Molnupiravir

RAHWAY, N.J. & MIAMI--( BUSINESS WIRE )--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the initiation of the Phase 3 MOVe-NOW clinical trial to evaluate LAGEVRIO TM (molnupiravir), an investigational oral antiviral COVID-19 medicine, for the treatment of adults with COVID-19 at high risk for disease progression. This double-blind, placebo-controlled, global study is enrolling individuals who are at least 18 years of age, tested positive for SARS-CoV-2 infection, have had COVID-19 symptoms for four days or less, and are not hospitalized. Additionally, the study will only enroll adults who cannot receive nirmatrelvir/ritonavir (NMV/r) due to drug-drug interactions, allergy, previous adverse effects, or inaccessibility. The MOVe-NOW study will use a different formulation of LAGEVRIO that includes two smaller 400-mg tablets per dose (four daily tablets) instead of the currently available four 200-mg capsules per dose (eight daily capsules). The smaller tablets are not currently approved for use in any country. For more information on the trial, visit clinicaltrials.gov . “ COVID-19 remains a leading cause of hospitalization and death around the world, and further studying LAGEVRIO may provide important insights into how it may be used to help prevent severe outcomes in the current COVID-19 environment,” said Dr. Paula Annunziato, senior vice president, infectious diseases and vaccines, Global Clinical Development, Merck Research Laboratories. “ We continue to believe LAGEVRIO may be an important option for people with risk factors like older age, multiple comorbidities, and immunocompromising conditions, who are more likely to advance to severe COVID-19, and for whom other antiviral treatments may not be appropriate because of the potential for drug-drug interactions.” LAGEVRIO is approved or authorized for use in several countries, including Japan, Australia, and available for use in the United States under emergency use authorization, for the treatment of certain adults who have been diagnosed with COVID-19. To date, LAGEVRIO has been used by more than 8.3 million patients worldwide. About the MOVe-NOW Study MOVe-NOW (MK-4482-023, NCT06667700 ) is a Phase 3 multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of orally administered LAGEVRIO compared with placebo in non-hospitalized adults with COVID-19 at high risk for disease progression. The trial is anticipated to enroll approximately 3,082 participants who will be randomized to receive either LAGEVRIO (800 mg) or placebo orally every 12 hours for five days. The study will enroll participants who are at least 18 years of age and have received a positive test for SARS-CoV-2 infection with signs or symptoms attributable to COVID-19 for four days or less and will only enroll