Drug repurposing for antimicrobial discovery

Farha, Maya A.; Brown, Eric D.

doi:10.1038/s41564-019-0357-1

Cited by 260 publications

(215 citation statements)

References 178 publications

Supporting

Mentioning

193

Contrasting

Unclassified

Order By: Relevance

“…Rapid virus evolution and the threat of antiviral resistance has motivated research investment in various drug-discovery strategies 5 . One strategy for more timely introducing novel antiviral drugs is 'drug repurposing'.…”

Section: Introductionmentioning

confidence: 99%

In silico synergistic drug repurposing for combating novel coronavirus (COVID-19) outbreaks

Kim

2020

Preprint

View full text Add to dashboard Cite

As the number of novel coronavirus (COVID-19) cases continues to rise, there is a global need for rapid drug development. In this study, we propose a systems pharmacology approach to reposition FDA-approved drug candidates for coronavirus, identify targets and suggest a synergistic drug combination using network pharmacology. We collected 67 genes associated with coronavirus, performed an enrichment analysis to obtain coronavirus-associated disease- pathway and constructed protein-protein interaction (PPI) network based on 67 genes. Total 37 significant disease-pathways were retrieved, and associated FDA-approved drugs were listed for drug repurposing candidates. Our PPI network showed 51 targets from 67 genes and identified IL6 and TNF as potential targets for coronavirus. From the FDA drug list, we selected four drugs that are experimentally used or studied for coronavirus to construct two- drug combinations. From six drug-drug networks, we identified hydroxychloroquine + ribavirin combination had the highest number of overlapping targets (IL6, IL2, IL10, CASP3, IFNA1) from PPI network target list, suggesting a potent synergistic drug combination for coronavirus. With the aim to support the rapid drug development, we suggest a new approach using systems-level drug repurposing for COVID-19 treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

In silico synergistic drug repurposing for combating novel coronavirus (COVID-19) outbreaks

Kim

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…11 Historically, repurposing drugs have emerged as an innovation stream of pharmaceutical development that offers known safety and development pathways for drug developers and has resulted in great success in various disease areas. 12,13 Recently, research efforts have focused on the development of novel antibacterial agents that is distinct from currently used antibiotics, with the objectives of avoiding cross-resistance and reducing the emergence of resistance. 14 Substituted benzene guanidine compounds belonging to amino-guanidine compound class have been used in the treatment of a broad range of diseases and emerged as candidates for further structural modification for new promising drugs.…”

Section: Introductionmentioning

confidence: 99%

<p>In vitro Antibacterial Activity of Isopropoxy Benzene Guanidine Against Multidrug-Resistant <em>Enterococci</em></p>

Zhang¹,

Han²,

Pei³

et al. 2019

IDR

View full text Add to dashboard Cite

“…In the face of drastically rising drug discovery costs, strategies focusing on reducing development timelines such as drug repositioning are also relevant. It is indeed known that small molecule drugs can bind to about 3 to 6 targets on average, opening new avenues to rapidly identify potential novel treatments 58,59 . Molecular modelling techniques and virtual screening can de nitively assist drug repositioning endeavours.…”

Section: Discussionmentioning

confidence: 99%

Targeting furin activity through in silico and in vitro drug repurposing strategy for SARS-CoV-2 spike glycoprotein cleavage repression

Villoutreix

Creemers

Leger³

et al. 2020

Preprint

View full text Add to dashboard Cite

In December 2019, a new coronavirus was identified in the Hubei province of central china and named SRAS-CoV-2. This new virus induces COVID-19, a severe respiratory disease with high death rate. The spike protein (S) of SARS-CoV-2 contains furin-like cleavage sites absent the other SARS-like viruses. The viral infection requires the priming or cleavage of the S protein and such processing seems essential for virus entry into the host cells. Furin is highly expressed in the lung tissue and the expression is further increased in lung cancer, suggesting the exploitation of this mechanism by the virus to mediate enhanced virulence as shown by the higher risk of COVID-19 in these patients. In this study, we used structure- based virtual screening and a collection of about 8,000 unique approved and investigational drugs suitable for docking to search for molecules that could inhibits furin activity. Sulconazole, a broad-spectrum anti-fungal agent, was found to be of potential interest. Using Western blot analysis, Sulconazole was found to inhibit the cleavage of the cell surface furin substrate MT1-MMP that contains two furin cleavage sites similar to those of the SARS- CoV-2 spike protein. Sulconazole and analogs could be interesting for repurposing studies and to probe the yet not fully understood molecular mechanisms involved in cell entry.

show abstract

Drug repurposing for antimicrobial discovery

Cited by 260 publications

References 178 publications

In silico synergistic drug repurposing for combating novel coronavirus (COVID-19) outbreaks

In silico synergistic drug repurposing for combating novel coronavirus (COVID-19) outbreaks

<p>In vitro Antibacterial Activity of Isopropoxy Benzene Guanidine Against Multidrug-Resistant <em>Enterococci</em></p>

Targeting furin activity through in silico and in vitro drug repurposing strategy for SARS-CoV-2 spike glycoprotein cleavage repression

Contact Info

Product

Resources

About