A critical overview of computational approaches employed for COVID-19 drug discovery.
A critical overview of computational approaches employed for COVID-19 drug discovery.
复制标题
新冠肺炎药物发现所采用的计算方法的关键概述。
DOI：
10.1039/d0cs01065k
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发表时间：
2021-08-21
影响因子：
46.2
通讯作者：
Tropsha A
中科院分区：
文献类型：
--
作者：
Muratov EN ;Amaro R ;Andrade CH ;Brown N ;Ekins S ;Fourches D ;Isayev O ;Kozakov D ;Medina-Franco JL ;Merz KM ;Oprea TI ;Poroikov V ;Schneider G ;Todd MH ;Varnek A ;Winkler DA ;Zakharov AV ;Cherkasov A ;Tropsha A
COVID-19在全球范围内导致大量感染和死亡，并给社会和经济带来自大萧条以来最严重的破坏。为了应对这场毁灭性的大流行病，出现了大量的实验和计算研究工作，以了解和描述这种疾病并快速开发诊断方法、疫苗和药物，超过13万篇与COVID-19相关的研究论文发表在同行评审期刊上或存放在预印本服务器上。大部分研究工作都集中在发现新的候选药物或重新利用现有药物对抗COVID-19，许多此类项目都是完全计算或计算机辅助的实验研究。在此，我们提供了一个专家概述的关键计算方法及其应用的发现COVID-19的小分子疗法，已在研究文献中报道。我们进一步概述，在COVID-19大流行的第一年之后，药物再利用似乎并没有产生快速和全球性的解决方案。然而，几种已知的药物已在临床上用于治愈COVID-19患者，一些重新使用的药物继续在临床试验中被考虑，沿着几种新的临床候选药物。我们认为，真正有影响力的计算工具必须提供可操作的、可通过实验验证的假设，从而能够发现新药和药物组合，而开放科学和快速共享研究成果对于加速开发新型、急需的COVID-19疗法至关重要。我们涵盖了不同的方法，计算方法和案例研究，说明了正在进行的努力，以开发可行的候选药物治疗COVID-19。
COVID-19 has resulted in huge numbers of infections and deaths worldwide and brought the most severe disruptions to societies and economies since the Great Depression. Massive experimental and computational research effort to understand and characterize the disease and rapidly develop diagnostics, vaccines, and drugs has emerged in response to this devastating pandemic and more than 130 000 COVID-19-related research papers have been published in peer-reviewed journals or deposited in preprint servers. Much of the research effort has focused on the discovery of novel drug candidates or repurposing of existing drugs against COVID-19, and many such projects have been either exclusively computational or computer-aided experimental studies. Herein, we provide an expert overview of the key computational methods and their applications for the discovery of COVID-19 small-molecule therapeutics that have been reported in the research literature. We further outline that, after the first year the COVID-19 pandemic, it appears that drug repurposing has not produced rapid and global solutions. However, several known drugs have been used in the clinic to cure COVID-19 patients, and a few repurposed drugs continue to be considered in clinical trials, along with several novel clinical candidates. We posit that truly impactful computational tools must deliver actionable, experimentally testable hypotheses enabling the discovery of novel drugs and drug combinations, and that open science and rapid sharing of research results are critical to accelerate the development of novel, much needed therapeutics for COVID-19. We cover diverse methodologies, computational approaches, and case studies illustrating the ongoing efforts to develop viable drug candidates for treatment of COVID-19.
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影响因子：
3.6
作者：
Blaschke T;Olivecrona M;Engkvist O;Bajorath J;Chen H
通讯作者：
Chen H
影响因子：
14.9
作者：
Avram S;Bologa CG;Holmes J;Bocci G;Wilson TB;Nguyen DT;Curpan R;Halip L;Bora A;Yang JJ;Knockel J;Sirimulla S;Ursu O;Oprea TI
通讯作者：
Oprea TI
影响因子：
14.8
作者：
Arrowsmith CH;Audia JE;Austin C;Baell J;Bennett J;Blagg J;Bountra C;Brennan PE;Brown PJ;Bunnage ME;Buser-Doepner C;Campbell RM;Carter AJ;Cohen P;Copeland RA;Cravatt B;Dahlin JL;Dhanak D;Edwards AM;Frederiksen M;Frye SV;Gray N;Grimshaw CE;Hepworth D;Howe T;Huber KV;Jin J;Knapp S;Kotz JD;Kruger RG;Lowe D;Mader MM;Marsden B;Mueller-Fahrnow A;Müller S;O'Hagan RC;Overington JP;Owen DR;Rosenberg SH;Roth B;Ross R;Schapira M;Schreiber SL;Shoichet B;Sundström M;Superti-Furga G;Taunton J;Toledo-Sherman L;Walpole C;Walters MA;Willson TM;Workman P;Young RN;Zuercher WJ
通讯作者：
Zuercher WJ
影响因子：
5.6
作者：
Bizon, Chris;Cox, Steven;Tropsha, Alexander
通讯作者：
Tropsha, Alexander
影响因子：
64.5
作者：
Bouhaddou, Mehdi;Memon, Danish;Krogan, Nevan J.
通讯作者：
Krogan, Nevan J.