINE CANDIDATE – LB6V (formerly VLA15) Regulatory submissions expected In March 2026, Valneva and Pfizer announced topline results from the Phase 3 VALOR “Vaccine Against Lyme for Outdoor Recreationists” clinical trial ( NCT05477524 ) of their investigational six valent OspA-based Lyme disease vaccine candidate LB6V 4 . LB6V demonstrated more than 70% efficacy in preventing Lyme disease in individuals aged five years and above. The investigational vaccine candidate was well tolerated with no safety concerns identified. Overall, results strengthen confidence in the vaccine candidate and Pfizer is planning submissions to regulatory authorities. VLA15 is the only Lyme disease program in late-stage clinical development today and has received Fast Track designation from the U.S. Food and Drug Administration (FDA). CHIKUNGUNYA VACCINE - IXCHIQ ® / VLA1553 Pilot vaccination campaign ongoing in Brazil In February 2026, Valneva and Instituto Butantan announced the initiation of a Pilot Vaccination Strategy (PVS) in Brazil using Valneva’s single-shot chikungunya vaccine, IXCHIQ ® . The vaccination campaign will serve as the basis for post-marketing commitments. To date, over 30,000 adults, aged 18 to 59 years, have already been vaccinated as part of this campaign which evaluates the effectiveness and safety of IXCHIQ ® in a real-world setting. In early May 2026, the Brazilian Health Regulatory Agency (ANVISA) authorized Instituto Butantan to locally manufacture a version of Valneva’s chikungunya vaccine 5 . With this authorization, the vaccine – developed in partnership with Valneva and supported by the Coalition for Epidemic Preparedness Innovations (CEPI) – is approved for use in Brazil in individuals aged 18 to 59 and can be incorporated into the Unified Health System. SHIGELLA VACCINE CANDIDATE – S4V2 First Phase 2 results expected mid-2026 S4V2 is the world’s most clinically advanced tetravalent vaccine candidate against shigellosis, the second leading cause of fatal diarrhea worldwide. Two clinical trials of S4V2, a Phase 2 infant safety and immunogenicity trial 6 , and a Phase 2b Human Challenge trial (CHIM) 7 , sponsored by LimmaTech Biologics AG, are ongoing. First Phase 2 results are expected mid-2026. Subject to positive results for both trials, Valneva will assume responsibility for all further development 8 . No approved multivalent Shigella vaccine is currently available outside of Russia or China, and the development of Shigella vaccines has been identified as a priority by the World Health Organization (WHO) 9 . In October 2024, the U.S. FDA granted Fast Track designation to S4V2, recognizing its potential to address a serious condition and fill an unmet medical need 10 . The global market opportunity for a vaccine against Shigella is estimated to exceed $500 million annually 11 . First Quarter 2026 Financial Review (Unaudited, consolidated under IFRS) Revenues Valneva’s total revenues were €30.9 million in the three months ended March 31, 2026 compared to €49.2 million for the