adults who cannot receive nirmatrelvir/ritonavir (NMV/r) due to drug-drug interactions, allergy, previous adverse effects, or inaccessibility. The trial is being conducted in 25 markets around the world, including the United States, Japan, Korea, Taiwan, the United Kingdom, France, Italy, Spain, Ukraine, Poland, Mexico, and Colombia, among others. Investigators may decide to treat some study participants with concomitant remdesivir, if available and clinically appropriate per local clinical practice, as local standard of care in addition to LAGEVRIO or placebo. Study investigators should aim to ensure that those who are most vulnerable to severe COVID-19 receive timely access to remdesivir as standard of care. The primary efficacy and safety endpoints of the trial include the percentage of participants who were hospitalized or died for any reason or had a COVID-19-related medically-attended visit through Day 29; the percentage of participants with an adverse event; and the percentage of participants who discontinued LAGEVRIO due to an adverse event. A key secondary endpoint is sustained alleviation without relapse of selected participant-reported COVID-19 signs and symptoms through Day 29. Additional secondary endpoints through Day 29 include evaluation of SARS-CoV-2 viral load, time to sustained resolution without relapse of COVID-19 signs and symptoms, and percentage of participants with clinically important medical interventions associated with a COVID-19-related medically attended visit or hospitalization, or who experienced hospitalization or death due to any cause. The study includes an extended follow up of approximately five and a half months after treatment ends to evaluate endpoints associated with post-acute sequelae of COVID-19 (PASC, or long COVID). Development of PASC will be assessed on Day 29 and during the extended follow-up period (i.e., Day 56, Day 112, and Day 168) based on self-reported COVID-19 signs/symptoms. Authorized Use of LAGEVRIO TM (molnupiravir) in the U.S. LAGEVRIO (molnupiravir) is authorized for use under an Emergency Use Authorization (EUA) for the treatment of adults with mild-to-moderate coronavirus disease 2019 (COVID-19): who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate. LAGEVRIO is not approved for any use, including the treatment of COVID-19, but is authorized for emergency use by the FDA under an Emergency Use Authorization (EUA). The emergency use of LAGEVRIO is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID-19 pandemic under Section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1) unless the declaration is terminated or authorization revoked sooner. Limitations of Authorized Use LAGEVRIO is not authorized: for use in patients who are less than 18 years of age for initiation