Identification of Novel 5,6-Dimethoxyindan-1-one Derivatives as Antiviral Agents

Patil, Siddappa A.; Patil, Vikrant; Patil, Renukadevi; Beaman, Kenneth D.; Patil, Shivaputra A.

doi:10.2174/1573406413666170330094822

Cited by 16 publications

(15 citation statements)

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“…The drug annotations were obtained from PubChem, DrugBank, DrugCentral, PubMed and clinicaltrials.gov databases (Table S1) Ursu et al, 2019;Wishart et al, 2018). The information on virus families were exported from Virus Pathogen Database and Analysis Resource (Table S2) (Pickett et al, 2012 Emerging BSAAs, such as 5,6-dimethoxyindan-1-one, saliphenylhalamide, and GS-5734 (Denisova et al, 2012;Kuivanen et al, 2017;Muller et al, 2011;Muller et al, 2014;Patil et al, 2017;Sheahan et al, 2017), whose safety profiles in humans are not yet available, are not included in the database. However, they could serve as valuable antivirals in the future, pending the results of further pre-clinical and clinical investigations.…”

Section: Bsaa Databasementioning

confidence: 99%

Discovery and development of safe-in-man broad-spectrum antiviral agents

Andersen

Ianevski

Lysvand

et al. 2020

International Journal of Infectious Diseases

198

108

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# Contributed equally J o u r n a l P r e -p r o o f Highlights  We reviewed discovery and development process of broad-spectrum antiviral agents.  We summarized the information on 119 safe-in-man agents in freely accessible database.  Further studies will increase the number of broad-spectrum antivirals, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections. Abstract: Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and reemerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 119 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections. J o u r n a l P r e -p r o o f 2015). Antiviral drugs and vaccines are used to fight viral infections in human (De Clercq and Li, 2016; Marston et al., 2014). Previously, there has been a focus on "one drug, one virus" dogma, which relied on targeting virus-specific factors. A counterpoint to this is "one drug, multiple viruses" paradigm, which came with the discovery of broad-spectrum antiviral agents (BSAAs), small-molecules that inhibit a wide range of human viruses (Bekerman and Einav, 2015; de Clercq and Montgomery, 1983; Debing et al., 2015; Ianevski et al., 2019; Rada and Dragun, 1977; Sidwell et al., 1972). This paradigm was based on the observation that different viruses utilize similar pathways and host factors to replicate inside a cell (Bosl et al., 2019). Although the concept of BSAAs has been around for almost 50 years, the field received a new impetus with recent outbreaks of Ebola, Zika, Dengue, influenza and other viral infections, the discovery of novel host-directed agents as well as development of drug repositioning methodology. Drug repurposing, also called repositioning, redirecting, reprofiling, is a strategy for generating additional value from an existing drug by targeting disease other than that for which it was originally intended (Nishimura and Hara, 2018; Pushpakom et al., 2019). This has significant advantages over new drug discovery since chemical synthesis steps, manufacturing processes, reliable safety, and pharmacokinetic properties in pre-clinical (animal model) and early clinical developmental phases (phase 0, I and IIa) are already available (Figure 1). Therefore, repositioning of launched or even failed drugs to viral diseases provides unique translational opportunities, includi...

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Section: Bsaa Databasementioning

confidence: 99%

Discovery and development of safe-in-man broad-spectrum antiviral agents

Andersen

Ianevski

Lysvand

et al. 2020

International Journal of Infectious Diseases

198

108

View full text Add to dashboard Cite

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“…Emerging BSAAs, such as 5,6-dimethoxyindan-1-one, saliphenylhalamide, and GS-5734 (22,49,(106)(107)(108)(109), whose safety profiles in humans are not yet available, are not included in the database. However, they could serve as valuable antivirals in the future, pending the results of further preclinical and clinical investigations.…”

Section: Bsaa Databasementioning

confidence: 99%

Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents

Andersen¹,

Ianevski²,

Lysvand³

et al. 2019

Preprint

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Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed development process of BSAAs and summarized the information on 119 safe-in-man agents in freely accessible database (https://drugvirus.info/). The number of BSAAs will be increased, their developmental status will be updated, spectrum of their indications will be expanded, as well as BSAA combinations will be approved pending the results of further pre-clinical and clinical studies.

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“…Emerging BSAAs, such as 5,6-dimethoxyindan-1-one, saliphenylhalamide, and GS-5734 (22,42,90,(93)(94)(95), whose safety profiles in humans are not yet available, could serve as valuable antivirals in the future, pending the results of further pre-clinical and clinical investigations. The follow-up studies as well as the results of on-going, finalized or terminated clinical trials should be made publicly available to allow posterization and translation of emerging and existing BSAAs into clinical practice.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents

Andersen¹,

Ianevski²,

Lysvand³

et al. 2019

Preprint

View full text Add to dashboard Cite

Viral diseases are one of the leading causes of morbidity and mortality in the world. Broad-spectrum antiviral agents (BSAAs) are key players in control of human viral diseases. Here, we reviewed the discovery and development process of BSAAs, focusing on compounds with available safety profiles in human. In addition, we summarized the information on approved, investigational and experimental safe-in-man BSAAs in freely accessible database at https://drugvirus.info/. The number of approved BSAAs will be increased as well as their spectrum of indications will be expanded pending the results of further pre-clinical and clinical studies. This will ultimately reinforce the arsenal of available antiviral options and provide better protection of general population from emerging and re-emerging viral diseases.

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Identification of Novel 5,6-Dimethoxyindan-1-one Derivatives as Antiviral Agents

Abstract: Our research identified a novel 5,6-dimethoxyindan-1-one analog (compound 7), as a potent antiviral agent for vaccinia virus, and heterocyclic chalcone analog (compound 9) as a broad spectrum antiviral agent.

Cited by 16 publications

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Discovery and development of safe-in-man broad-spectrum antiviral agents

Discovery and development of safe-in-man broad-spectrum antiviral agents

Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents

Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents

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