same period in 2025. The decrease was primarily attributable to the discontinuation of third-party product distribution, differences in the schedule of shipments to the U.S. Department of Defense, the distributor transition in Germany, as well as one off outbreak-related sales of DUKORAL ® and IXCHIQ ® in 2025 that did not recur in 2026. Other revenues, including revenues from collaborations, licensing and services remained largely unchanged and amounted to €0.4 million in the three months ended March 31, 2026 compared to €0.6 million for the same period in 2025. Operating Result and adjusted EBITDA Costs of goods and services sold (COGS) were €26.2 million for the three months ended March 31, 2026. The gross margin on commercial product sales, excluding IXCHIQ ® , was 45.1% compared to 62.7% for the three months ended March 31, 2025. The positive impact of lower third-party product sales was offset by higher manufacturing expenses following the transfer of manufacturing to the new Almeida facility in Scotland, and by additional one-time effects. Gross margin for IXIARO ® was 50.8% compared to an exceptionally high 72.6% achieved in the first quarter of 2025 (full-year 2025 IXIARO ® gross margin of 59.6%). The decline was primarily driven by higher manufacturing costs at the Almeida facility, increased batch write-offs, and lower sales volumes. Gross margin for DUKORAL ® reached 33.6% compared to 52.2% in the first quarter of 2025, with the decline primarily attributable to batch write-offs. Gross margin for IXCHIQ ® was negative, mostly impacted by cancellation fees related to external manufacturing commitments following lower than anticipated sales. Additionally, COGS included €0.2 million attributable to the third-party distribution business, €5.0 million related to idle capacity and costs not allocated to products, and €0.3 million related to services. By comparison, total COGS in the first quarter of 2025 were €23.0 million, comprising €21.3 million of cost of goods and €1.8 million of cost of services. Research and development expenses remained stable at €15.2 million for the three months ended March 31, 2026. Marketing and distribution expenses totaled €7.0 million in the first three months of 2026, down from €10.4 million in the first three months of 2025. The decrease primarily reflects lower advertising and promotional spending related to IXCHIQ ® as well as overall lower personnel costs and reduced warehousing and distribution expenses. General and administrative expenses decreased to €8.2 million in the three months ended March 31, 2026, from €9.0 million in the same period of 2025. The reduction was primarily driven by lower personnel costs and savings in advisory and professional services. Other income, net of other expenses, decreased to €1.9 million in the three months ended March 31, 2026, from €2.2 million in the three months ended March 31, 2025. Lower R&D tax credits were partially offset by higher grant income. Valneva recorded an operating loss of €23.7 million