of treatment in patients hospitalized due to COVID-19. Benefit of treatment with LAGEVRIO has not been observed in subjects when treatment was initiated after hospitalization due to COVID-19 for use for longer than 5 consecutive days for pre-exposure or post-exposure prophylaxis for prevention of COVID-19 LAGEVRIO may only be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs in the therapeutic class to which LAGEVRIO belongs (ie, anti-infectives). Selected Safety Information for LAGEVRIO Contraindications No contraindications have been identified based on the limited available data on the emergency use of LAGEVRIO authorized under this EUA. Warnings and Precautions There are limited clinical data available for LAGEVRIO. Serious and unexpected adverse events may occur that have not been previously reported with LAGEVRIO use. LAGEVRIO is not recommended for use during pregnancy. Based on findings from animal reproduction studies, LAGEVRIO may cause fetal harm when administered to pregnant individuals. There are no available human data on the use of LAGEVRIO in pregnant individuals to evaluate the risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. LAGEVRIO is authorized to be prescribed to a pregnant individual only after the healthcare provider has determined that the benefits would outweigh the risks for that individual patient. If the decision is made to use LAGEVRIO during pregnancy, the prescribing healthcare provider must document that the known and potential benefits and the potential risks of using LAGEVRIO during pregnancy were communicated to the pregnant individual. There is a pregnancy registry that monitors pregnancy outcomes in individuals exposed to LAGEVRIO during pregnancy. The prescribing healthcare provider must document that a pregnant individual was made aware of the pregnancy registry at https://covid-pr.pregistry.com or 1-800-616-3791. Pregnant individuals exposed to LAGEVRIO or their healthcare providers can also report the exposure by contacting Merck Sharp & Dohme LLC, Rahway, NJ USA at 1-877-888-4231. Advise individuals of childbearing potential of the potential risk to a fetus and to use an effective method of contraception correctly and consistently during treatment with LAGEVRIO and for 4 days after the final dose. Prior to initiating treatment with LAGEVRIO, assess whether an individual of childbearing potential is pregnant or not, if clinically indicated. Hypersensitivity reactions, including anaphylaxis, have been reported with LAGEVRIO. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue LAGEVRIO and initiate appropriate medications and/or supportive care. LAGEVRIO is not authorized for use in patients less than 18 years of age because it may affect bone and cartilage growth. The safety and efficacy of LAGEVRIO have not been established in pediatric patients. Adverse Reactions The most common adverse reactions occurring in ≥1% of subjects in the LAGEVRIO treatment group in the Phase 3 double-blind MOVe-OUT study were diarrhea (2% versus placebo at 2%), nausea (1% versus placebo at 1%), and dizziness (1% versus placebo at 1%) all of which were Grade 1 (mild) or Grade 2 (moderate). Serious adverse events occurred in 7% of subjects receiving LAGEVRIO and 10% receiving placebo; most serious adverse events were COVID-19 related. Adverse events leading to death occurred in 2 (<1%) of the subjects receiving LAGEVRIO and 12 (2%) of subjects receiving placebo. Drug Interactions No drug interactions have been identified based on the limited available data on the emergency use of LAGEVRIO. No clinical drug-drug interaction trials of LAGEVRIO with concomitant medications, including other treatments for mild-to-moderate COVID-19, have been conducted. Pregnancy/Breastfeeding There are no data on the presence of molnupiravir or its metabolites in human milk. It is unknown whether molnupiravir has an effect on the breastfed infant or effects on milk production. Based on the potential for adverse reactions in the infant from LAGEVRIO, breastfeeding is not recommended during treatment with LAGEVRIO and for 4 days after the final dose. A lactating individual may consider interrupting breastfeeding and may consider pumping and discarding breast milk during treatment and for 4 days after the last dose of LAGEVRIO. Males of Reproductive Potential While the risk is regarded as low, there is a theoretical risk for LAGEVRIO to affect offspring of treated males based on its mechanism of action. Advise sexually active individuals with partners of childbearing potential to use a reliable method of contraception correctly and consistently during treatment and for at least 3 months after the last dose of LAGEVRIO. The risk beyond three months after the last dose of LAGEVRIO is unknown. Required Reporting for Serious Adverse Events and Medication Errors The prescribing healthcare provider and/or the provider’s designee is/are responsible for mandatory reporting of all serious adverse events and medication errors potentially related to LAGEVRIO within 7 calendar days from the healthcare provider’s awareness of the event. Submit adverse event and medication error reports, using FDA Form 3500, to FDA MedWatch using one of the following methods: Complete and submit the report online: www.fda.gov/medwatch/report.htm Complete and submit a postage-paid FDA Form 3500 ( https://www.fda.gov/media/76299/download ) and return by: Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or Fax to 1-800-FDA-0178 or Call 1-800-FDA-1088 to request a reporting form In addition, please provide a