ArticleBriefings in bioinformatics2022
Systematic optimization of host-directed therapeutic targets and preclinical validation of repositioned antiviral drugs.
Article in Briefings in bioinformatics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed, 6 citations in OpenAlex.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of host protein functions using established drugs produces a promising antiviral effect with excellent safety profiles, decreased incidence of resistant variants and favorable balance of costs and risks. Genomic methods have produced a large number of robust host factors, providing candidates for identification of antiviral drug targets. However, there is a lack of global perspectives and systematic prioritization of known virus-targeted host proteins (VTHPs) and drug targets. There is also a need for host-directed repositioned antivirals. Here, we integrated 6140 VTHPs and grouped viral infection modes from a new perspective of enriched pathways of VTHPs. Clarifying the superiority of nonessential membrane and hub VTHPs as potential ideal targets for repositioned antivirals, we proposed 543 candidate VTHPs. We then presented a large-scale drug-virus network (DVN) based on matching these VTHPs and drug targets. We predicted possible indications for 703 approved drugs against 35 viruses and explored their potential as broad-spectrum antivirals. In vitro and in vivo tests validated the efficacy of bosutinib, maraviroc and dextromethorphan against human herpesvirus 1 (HHV-1), hepatitis B virus (HBV) and influenza A virus (IAV). Their drug synergy with clinically used antivirals was evaluated and confirmed. The results proved that low-dose dextromethorphan is better than high-dose in both single and combined treatments. This study provides a comprehensive landscape and optimization strategy for druggable VTHPs, constructing an innovative and potent pipeline to discover novel antiviral host proteins and repositioned drugs, which may facilitate their delivery to clinical application in translational medicine to combat fatal and spreading viral infections.
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