for the three months ended March 31, 2026 compared with an operating loss of €6.0 million in the same period in 2025. The increase in operating loss was mainly driven by lower product sales in the first three months of 2026, compared to the prior-year period. Adjusted EBITDA loss (as defined below) was €18.2 million in the three months ended March 31, 2026, compared with an adjusted EBITDA loss of €0.6 million in the corresponding period of 2025. Net Result In the three months ended March 31, 2026, Valneva generated a net loss of €32.1 million, compared to a net loss of €9.2 million in the first three months of 2025. The increase in net loss was primarily driven by lower sales in the first three months of 2026. Finance expense and currency effects resulted in a net finance expense of €7.6 million in the first three months of 2026, compared with a net finance expense of €1.8 million in the first three months of 2025. The increase was mainly attributable to unfavorable movements in the USD/EUR exchange rate, which led to a foreign currency loss of €3.0 million in the first quarter of 2026, compared with a foreign currency gain of €3.7 million in the first quarter of 2025. Cash Flow and Liquidity Net cash used in operating activities amounted to €0.3 million in the three months ended March 31, 2026 compared to €8.1 million in the same period of 2025. The reduction in the first quarter of 2026 was primarily driven by lower net working capital requirements. Cash inflows from investing activities amounted to €0.3 million in the three months ended March 31, 2026 compared to cash outflows of €1.0 million in the three months ended March 31, 2025. Cash inflows in the first quarter of 2026 were largely attributable to proceeds from the investment of liquidity into money market funds. Cash outflows in the first quarter of 2025 were mainly related to the purchase of equipment, partially offset by interest proceeds. Net cash used in financing activities amounted to €4.7 million in the three months ended March 31, 2026 compared to a net cash outflow of €5.6 million in the same period in 2025. Cash outflows in both periods primarily reflected interest and lease payments. Cash and cash equivalents were €105.3 million as at March 31, 2026, compared to €109.7 million at December 31, 2025. Non-IFRS Financial Measures Management uses and presents IFRS results alongside the non-IFRS measure of Adjusted EBITDA to evaluate and communicate its performance. While non-IFRS measures should not be construed as alternatives to IFRS measures, management believes they provide useful additional insight into Valneva’s current performance, performance trends, and financial condition. Adjusted EBITDA is a common supplemental performance measure among investors and financial analysts. Management believes this measure provides additional analytical tools. Adjusted EBITDA is defined as earnings / (loss) for the period before income tax, finance (income)/expense, foreign exchange (gain)/loss, amortization, depreciation, and