copy of all FDA MedWatch forms to: Merck Sharp & Dohme LLC, Rahway, NJ USA by: Fax: 215-616-5677 E-mail: dpoc.usa@merck.com About LAGEVRIO (molnupiravir) LAGEVRIO (molnupiravir) (MK-4482) is an investigational, orally administered nucleoside analog that inhibits the replication of SARS-CoV-2, the causative agent of COVID‑19. Merck and Ridgeback’s “orange COVID-19 pill” is a Swedish Orange opaque capsule with the Merck corporate logo and “82” printed in white ink, available in certain markets as LAGEVRIO. Molnupiravir was invented at Emory University. Drug Innovation Ventures at Emory (DRIVE), LLC, which was formed by Emory to develop early-stage drug candidates for viral diseases of global concern, advanced molnupiravir through IND submission. Emory/DRIVE received some research funding from the U.S. Department of Defense and the U.S. National Institutes of Health. LAGEVRIO is being developed by Merck in collaboration with Ridgeback Biotherapeutics. Ridgeback received an upfront payment from Merck and also is eligible to receive contingent payments dependent upon the achievement of certain developmental and regulatory approval milestones. Profits from the collaboration are split between the partners equally. Since licensed by Ridgeback, all funds used for the development of LAGEVRIO have been provided by Merck and Ridgeback. About Ridgeback Biotherapeutics Headquartered in Miami, Florida, Ridgeback Biotherapeutics LP is a biotechnology company focused on emerging infectious diseases. Ridgeback developed Ebanga TM for the treatment of Ebola and has a late-stage development pipeline which includes molnupiravir for the treatment of COVID-19. The team at Ridgeback is dedicated to developing life-saving and life-changing solutions for patients and diseases that need champions as well as providing global access to these medicines. In line with Ridgeback’s mission for equitable global access, all Ridgeback services and treatment for Ebola patients in Africa are delivered free of charge. For more information, visit www.ridgebackbio.com . About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., US This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2023, and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( www.sec.gov ). Before prescribing LAGEVRIO™ (molnupiravir), please read the Fact Sheet for Healthcare Providers, including Mandatory Requirements for Administration of LAGEVRIO under Emergency Use Authorization, at https://www.merck.com/eua/molnupiravir-hcp-fact-sheet.pdf and Fact Sheet for Patients and Caregivers at https://www.merck.com/eua/molnupiravir-patient-fact-sheet-english.pdf

