Drug Repurposing for Viral Infectious Diseases: How Far Are We?
Drug Repurposing for Viral Infectious Diseases: How Far Are We?
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DOI：
10.1016/j.tim.2018.04.004
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发表时间：
2018-10
影响因子：
15.9
通讯作者：
Loregian A
中科院分区：
文献类型：
--
作者：
Mercorelli B;Palù G;Loregian A
尽管最近在控制一些病毒病原体方面取得了进展，但大多数病毒感染仍然缺乏特异性治疗。事实上，对抗“老”病毒、新出现的病毒和重新出现的病毒的有效治疗策略的需要并不因新抗病毒药物的批准而改变。在过去的几年里，药物再利用与药物验证的创新方法以及适当的动物模型相结合，大大有助于识别新的抗病毒分子和治疗干预的靶点。在这篇综述中，我们描述了药物再利用在抗病毒药物发现的主要策略，讨论了最有前途的候选人，可以被重新利用来治疗病毒感染，并分析了这种流行的药物发现策略可能的警告。重新利用现有药物是一种新兴的战略，可加快批准有效和安全的治疗方法，例如用于治疗孤儿药疾病。抗病毒活性的新适应症可以通过对先前已知的靶标或新的抗病毒靶标起作用来鉴定不同来源的分子，这些分子显示出再利用的潜力。目标验证的创新方法（例如，通过CRISPR/Cas9进行基因编辑）和新的实验模型（例如，类器官）允许鉴定新的抗病毒剂和解开病毒发病机制的分子途径。药物再利用已经成功地确定了有希望的候选药物，这些药物可以开辟新的治疗途径，以对抗当前的病毒病原体和可能出现的病毒。
Despite the recent advances in controlling some viral pathogens, most viral infections still lack specific treatment. Indeed, the need for effective therapeutic strategies to combat ‘old’, emergent, and re-emergent viruses is not paralleled by the approval of new antivirals. In the past years, drug repurposing combined with innovative approaches for drug validation, and with appropriate animal models, significantly contributed to the identification of new antiviral molecules and targets for therapeutic intervention. In this review, we describe the main strategies of drug repurposing in antiviral discovery, discuss the most promising candidates that could be repurposed to treat viral infections, and analyze the possible caveats of this trendy strategy of drug discovery. Repurposing existing drugs is an emerging strategy for expediting the approval of effective and safe therapeutics, such as for the treatment of orphan drug diseases. New indications for antiviral activity can be identified for molecules of different origins showing repurposing potential by acting against a previously known target or a new antiviral target. Innovative approaches for target validation (e.g., gene editing by CRISPR/Cas9) and new experimental models (e.g., organoids) allowed the identification of novel antiviral agents and the unraveling of molecular pathways underlying viral pathogenesis. Drug repurposing has successfully identified promising candidate drugs that can open new therapeutic avenues to counteract current viral pathogens and possible emerging viruses.
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影响因子：
7.6
作者：
Gardner, Thomas J.;Cohen, Tobias;Redmann, Veronika;Lau, Zerlina;Felsenfeld, Dan;Tortorella, Domenico
通讯作者：
Tortorella, Domenico
影响因子：
5.2
作者：
Droebner K;Haasbach E;Dudek SE;Scheuch G;Nocker K;Canisius S;Ehrhardt C;von Degenfeld G;Ludwig S;Planz O
通讯作者：
Planz O
DOI：
10.1073/pnas.0912966107
发表时间：
2010-01-05
影响因子：
11.1
作者：
Gastaminza, Pablo;Whitten-Bauer, Christina;Chisari, Francis V.
通讯作者：
Chisari, Francis V.
影响因子：
30.3
作者：
Barrows NJ;Campos RK;Powell ST;Prasanth KR;Schott-Lerner G;Soto-Acosta R;Galarza-Muñoz G;McGrath EL;Urrabaz-Garza R;Gao J;Wu P;Menon R;Saade G;Fernandez-Salas I;Rossi SL;Vasilakis N;Routh A;Bradrick SS;Garcia-Blanco MA
通讯作者：
Garcia-Blanco MA
影响因子：
2.5
作者：
Arabi YM;Alothman A;Balkhy HH;Al-Dawood A;AlJohani S;Al Harbi S;Kojan S;Al Jeraisy M;Deeb AM;Assiri AM;Al-Hameed F;AlSaedi A;Mandourah Y;Almekhlafi GA;Sherbeeni NM;Elzein FE;Memon J;Taha Y;Almotairi A;Maghrabi KA;Qushmaq I;Al Bshabshe A;Kharaba A;Shalhoub S;Jose J;Fowler RA;Hayden FG;Hussein MA;And the MIRACLE trial group
通讯作者：
And the MIRACLE trial group