impairment. A reconciliation of Adjusted EBITDA to net loss for the period, which is the most directly comparable IFRS measure, is set forth below: € in million Three months ending March 31 (consolidated per IFRS) 2026 2025 Profit/(Loss) for the period (32.1) (9.2) Add: Income tax expense 0.8 1.5 Total Finance income (0.5) (0.5) Total Finance expense 5.1 6.0 Foreign currency (gain)/loss – net 3.0 (3.7) Amortization 1.2 1.2 Depreciation 4.2 4.2 Adjusted EBITDA (18.2) (0.6) Product sales at constant exchange rates: References to changes in net sales at constant exchange rates (CER) indicate that currency fluctuation effects have been removed. Net sales for the period in question are recalculated using the exchange rates applied in the prior period, as detailed below: € in million Three months ended March 31 (unaudited results, consolidated per IFRS) 2026 2025 Product sales 30.5 48.6 Third-party product sales 0.1 5.8 Product sales excluding third-party sales 30.4 42.8 Effect of exchange rates (excluding third-party sales) 1.3 Product sales (excluding third-party sales) at constant exchange rates (CER) 31.7 About Valneva SE We are a specialty vaccine company that develops, manufactures, and commercializes prophylactic vaccines for infectious diseases addressing unmet medical needs. We take a highly specialized and targeted approach, applying our deep expertise across multiple vaccine modalities, focused on providing either first-, best- or only-in-class vaccine solutions. We have a strong track record, having advanced multiple vaccines from early R&D to approvals, and currently market three proprietary travel vaccines. Revenues from our growing commercial business help fuel the continued advancement of our vaccine pipeline. This includes the only Lyme disease vaccine candidate in advanced clinical development, which is partnered with Pfizer, the world’s most clinically advanced Shigella vaccine candidate, as well as vaccine candidates against other global public health threats. More information is available at . Valneva Investor and Media Contacts Laetitia Bachelot-Fontaine VP, Global Communications and European Investor Relations M +33 (0)6 4516 7099 laetitia.bachelotfontaine@valneva.com Joshua Drumm, Ph.D. VP, Global Investor Relations M +001 917 815 4520 joshua.drumm@valneva.com Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 and securities laws in France. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. All statements other than statements of historical facts contained in this press release are forward-looking statements, including, but not limited to, statements with respect to: future financial performance and financial guidance including projected product sales, total revenue and total R&D investments; Valneva’s plans for investment in future growth; the timing of orders for commercial products; plans and expectations regarding the development, commercialization and commercial prospects of Valneva’s product candidates and commercial products, including the prospects and