“ 点击蓝字 关注我们 《药学进展》抗感染药物主题文章推荐（更新到2024-11-30） PPS  亲爱的读者朋友：     《药学进展》一直致力于为读者提供医药科技前沿与新药研发动态的信息资讯。为了进一步提升阅读体验，我们精心梳理了近年来的文章，按主题细分并实时更新，希望为医药领域专业人士带来更加精准、高效的信息服务，让阅读成为一次真正的知识之旅。本篇重点介绍“抗感染药物主题”（更新到2024-11-30），欢迎关注，一同探索新药研发的无限可能！ 1 抗病毒新靶点药物研发进展及克服耐药性策略 作者：戴文豪，柳红 关键词：抗病毒药物 摘要：病毒感染性疾病是当今及未来人类健康面临的严重威胁。部分病毒感染疾病传播速度快、感染性强、致死率高且具有不可预见性，给全球公共卫生安全体系带来了严峻挑战。自 2007 年世界卫生组织颁布《国际卫生条例》以来，已宣布的 8 次“国际公共卫生紧急事件”均由病毒引起。2024 年 8 月，世界卫生组织再次将猴痘疫情列为“国际公共卫生紧急事件”。流感病毒、乙型肝炎病毒、丙型肝炎病毒、人类免疫缺陷病毒及冠状病毒等，对人类生活产生了深远影响。疫情的频繁发生严重干扰了国际交流、国家稳定、经济发展和人们的生命安全。主要探讨了新冠病毒主蛋白酶的耐药机制和应对策略，以及对其他新靶点新机制抗病毒药物的研究。 本文引用格式： 戴文豪, 柳红. 抗病毒新靶点药物研发进展及克服耐药性策略[J]. 药学进展, 2024, 48(9): 641-643. 微信浏览全文请点这里 抗病毒新靶点药物研发进展及克服耐药性策略 下载PDF请复制以下网址，在PC端浏览器中打开 https://pps.cpu.edu.cn/article/exportPdf?id=a4ecc952-5d49-441e-b747-dd1d7a00b1e6 2 SARS-CoV-2主蛋白酶耐药机制与抗耐药性药物化学策略     作者：谷漫玉，叶冰，高升华，展鹏，刘新泳 摘要：严重急性呼吸综合征冠状病毒 2（severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）主蛋白酶（main protease, Mpro）在病毒复制周期中发挥关键作用，是抗新冠病毒药物的重要靶点。然而，病毒的快速变异引起了对 Mpro 抑制剂的耐药性问题，对全球公共卫生构成严重威胁。对 SARS-CoV-2 Mpro 的耐药机制进行总结，并探讨了新型抗耐药性抑制剂的设计策略。针对Mpro 耐药突变对现有抑制剂疗效的影响，提出了多种基于靶标结构的抗耐药性药物设计方法，如多位点占据、变构位点开发、共价结合等策略，此外还探讨了蛋白降解靶向嵌合体（proteolytic targeting chimera，PROTAC）在降解病毒靶蛋白中的应用。为解决 SARS CoV-2 Mpro 耐药性问题提供了新思路，并为未来可能出现的冠状病毒疫情提供药物筛选和开发的参考。 关键词：严重急性呼吸综合征冠状病毒；主蛋白酶, 耐药机制；抗耐药性药物设计；蛋白降解靶向嵌合体 本文引用格式： 谷漫玉, 叶冰, 高升华, 等. SARS-CoV-2主蛋白酶耐药机制与抗耐药性药物化学策略[J]. 药学进展, 2024, 48(9): 644-660.  微信浏览全文请点这里 独家原创 | 刘新泳、展鹏教授：SARS-CoV-2 主蛋白酶耐药机制与 抗耐药性药物化学策略 下载PDF请复制以下网址，在PC端浏览器中打开 https://pps.cpu.edu.cn/article/exportPdf?id=98d78e29-5257-4b4c-b4ea-f7d419103b27 3 以G-四链体为靶标的小分子抗病毒药物的研究进展 作者：何兴瑞，刘梦婷，王子桉，贾译程，叶向阳，谢恬 摘要：G-四链体（G-quadruplexes，G4s）是由富含串联重复鸟嘌呤（Guanine，G）的DNA或RNA折叠形成的核酸二级结构，广泛存在于所有生物的基因组中，参与调控基因的复制、转录和翻译等多种过程。G4s因其关键的生物学作用而引起人们的兴趣，前期人们主要关注于G4s在癌症中的研究并将其作为抗肿瘤药物的靶点。最近，对病毒基因组学的研究发现许多G4s出现在病毒基因组的调节区，对调节病毒生命周期发挥关键作用。随着新病毒的出现和现有病毒的快速突变，需要开发新的抗病毒靶标和药物。目前现有的大多数抗病毒药物是以病毒的蛋白质为靶标，直接靶向病毒核酸的研究较少。以G4s为靶标的小分子配体的开发有助于帮助理解G4s介导的机制在病毒生命周期中的重要作用，也是一种新的抗病毒药物开发策略。通过对以G4s为靶标的小分子配体在抗病毒中的应用进行总结，旨在为基于G4s的抗病毒药物研发提供参考。 关键词： G-四链体；抗病毒；靶标；小分子配体 本文引用格式： 何兴瑞, 刘梦婷, 王子桉, 等. 以G-四链体为靶标的小分子抗病毒药物的研究进展[J]. 药学进展, 2024, 48(9): 661-674.     微信浏览全文请点这里 独家原创 | 谢恬教授、叶向阳研究员：以 G-四链体为靶标的小分子抗病毒药物的研究进展 下载PDF请复制以下网址，在PC端浏览器中打开 https://pps.cpu.edu.cn/article/exportPdf?id=a4ecc952-5d49-441e-b747-dd1d7a00b1e6 4 乙型肝炎病毒衣壳蛋白装配调节剂的研究及对药物设计的启发     作者：杨泽春，梁明辉，王美，贾海永 摘要：乙型肝炎病毒（hepatitis B virus,HBV）感染是严重威胁人类健康的全球性健康问题，它与肝硬化和肝细胞癌的发展有关，并能引发不同类型的肝损伤。令人遗憾的是，目前尚未实现慢性乙型肝炎（chronic hepatitis B,CHB）的功能性治愈。在深入研究HBV不同蛋白与其配体间的相互作用后发现：特定配体与关键氨基酸的相互作用，实则扮演着化合物抗HBV效力的“开关”。基于这一发现，运用分子对接技术，对蛋白与配体之间的结合模式进行分析。通过对比分析不同配体小分子间的相似之处，成功锁定了具有潜力的药效团，并进一步探讨了氨基酸与这些化合物间可能存在的相互作用。这些研究不仅深化了对HBV衣壳蛋白装配调节剂（capsid assembly modulator,CAM）结构多样性的理解，更在药效团类似性方面取得了新的认识，为抗病毒药物的合理设计提供思路。 关键词：乙型肝炎病毒；衣壳蛋白装配调节剂；分子对接；药效团；药物设计 本文引用格式： 杨泽春, 梁明辉, 王美, 等. 乙型肝炎病毒衣壳蛋白装配调节剂的研究及对药物设计的启发[J]. 药学进展, 2024, 48(9): 675-689.     