Recent advances in small-molecular therapeutics for COVID-19.

IF 5.1 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Lei Zhong, Zhipeng Zhao, Xuerun Peng, Jun Zou, Shengyong Yang
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引用次数: 9

Abstract

The COVID-19 pandemic poses a fundamental challenge to global health. Since the outbreak of SARS-CoV-2, great efforts have been made to identify antiviral strategies and develop therapeutic drugs to combat the disease. There are different strategies for developing small molecular anti-SARS-CoV-2 drugs, including targeting coronavirus structural proteins (e.g. spike protein), non-structural proteins (nsp) (e.g. RdRp, Mpro, PLpro, helicase, nsp14, and nsp16), host proteases (e.g. TMPRSS2, cathepsin, and furin) and the pivotal proteins mediating endocytosis (e.g. PIKfyve), as well as developing endosome acidification agents and immune response modulators. Favipiravir and chloroquine are the anti-SARS-CoV-2 agents that were identified earlier in this epidemic and repurposed for COVID-19 clinical therapy based on these strategies. However, their efficacies are controversial. Currently, three small molecular anti-SARS-CoV-2 agents, remdesivir, molnupiravir, and Paxlovid (PF-07321332 plus ritonavir), have been granted emergency use authorization or approved for COVID-19 therapy in many countries due to their significant curative effects in phase III trials. Meanwhile, a large number of promising anti-SARS-CoV-2 drug candidates have entered clinical evaluation. The development of these drugs brings hope for us to finally conquer COVID-19. In this account, we conducted a comprehensive review of the recent advances in small molecule anti-SARS-CoV-2 agents according to the target classification. Here we present all the approved drugs and most of the important drug candidates for each target, and discuss the challenges and perspectives for the future research and development of anti-SARS-CoV-2 drugs.

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新冠肺炎小分子治疗的最新进展。
2019冠状病毒病大流行对全球卫生构成根本性挑战。自SARS-CoV-2爆发以来,人们在确定抗病毒策略和开发治疗药物方面做出了巨大努力。开发小分子抗sars - cov -2药物有不同的策略,包括针对冠状病毒结构蛋白(如刺突蛋白)、非结构蛋白(如RdRp、Mpro、PLpro、解旋酶、nsp14和nsp16)、宿主蛋白酶(如TMPRSS2、组织蛋白酶和furin)和介导内吞作用的关键蛋白(如PIKfyve),以及开发内核体酸化剂和免疫反应调节剂。法匹拉韦和氯喹是在此次疫情早期发现的抗sars - cov -2药物,并根据这些策略重新用于COVID-19临床治疗。然而,它们的功效是有争议的。目前,三种小分子抗sars - cov -2药物remdesivir、molnupiravir和Paxlovid (PF-07321332 +利托那韦)由于在III期试验中疗效显著,已在许多国家获得紧急使用授权或批准用于COVID-19治疗。与此同时,大量有前景的抗sars - cov -2候选药物已进入临床评估阶段。这些药物的开发为我们最终战胜COVID-19带来了希望。在这篇文章中,我们根据靶标分类对小分子抗sars - cov -2药物的最新进展进行了全面的综述。在这里,我们介绍了所有已批准的药物和针对每个靶点的大多数重要候选药物,并讨论了抗sars - cov -2药物未来研发的挑战和前景。
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来源期刊
Precision Clinical Medicine
Precision Clinical Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
10.80
自引率
0.00%
发文量
26
审稿时长
5 weeks
期刊介绍: Precision Clinical Medicine (PCM) is an international, peer-reviewed, open access journal that provides timely publication of original research articles, case reports, reviews, editorials, and perspectives across the spectrum of precision medicine. The journal's mission is to deliver new theories, methods, and evidence that enhance disease diagnosis, treatment, prevention, and prognosis, thereby establishing a vital communication platform for clinicians and researchers that has the potential to transform medical practice. PCM encompasses all facets of precision medicine, which involves personalized approaches to diagnosis, treatment, and prevention, tailored to individual patients or patient subgroups based on their unique genetic, phenotypic, or psychosocial profiles. The clinical conditions addressed by the journal include a wide range of areas such as cancer, infectious diseases, inherited diseases, complex diseases, and rare diseases.
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