timing of actions relating to clinical studies and trials and product approvals, such as study initiations, study advancements, data readouts, submissions, filings, approvals, and label expansions; the expected benefits and availability of Valneva’s commercial products and product candidates; and potential growth opportunities and trends, including the assumptions and expectations regarding total market opportunity targeted by Valneva’s product candidates and commercial products. These forward-looking statements are based on Valneva’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause Valneva’s business, strategy, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Many factors may cause differences between current expectations and actual results, including: Valneva’s success in the commercialization of its commercial products; uncertainties and delays involved in the development and manufacture of vaccines; the potential that success in preclinical testing and earlier clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate; the impacts of macroeconomic conditions, including tariffs and other trade policies, the conflict in Ukraine and the conflict in the Middle East, fluctuations in inflation and uncertain credit and financial markets, on Valneva’s business, clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; Valneva’s ability to realize the benefits of its collaboration and license agreements; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; the impact of the global and European credit crisis; the ability to obtain or maintain patent or other proprietary intellectual property protection and unexpected litigation or other disputes. Other factors that may cause the Company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified in the section titled “Risk Factors” in Valneva’s Annual Report on Form 20-F for the year ended December 31, 2025 filed with the U.S. Securities and Exchange Commission (“SEC”) and the Autorité des marchés financiers (“AMF”) on March 18, 2026, and in other filings made with the SEC and AMF from time to time. Valneva is providing this information as of the date of this press release and expressly disclaims any intention or obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by law. 1 2026_04_30_Financing_PR_EN_Final.pdf 2 Valneva to Further Consolidate its Operations in France - Valneva 3 Indications differ by country - Please refer to Product / Prescribing Information (PI) / Medication Guide approved in your respective countries for complete information, incl. dosing, safety and age groups in which this vaccine is licensed, ETEC = Enterotoxigenic Escherichia coli (E. Coli) bacterium. 4 2026_03_23_Lyme-Phase-3-Data-Read-out_PR_EN_FINAL.pdf 5 6 Valneva and LimmaTech Announce First Vaccination in Phase 2 Infant Study of Tetravalent Shigella Vaccine Candidate S4V2 - Valneva 7 Valneva and LimmaTech Announce First Vaccination in Phase 2b Human Challenge Study of Tetravalent Shigella Vaccine Candidate S4V2 8 Valneva and LimmaTech Enter into a Strategic Partnership to Accelerate the Development of the World’s Most Clinically Advanced Tetravalent Shigella Vaccine Candidate - Valneva 9 Immunization, Vaccines and Biologicals (who.int) 10 Valneva and LimmaTech Awarded FDA Fast Track Designation for Tetravalent Shigella Vaccine Candidate S4V - Valneva 11 LEK analysis Attachment 2026_05_13_Q1_Results_PR_EN_Final