微信浏览全文请点这里 独家原创 | 贾海永副教授：乙型肝炎病毒衣壳蛋白装配调节剂的研究及对药物设计的启发 下载PDF请复制以下网址，在PC端浏览器中打开 https://pps.cpu.edu.cn/article/exportPdf?id=0e56ae2e-eb03-4d52-af2b-6d7dcefe0f54 5 以金属离子依赖性蛋白为靶标的抗病毒药物研究进展（2021—2023）     作者：李宝虎，徐慧，唐凯，杨锦飞，展鹏 摘要：金属离子依赖性蛋白在病毒复制、组装和宿主细胞侵袭等关键环节中发挥着核心作用，使其成为抗病毒治疗策略的理想靶点。从药物化学的角度出发，综述了2021—2023年，以金属离子依赖性蛋白为靶标的抗病毒药物研究的新进展。详细分析了人类免疫缺陷病毒、人类巨细胞病毒、乙型肝炎病毒、流感病毒、裂谷热病毒、严重急性呼吸综合征冠状病毒等重要病毒的金属离子依赖性蛋白抑制剂，探讨了这些抑制剂的药理活性、作用机制及临床应用潜力。同时强调了设计病毒金属酶抑制剂面临的挑战，如确保高度选择性和特异性、药物稳定性、生物利用度等，以及应对病毒高变异率导致的耐药性问题。最后总结了抗病毒药物研发的新趋势，包括结构基础药物设计、高通量筛选、片段生长和多位点结合策略等，为开发新型高效低毒抗病毒药物提供了新的思路和方法。 关键词：金属离子依赖性蛋白；抗病毒药物；药物设计；抑制剂     本文引用格式： 李宝虎, 徐慧, 唐凯, 等. 以金属离子依赖性蛋白为靶标的抗病毒药物研究进展（2021—2023）[J]. 药学进展, 2024, 48(9): 690-706.     微信浏览全文请点这里 独家原创 | 展鹏教授、杨锦飞教授：以金属离子依赖性蛋白为靶标的抗病毒药物研究进展 （2021—2023） 下载PDF请复制以下网址，在PC端浏览器中打开 https://pps.cpu.edu.cn/article/exportPdf?id=3bb34b1f-c8c7-4610-b7ea-112ea48c53fe 6 抗病毒药物化学研究新进展    作者：展鹏，陈芬儿 关键词：抗病毒药物 摘要：病毒感染性疾病严重威胁着人类的生命健康与安全。20 世纪以来，病毒感染性疾病的不断暴发已经夺走了数千万人的生命。例如，1918年出现的西班牙大流感造成了当时世界约1/3的人口被感染，约 5000 万人死亡；艾滋病自1981年被发现以来，已有约4010 万人死于与艾滋病相关的疾病；2019年底出现的新型冠状病毒感染（COVID-19）被认为是近10年来最致命的病毒大流行之一；2022年5月以来，一些国家和地区先后发现了大量猴痘病毒病例，且已经出现人际传播。2024年5月，全球多地出现登革热疫情。南美洲近期正处在疫情上升阶段，已有21个国家和地区出现登革热疫情，病例数超过520万。对病毒感染性疾病的防治一直是世界公共卫生领域的重大问题。本期专题 4 篇文章分别涉及了 HIV-1 逆转录酶抑制剂、HCV 非结构蛋白 5B（non-structural protein 5B，NS5B）聚合酶抑制剂、流感病毒抑制剂以及SARS-CoV-2 S 蛋白的侵入抑制剂的研究进展。 本文引用格式： 展鹏, 陈芬儿. 抗病毒药物化学研究新进展[J]. 药学进展, 2024, 48(5): 321-324.      微信浏览全文请点这里 独家原创|陈芬儿院士、展鹏教授：抗病毒药物化学研究进展 下载PDF请复制以下网址，在PC端浏览器中打开 https://pps.cpu.edu.cn/article/exportPdf?id=98779c9c-d78c-43c4-aa6e-17fe5e3ab728 7 HIV-1逆转录酶抑制剂的新进展（2021—2023年）     作者：曾依，周家琪，鲍怡翎，刘佳仪，张双双，古双喜 摘要：逆转录酶可将病毒的单链 RNA 逆转录成双链 DNA，在人类免疫缺陷病毒 1 型（HIV-1）的复制周期中发挥着不可替代的作用。逆转录酶抑制剂作为高效抗逆转录病毒疗法的重要组分，在治疗艾滋病方面取得了巨大的成功，大大降低了 HIV-1 患者的发病率和死亡率。然而，随着逆转录酶抑制剂在临床中的长期应用，许多问题逐渐显露，如耐药性和不良反应等。因此，开发出新型高效低毒和抗耐药性的逆转录酶抑制剂具有重要意义。通过对近 3 年靶向 HIV-1 逆转录酶的抗艾滋病药物及相关候选药物的最新研究进展进行综述，以期为新型逆转录酶抑制剂的发现提供参考。     关键词：获得性免疫缺陷综合征; 人类免疫缺陷病毒;逆转录酶抑制剂;  耐药性;药物设计 本文引用格式： 曾依, 周家琪, 鲍怡翎,等. HIV-1逆转录酶抑制剂的新进展（2021—2023年）[J]. 药学进展, 2024, 48(5): 325-334.     微信浏览全文请点这里 独家原创 | 古双喜教授：HIV-1 逆转录酶抑制剂的新进展（2021—2023 年） 下载PDF请复制以下网址，在PC端浏览器中打开 https://pps.cpu.edu.cn/article/exportPdf?id=f4e0ddc5-2378-4abb-9d05-e445987a1e85 8 丙型肝炎病毒非结构蛋白5B聚合酶抑制剂的研究进展     作者：韩迪，薛艺伟，刘风祥，展鹏，徐永涛     摘要：丙型肝炎病毒（hepatitis C virus，HCV）感染是全球范围内的健康挑战。该病毒的非结构蛋白 5B（non-structuralprotein 5B，NS5B）聚合酶对其 RNA 的复制起到了关键作用，是抗 HCV 药物研究的关键靶标。近年来，针对 HCV NS5B 聚合酶抑制剂的研究取得了显著进展。通过对 HCV NS5B 聚合酶的结构特性和功能进行介绍，揭示其在病毒复制过程中的核心作用，同时，以 NS5B 聚合酶为靶标综述了核苷类和非核苷类 2 大类抗 HCV 抑制剂的研究进展。相关研究为抗 HCV 抑制剂的进一步研发提供了重要参考和思路。     关键词：丙型肝炎病毒; 非结构蛋白5B聚合酶; 核苷类抑制剂; 非核苷类抑制剂       本文引用格式： 韩迪, 薛艺伟, 刘风祥, 等. 丙型肝炎病毒非结构蛋白5B聚合酶抑制剂的研究进展[J]. 药学进展, 2024, 48(5): 363-377.     微信浏览全文请点这里 独家原创 | 展鹏教授、徐永涛副教授：丙型肝炎病毒非结构蛋白 5B 聚合酶抑制剂的研究进展 下载PDF请复制以下网址，在PC端浏览器中打开 https://pps.cpu.edu.cn/article/exportPdf?id=0a393f55-21f6-4fc1-8986-20adbc55a327 9 靶向新型冠状病毒S蛋白的侵入抑制剂研究进展     作者：高恒，胡立德，张继伟，贾惠婻，展鹏，刘新泳 摘要：由严重急性呼吸系统综合征冠状病毒 2 型（SARS-CoV-2）引发的新型冠状病毒感染（COVID-19）给人类生命健康和社会经济发展造成了极为严重的影响。