基孔肯雅热是一种由基孔肯雅病毒引起的蚊媒传染病，其临床表现主要包括发热、皮疹和关节肌肉疼痛，部分患者甚至发展为持续半年以上的慢性多发性关节炎[1]。随着全球变暖及病毒适应性的增强，该病的暴发频率和传播范围不断扩大，已由亚非地区蔓延至全球110多个国家并成为热带和亚热带地区的重要公共卫生问题[2]。我国自2008年在广东口岸检出首例输入病例以来，多地相继报告输入病例并发生本地流行[3]。2025年7月广东佛山再次报告基孔肯雅热病例，1个月内累计逾数千例[4]，提示该病在中国仍存在一定的公共卫生风险。目前临床治疗以对症支持为主，主要依靠退烧和抗炎药物缓解症状[5-6]，尽管抗病毒治疗被视为关键途径，但全球至今仍无获批的特效药物[7]。生物药与疫苗被认为是重要的防控手段[8]，美国和加拿大先后获批的减毒活疫苗IXCHIQ已上市[9]，而中国尚无相关疫苗获批。 在此背景下，系统梳理基孔肯雅热抗病毒研究的进展与不足具有重要意义。一方面，文献计量学通过定量分析发文量、国家、机构、作者、期刊及关键词以揭示全球研究格局和核心力量分布，从而识别该领域的重点方向与前沿动态[10]；另一方面，对抗病毒药物相关研究的分析有助于明确药物研发热点与潜在突破口，为候选药物筛选加速、中西医结合研究深化及临床转化推进提供科学依据。然而，目前尚缺乏针对基孔肯雅热抗病毒治疗的系统文献计量学研究，阶段性成果的总结亦相对不足。因此，本研究系统梳理2004—2025年相关研究，采用文献计量学与可视化方法揭示该领域的研究现状与热点趋势，以期为感染防控与抗病毒药物研发提供参考。 1 材料和方法 1.1  数据来源和检索策略 检索开源科学引文索引数据库Web of Science（WOS，https://www. webofscience.com/wos/）的核心合集，采用高级检索方式，以“疾病”和“抗病毒研究”为主题词构建检索式：chikungunya OR CHIKV (Title) AND antiviral (Topic)*，检索时间范围设定为平台建库至2025年8月10日，文献类型限定为“Article”和“Review Article”，语种限定为英文，排除会议摘要、总结报告等无效文献。经数据清洗与标准化处理后将文献导出为RefWorks格式。 1.2  数据处理与分析 使用VOSviewer 1.6.18对年度发文量、发文国家、机构、作者及关键词进行统计与可视化分析，参数设置如下：国家合作网络图中最小词频阈值设定为1；作者合作网络图中最小词频阈值设定为5；其余参数均使用默认值。依据普赖斯定律M＝0.749（Nmax为最高产作者的发文量，M为核心作者的最低论文数）来界定核心作者[11]。在国家合作网络图中，节点越大表示国家发文量越高，节点间连线越粗表示国家间合作越紧密；在核心作者合作网络图中，颜色越深代表作者影响力越高。 使用CiteSpace 6.3.R3对关键词进行统计分析，绘制关键词共现、时间线和突现图谱。参数设置如下：时间跨度为2004年1月—2025年8月，时间切片为1年；数据抽取阈值采用G-index算法，K值设定为20；网络裁剪方法使用pathfinder算法；其余参数使用默认值。关键词共现网络图中，节点越大表示关键词出现频次越高，节点间连线越粗表示关键词联系越紧密。在聚类网络图中，当聚类模块值（Q）大于0.3且平均轮廓值（S）超过0.5时，聚类结果被认为具有合理性[12]。时间线图谱中，关键词标签按照首次出现的时间由左至右排序。突现图谱中设置强度阈值（γ）为0.5以平衡突现词数量与强度。 完成上述分析后，进一步使用Excel 2019对发文数量、国家、期刊、机构、作者及关键词进行统计，归纳与抗病毒药物相关的关键词并计算其出现频次，最终绘制相关图表。 2  结果 2.1 检索结果和发文趋势 纳入文献583篇，其中论著507篇、综述76篇。2004—2025年基孔肯雅热抗病毒治疗研究发文量整体呈上升趋势，2004—2013年发文量较低，2014—2015年显著增加，2016年后持续波动上升并在2022年达到峰值。虽然近3年发文量有所降低，但从整体趋势角度可以预测未来关于基孔肯雅热抗病毒药物治疗的文献数量将会继续增长（图1）。 2.2 发文国家、作者、机构和期刊分析 2.2.1  国家分析  共纳入65个国家，发文量排名前3的国家为美国（147篇）、印度（135篇）和法国（91篇）；链接强度排名前3的国家为美国（132）、法国（113）和比利时（65）。中国发文量44篇，位列第5；链接强度23，位列第13（图2）。从区域分布来看，美洲和欧洲是当前研究的核心区域，其中美国、法国、比利时和爱沙尼亚已形成较为紧密的合作网络；在亚洲，印度是主要贡献国，新加坡和中国的研究活动亦较为活跃，但整体合作程度仍逊于欧美国家。 2.2.2  作者分析  共纳入3 035名作者，发文量排名前3的作者为Merits Andres（37篇）、Neyts Johan（29篇）和Delang Leen（27篇）；总被引次数排名前3的作者为Merits Andres（2 118次）、Ng Lisa F. P.（1 183次）和Neyts Johan（1 139次）；链接强度排名前3的作者为Dash Paban Kumar（109）、Ho Yijung（95）和Zandi Keivan（89）（图3）。该领域已形成以Merits Andres和Neyts Johan为核心的2个较大合作团队，团队内部联系较为紧密，但团队之间的合作并不突出。总体来看，核心作者分布仍较为分散，尚未形成规模化的合作集群，表明该领域作者间的协作水平仍有提升空间，需要进一步加强跨区域与跨机构的合作。 2.2.3  期刊分析对相关研究期刊的统计分析有助于识别该领域的重要学术载体，为研究者在期刊选择和文献研究方面提供参考。分析结果（表1）显示，基孔肯雅热抗病毒治疗相关文献分布于211种期刊，发文量在1～43篇，其中Antiviral Research以43篇居首；Journal of Virology和PLoS Neglected Tropical Diseases分别代表病毒学和热带病研究的核心期刊，体现了该主题与病毒学基础研究及公共卫生防控之间的紧密联系；Scientific Reports和PLoS One作为综合性期刊，在该领域亦保持较高的发文量。从影响力来看，Antiviral Research、Journal of Virology和PLoS Pathogens的篇均被引频次较高，显示其在学术界被认可度和权威性。总体而言，该领域高影响力期刊主要集中于病毒学、传染病学和药物学方向，突显研究的学科聚焦性与专业属性。 2.2.4  机构分析  共纳入210个研究机构，发文量在1～37篇，排名前3的机构为塔尔图大学（University of Tartu，37篇）、巴斯德研究所（Institut Pasteur，30篇）和新加坡国立大学（National University of Singapore，27篇）；链接强度前3的机构是塔尔图大学（62篇）、巴斯德研究所（37篇）、新加坡科学技术研究局（Agency for Science, Technology and Research，34篇）；总被引频次前3的是塔尔图大学、巴斯德研究所、德克萨斯大学医学分部（University of Texas Medical Branch），分别为2 118、1 948、1 746次。德克萨斯大学医学分部篇均被引次数最高，达134次，共发表13篇文献。整体来看，该领域的高产与高影响力机构主要集中在欧美及亚洲的科研型大学和专业研究机构（表2）。 2.3  关键词分析 2.3.1 关键词共现  共纳入关键词458个，频次排名前3的高频词为“chikungunya virus”（207次）、“replication”（137次）和“infection”（128次）；链接总强度前3的关键词为“outbreak”（1 500）、“infection”（1 429）和“chikungunya”（1 257）。关键词主要聚焦于基孔肯雅病毒的复制、感染与鉴定，涉及分子对接、基因表达、抑制剂筛选等抗病毒研究以及动物模型与交叉病毒研究（图4）。 2.3.2  关键词聚类  关键词聚类中Q＝0.375 4（＞0.3）、S＝0.648 5（＞0.5），表明该聚类结果合理。如图5所示，#0 mouse model（小鼠模型）代表抗病毒研究中药效验证的核心实验模型，常与#4 protein（蛋白质）和#5 replication（复制）等机制研究相关联；#1 molecular docking（分子对接）聚焦于基于结构的药物筛选与优化，是候选抗病毒药物开发的重要技术手段；#2 sindbis virus（辛德毕斯病毒）与#3 chikungunya virus（基孔肯雅病毒）涉及病原体比较和交叉感染研究；#6 chloroquine（氯喹）代表已有药物再利用的研究方向；#7 entry（入侵）与#8 cells（细胞）关注病毒入侵及细胞感染机制，支撑药物作用靶点和阻断策略的探索。 2.3.3  关键词时间线  关键词时间线图展示了2004—2025年基孔肯雅热抗病毒研究的关键词聚类及时间分布（图6）。#0 mouse model（小鼠模型）自2004年起贯穿研究始终，反映其在药效验证与机制探究中的核心地位；#1 molecular docking（分子对接）在2008年后快速发展，推动基于结构的药物筛选；#3 chikungunya virus（基孔肯雅病毒）涵盖疫苗、结构解析等关键词，表明相关应用性研究直接服务于防控策略；#5 replication（复制）涵盖完整核苷酸序列、半胱氨酸蛋白酶、荧光共振能量转移检测等关键词，反映出针对病毒复制过程及复制相关蛋白酶功能的研究方向；#6 chloroquine（氯喹）涵盖氯喹、利巴韦林、吗替麦考酚酸和干扰素α等传统广谱抗病毒或免疫调节药物，显示2014—2018年出现了针对基孔肯雅病毒的药物再利用研究热潮。 2.3.4  关键词突现  在基孔肯雅热抗病毒治疗的研究中，关键词突现强度排名前3的是mouse model（小鼠模型）、reunion island（留尼汪岛）和epidemic（疫情爆发），突现强度分别为7.79、5.08、4.92。2004—2009年突现的epidemic（疫情爆发）和aedes albopictus（白纹伊蚊）表明早期研究多依托疫情爆发及媒介传播监测数据，为病毒传播规律解析和早期药物靶点探索奠定基础；2010—2015年突现的mouse model（小鼠模型）、E2 glycoprotein（E2糖蛋白）和monoclonal antibody（单克隆抗体）表明研究重点转向病毒结构解析及动物模型的构建与验证；2016年flavonoids（黄酮类化合物）的突现提示天然产物逐渐进入抗病毒药物筛选。此后，RNA synthesis（RNA合成）、inhibitors（抑制剂）和capsid protein（衣壳蛋白）等相继突现显示研究重点逐步转向病毒复制与抑制机制解析。Sequence（序列）、recognition（识别）和structural insights（结构解析）等关键词突现提示基因序列分析、结构生物学及识别机制研究可能成为未来趋势（图7）。 2.4  抗病毒药物类型 所纳入的文献共报道治疗药物21种，其中化学药19种，中药2种。将所有化学药按类别及出现频次进行统计后，可分为小分子抑制剂、核苷/核苷酸类似物、蛋白酶抑制剂等4类。从药物种类看，小分子抑制剂最多，共8种；从出现频次看，前5位分别为氯喹（24）、利巴韦林（9）、吗替麦考酚酸（4）、法匹拉韦T-705（2）和半胱氨酸蛋白酶（2）。目前针对基孔肯雅病毒的特效生物药研究仍不深入，中药研究频次也较低，仅有穿心莲（1）和绿茶（2）的报道（表3）。 2.5  中药、天然产物活性成分及药物发现 尽管中药在基孔肯雅热抗病毒研究中的报道数量有限，但已有部分研究将关注点延伸至植物来源的天然产物及其活性成分。通过关键词整理与归类，共纳入活性化合物4类、8种，绘制了桑基图以展示药用植物、活性成分类别以及相关药物发现（图8）。在活性成分中，黄酮类（6次，占比31.6%）和二萜类（11次，占比57.9%）出现频次较高，提示其在基孔肯雅热抗病毒研究中具有重要地位；其他关键词涉及大戟科植物、植物提取物及特定部位（如树皮）等，反映研究内容涵盖植物源筛选和成分鉴定的多个环节。 3  讨论 本研究运用文献计量学分析软件VOSviewer、CiteSpace对Web of Science核心合集中基孔肯雅热抗病毒治疗的相关文献进行系统分析，从发文数量、国家、作者、机构、期刊以及关键词等方面对该领域的研究现状、热点及趋势进行可视化展示。 3.1  发文趋势分析 研究结果表明，基孔肯雅热抗病毒研究的产出具有一定规律：一方面，重大流行事件在短期内刺激研究活跃度，导致发文量增长趋势发生变化；另一方面，技术革新、资金支持与合作网络的构建规则保障了研究的持续推进。基于此，2004—2025年该领域的学术产出整体呈现出“疫情触发-短期高峰-相对平稳”的发展特征。 3.1.1  疫情驱动下的发文量变化特征  2004—2025年研究增长的多个时间节点均与疫情的出现相关联，其中2009、2013、2019年分别是研究增长的重要节点。