随着病毒的持续变异，现有疫苗和治疗药物效果下降，公共卫生风险仍然存在。因此，亟需开发针对新突变株的新靶点和新机制的药物。S蛋白是 SARS-CoV-2 重要的表面蛋白，其介导着病毒侵入宿主细胞这一关键步骤，是抗新型冠状病毒入侵的理想靶点。通过对近年来 S 蛋白抑制剂的研究实例进行分析，对该领域取得的进展进行总结，旨在为抗 SARS-CoV-2药物的研发提供参考。 关键词： 严重急性呼吸系统综合征冠状病毒2型；抗病毒药物；S蛋白；抑制剂；耐药 本文引用格式： 高恒, 胡立德, 张继伟, 等. 靶向新型冠状病毒S蛋白的侵入抑制剂研究进展[J]. 药学进展, 2024, 48(5): 335-349.     微信浏览全文请点这里 独家原创 | 刘新泳教授、展鹏教授：靶向新型冠状病毒 S 蛋白的侵入抑制剂研究进展 下载PDF请复制以下网址，在PC端浏览器中打开 https://pps.cpu.edu.cn/article/exportPdf?id=36692378-5af1-4042-9f3b-61197ff514ec 10 流感病毒抑制剂的研究进展     作者：黎敏科，杨博尧，吴益喜，徐畅，梁欢欢 摘要：流感病毒可引起季节性流感及流感大流行，严重危害人类健康。抗流感病毒药物在控制流感爆发及流行中发挥重要作用。然而，当前可使用的抗流感病毒药物种类过少，且流感病毒极易突变，耐药病毒株不断增长，因此开发可抑制耐药病毒株的新药，以及开发具有全新抗病毒机制的抗流感病毒药物十分必要。通过对靶向流感病毒成分的抗流感病毒药物的研究进展进行综述，重点介绍各靶点药物的种类、作用机制、耐药产生情况以及如何针对耐药靶点进行“老药改造”和新靶点药物的开发，同时也对抗流感病毒药物的未来发展进行讨论，以期为流感病毒感染的治疗及药物研发提供参考。 关键词：流感病毒, 抗病毒药物, 耐药病毒株, 新靶点 本文引用格式： 黎敏科, 杨博尧, 吴益喜,等. 流感病毒抑制剂的研究进展[J]. 药学进展, 2024, 48(5): 350-362.      微信浏览全文请点这里 独家原创 | 梁欢欢教授：流感病毒抑制剂的研究进展 下载PDF请复制以下网址，在PC端浏览器中打开 https://pps.cpu.edu.cn/article/exportPdf?id=22d2d8b0-7da0-4303-8773-0396f6ccb67f 11 提升新药自主研发能力,应对未来传染病大流行     作者：张文宏，王越  摘要：自2022年12月国内各地经历了第一轮新冠感染高峰至今,XBB作为奥密克戎亚型变异毒株成为当前的主流毒株。尽管现阶段主要的流行毒株致病性显著减弱,但其超强传播性带来的疾病负担对老年人、基础病患者等高风险人群仍然是重大威胁。充足的药物储备和供应,对有效降低高风险人群重症率尤为关键。继辉瑞公司的奈玛特韦/利托那韦和默沙东的molnupiravir在国内获批上市后,国内药企亦针对抗新冠病毒小分子药物管线积极加快布局。     关键词：高风险人群;疾病负担;感染高峰;利托那韦;小分子药物;辉瑞公司;自主研发能力;变异毒株;     本文引用格式： 张文宏,王越.提升新药自主研发能力,应对未来传染病大流行[J].药学进展,2023,47(7):481-483.     微信浏览全文请点这里 独家原创 | 张文宏教授、王越博士：提升新药自主研发能力，应对未来传染病大流行 下载PDF请复制以下网址，在PC端浏览器中打开 https://pps.cpu.edu.cn/article/exportPdf?id=7829951f-2985-42ad-87de-8902c4a40304 12 先诺欣®——国产首款靶向3C样蛋白酶的抗新冠病毒创新药     作者：陆磊，吴琪，王峰 摘要：新型冠状病毒流行是近3年来全球范围传播速度最快、感染范围最广、防控难度最大的突发公共卫生事件。国产首款靶向3C样蛋白酶的抗新冠病毒创新药先诺欣®（先诺特韦片/利托那韦片组合包装）的获批上市，为我国新型冠状病毒感染的治疗提供了新的用药选择。简介先诺欣®的研发与新药申请历程及相关经验，旨在为突发公共卫生事件急需药物的研发及注册提供参考。 关键词：新型冠状病毒；3C样蛋白酶；先诺欣®；先诺特韦；利托那韦 本文引用格式： 陆磊, 吴琪, 王峰. 先诺欣®——国产首款靶向3C样蛋白酶的抗新冠病毒创新药[J]. 药学进展, 2023, 47(7): 484-488. 微信浏览全文请点这里 独家原创 | 王峰博士：先诺欣 ®——国产首款靶向 3C 样蛋白酶的抗新冠病毒创新药 下载PDF请复制以下网址，在PC端浏览器中打开 https://pps.cpu.edu.cn/article/exportPdf?id=069aaead-68e4-40b9-8cab-f2b9fa7224da 感谢您阅读《药学进展》微信平台原创好文，也欢迎各位读者转载、引用。 《药学进展》杂志由国家教育部主管、中国药科大学和中国药学会共同主办，中国科技核心期刊（中国科技论文统计源期刊）。刊物以反映药学科研领域的新方法、新成果、新进展、新趋势为宗旨，以综述、评述、行业发展报告为特色，以药学学科进展、技术进展、新药研发各环节技术信息为重点，是一本专注于医药科技前沿与产业动态的专业媒体。 《药学进展》注重内容策划、加强组稿约稿、深度挖掘、分析药学信息资源、在药学学科进展、科研思路方法、靶点机制探讨、新药研发报告、临床用药分析、国际医药前沿等方面初具特色；特别是医药信息内容以科学前沿与国家战略需求相合，更加突出前瞻性、权威性、时效性、新颖性、系统性、实战性。根据最新统计数据，刊物篇均下载率连续三年蝉联我国医药期刊榜首，复合影响因子1.216，具有较高的影响力。 《药学进展》编委会由国家重大专项化学药总师陈凯先院士担任主编，编委由新药研发技术链政府监管部门、高校科研院所、制药企业、临床医院、CRO、金融资本及知识产权相关机构近两百位极具影响力的专家组成。 联系《药学进展》↓↓↓ 编辑部官网：pps.cpu.edu.cn； 邮箱：yxjz@163.com； 电话：025-83271227。 欢迎投稿、订阅！ 往期推荐 聚焦“兴药为民·2023生物医药创新融合发展大会”“兴药为民·2023生物医药创新融合发展大会”盛大启幕！院士专家齐聚杭城，绘就生物医药前沿赛道新蓝图“兴药强刊”青年学者论坛暨《药学进展》第二届青年编委会议成功召开“兴药为民·2023生物医药创新融合发展大会”路演专场圆满收官！校企合作新旅程已启航 我知道你在看哟