早期（2005—2006年）基孔肯雅热在印度洋岛屿的流行推动了传播机制和病毒进化的相关研究[13]，但受限于药物研发基础不足，整体发文量仍处于缓慢增长期；2007年在意大利的爆发[14]以及2008年中国内地首次报告输入性病例[15]后，2009年相关研究的增长速度有所增加；2013—2014年美洲和加勒比地区出现大规模流行，在前期研究基础的支撑下小分子抑制剂筛选等相关研究显著增加，发文量进入快速增长期[16]；2019年中国云南瑞丽发生局部疫情[17]，与2019—2020年的研究活跃期相对应。综合上述分析，疫情在不同阶段均对研究产出起到催化作用，提示2025年广东佛山的基孔肯雅热流行[4]或将再次引发学术关注并带动抗病毒治疗相关研究的进一步发展。 3.1.2  技术进展与资源协同成为长期支撑动力  与疫情驱动的短期波动不同，方法学进展与科研资源配置是推动基孔肯雅热抗病毒研究长期发展的核心动力。即便在无大规模暴发的年份，相关研究产出仍能维持在较高水平。一方面，高通量筛选、结构生物学和分子对接等新技术的普及，使研究团队能够在体外和计算层面快速筛选候选化合物、预测潜在作用靶点，从而显著提高研究效率[18]；另一方面，科研资金的持续投入、跨国合作网络的建设以及学术期刊对新发与再发病毒研究的关注，共同构建了稳固的研究基础。即使在新型冠状病毒肺炎（corona virus disease 2019，COVID-19）大流行期间，尽管非新型冠状病毒研究一度面临资源挤压，但跨学科研究工具的引入使包括基孔肯雅病毒在内的蚊媒病毒研究总体保持稳步上升趋势[19-20]。 3.2  基孔肯雅热抗病毒治疗研究 3.2.1  抗病毒治疗研究热点与趋势  关键词分析揭示了基孔肯雅热抗病毒研究领域的发展脉络及研究范式的演变。早期研究（2004—2009年）以“疫情爆发”“白纹伊蚊”等关键词为特征，主要集中于病毒传播规律及生态学特征的探索等方面。随着研究的深入，关注点逐渐转向病原体及其与宿主的相互作用，以“小鼠模型”为核心的体内药效评价体系、以“分子对接”为代表的计算机辅助药物设计方法以及对病毒“入侵”“复制”等生命周期环节的机制解析，形成了从体内验证、体外筛选到机制阐释的研究框架。研究趋势显示，该领域正在经历2方面的深化：其一，研究焦点正由广谱药物再利用逐步转向精准靶向探索。早期对氯喹、利巴韦林等广谱药物的研究，逐渐发展为针对“衣壳蛋白”等特定靶点及“黄酮类化合物”等新型抑制剂的高通量筛选与优化。其二，研究范式由单一病原体研究向更广泛的病毒学背景延伸。例如，与辛德毕斯病毒等的交叉研究，有助于揭示共同作用机制并探索广谱抗病毒策略。近年来，“基因序列”“结构解析”等关键词的持续突现表明该领域研究前沿已迈入以结构生物学与反向遗传学驱动的阶段。通过解析病毒蛋白三维结构，研究前沿正由传统表型筛选向基于精确靶点结构的药物设计推进，这一方法学转变有望突破当前缺乏特效药物的困境。 3.2.2  抗病毒药物药理作用与研究策略  抗病毒药物分析显示，现有研究以化学药为主，中药涉及较少。化学药包括小分子抑制剂、核苷/核苷酸类似物等4类，其中小分子抑制剂最为常见，氯喹和利巴韦林是出现频次较高的代表药物。氯喹作为经典抗疟药，具备广谱体外抗病毒活性，在抑制基孔肯雅病毒侵入[21]和复制[22]方面具有一定效果，展现出良好应用潜力。利巴韦林作为病毒基因组复制抑制剂，可在RNA病毒复制的多个阶段发挥广谱抗病毒作用[23]，与干扰素联合时对基孔肯雅病毒发挥协同抑制效果[24]。目前获批的基孔肯雅病毒特异性药物和疫苗仍然缺乏[25]，因此临床药物的重新定位或再利用成为重要研发策略[26]。该策略不仅可缩短研发周期、降低成本，还因相关药物已具备明确的安全性和药代学特征，具有较高的可行性与转化价值。此外，协同用药或多靶点设计有望降低病毒突变与耐药风险，但大多数抗病毒化合物仍处于早期开发阶段，仍需进一步探索潜在的治疗组合[27]。 3.2.3  天然产物及活性成分  天然产物分析表明，黄酮类和二萜类化合物是主要活性成分。有综述研究指出，黄芩素、芹菜素、黄连素等天然化合物可通过阻断病毒复制发挥抗基孔肯雅病毒活性[28]，其中黄酮类化合物[29]为研究热点可影响病毒RNA合成及蛋白表达；水飞蓟素[30]、黄芩素[31]等黄酮类化合物已被证实具有体外抗基孔肯雅病毒活性，其作用机制可能涉及抑制病毒蛋白结合及干扰复制周期。在二萜类化合物中，双酯型二萜可靶向病毒结构或非结构蛋白，显示出特异性抗病毒潜力[32]。生物药方面虽有单克隆抗体和疫苗研究，但针对基孔肯雅病毒的特效药物开发仍不充分[25]。中药研究则极为有限，仅有穿心莲（1次）和绿茶（2次）被报道。穿心莲内酯可在病毒入侵后阶段阻断基因组复制[33]；绿茶主要成分表没食子儿茶素没食子酸酯在体外显示出抗基孔肯雅病毒活性[34]。尽管当前天然产物的研究尚处于起步阶段，但其独特的优势仍显示出较高的研究潜力：天然产物结构多样、作用机制多元，为新型先导化合物的发现提供了丰富来源[28]；其多靶点、低毒性的特点在应对基孔肯雅病毒方面具有优势，可为协同用药策略的开发提供可能[35]。此外，中医药在缓解发热、关节痛等临床症状方面具有传统经验，挖掘中药的活性成分有助于辅助治疗并改善生活质量[36]。因此，系统开展天然产物筛选与机制研究，可为抗基孔肯雅病毒药物研发提供新思路。 3.3  研究局限性 本研究亦存在一定局限性。首先，数据来源仅限于Web of Science核心合集，未能纳入中文数据库，主要原因在于现有中文文献中关于基孔肯雅热抗病毒治疗的研究数量有限且多为病例报道或综述，难以支撑系统性的文献计量分析，若纳入其中反而可能导致结果偏倚。其次，数据库收录范围及检索式构建方式可能影响结果完整性，导致部分研究未被涵盖。此外，本研究主要基于发文量、关键词及药物频次等宏观指标进行可视化分析，尚不足以全面反映实验质量、研究深度及临床转化进展。未来研究可通过扩展数据库来源并结合更多分析方法对研究内容进行更细致的定性分析，从而更加全面地揭示该领域的发展态势。 4  结论与展望 近20年来，基孔肯雅热抗病毒治疗研究取得了一定进展，但仍面临诸多挑战：①针对基孔肯雅病毒的特异性药物和疫苗仍然缺乏，临床可用药物有限；②多数化学药物仍处于早期开发阶段，天然产物及中药活性成分研究起步较晚，转化应用不足；③研究主要集中于体外和动物模型，临床转化研究有限，缺乏系统的协同用药策略。基于本研究的文献计量学分析及研究趋势，未来研究可重点关注以下方面：①借助结构生物学、分子对接、反向遗传学等技术，开展针对病毒衣壳蛋白及关键非结构蛋白的小分子或天然产物抑制剂研究，提升药物特异性和研发效率；②充分探索天然产物及中草药活性成分，系统筛选并解析黄酮类、二萜类等天然化合物的抗病毒机制，为新型先导化合物的开发及协同用药方案提供理论依据，同时挖掘中药在缓解症状和改善生活质量方面的作用；③加强跨学科方法应用、国际合作与科研资金投入，构建稳固的研究网络，以应对疫情驱动的研究波动，实现长期可持续发展。 利益冲突  所有作者均声明不存在利益冲突 参考文献（略） 来  源：田加盛，杨秋雨，张扬筱妮，廖  丹，严  倩，詹少锋，李  耿，郑文江．基孔肯雅热抗病毒治疗的文献计量研究：现状、趋势与启示  [J]. 中草药, 2026, 57(8): 2943-2953.