Medicinal chemistry strategies for discovering antivirals effective against drug-resistant viruses

Ma, Yue; Frutos-Beltrán, Estrella; Kang, Dongwei; Pannecouque, Christophe; Clercq, Erik De; Menéndez‐Arias, Luis; Liu, Xinyong; Zhan, Peng

doi:10.1039/d0cs01084g

Cited by 124 publications

(69 citation statements)

References 247 publications

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“…However, just one antiviral drug is usually not enough for a safe cure with this type of infectious agent, due to the facile emergence of mutations, which may lead to strains resistant to the drug, as already well documented for other widespread viral infections, such as HIV, HCV, Ebola, etc. [16][17][18][19][20][21] and mentioned above to be the case of SARS-CoV-2 too. Thus, the development of novel specific and effective antiviral agents that target various coronavirus (or even host) proteins should continue in order to supplement the vaccine and MAb therapeutics with such small-molecule drugs.…”

Section: Coronavirusesmentioning

confidence: 84%

Coronaviruses

Supuran

2021

Expert Opinion on Therapeutic Patents

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Section: Coronavirusesmentioning

confidence: 84%

Coronaviruses

Supuran

2021

Expert Opinion on Therapeutic Patents

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“…For such reasons, the multiple targeting approach was initially considered mainly for multifactorial diseases such as cancer 6–8 , Alzheimer’s and other neurodegenerative diseases 9 , 10 , schizophrenia 11 , etc. However, more recently the approach was successfully extended to the discovery of antibiotics 12 and antiviral drugs 13 , proving that it may be a general one.…”

Section: Introductionmentioning

confidence: 99%

Multitargeting approaches involving carbonic anhydrase inhibitors: hybrid drugs against a variety of disorders

Supuran

2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Carbonic anhydrases (CAs, EC 4.2.1.1) are enzymes involved in a multitude of diseases, and their inhibitors are in clinical use as drugs for the management of glaucoma, epilepsy, obesity, and tumours. In the last decade, multitargeting approaches have been proposed by hybridisation of CA inhibitors (CAIs) of sulphonamide, coumarin, and sulphocoumarin types with NO donors, CO donors, prostaglandin analogs, β-adrenergic blockers, non-steroidal anti-inflammatory drugs, and a variety of anticancer agents (cytotoxic drugs, kinase/telomerase inhibitors, P-gp and thioredoxin inhibitors). Many of the obtained hybrids showed enhanced efficacy compared to the parent drugs, making multitargeting an effective and innovative approach for various pharmacological applications.

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“…Outbreaks of diseases caused by coronaviruses SARS-CoV (2002–2004), MERS-CoV (2012, 2014, 2015), filovirus Ebola (2014–2015, 2018–2019), as well as the current pandemic caused by coronavirus SARS-CoV-2 (2019–to date), has stimulated extensive research on antiviral compounds [ 1 , 2 , 3 , 4 , 5 , 6 ] and has shown the importance of the availability of approved broad-spectrum antiviral drugs suitable for rapid repurposing or repositioning [ 7 , 8 , 9 , 10 , 11 , 12 ] to combat emerging threats. The need for such drugs was postulated in 2015 [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Photosensitizing Antivirals

et al. 2021

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Antiviral action of various photosensitizers is already summarized in several comprehensive reviews, and various mechanisms have been proposed for it. However, a critical consideration of the matter of the area is complicated, since the exact mechanisms are very difficult to explore and clarify, and most publications are of an empirical and “phenomenological” nature, reporting a dependence of the antiviral action on illumination, or a correlation of activity with the photophysical properties of the substances. Of particular interest is substance-assisted photogeneration of highly reactive singlet oxygen (1O2). The damaging action of 1O2 on the lipids of the viral envelope can probably lead to a loss of the ability of the lipid bilayer of enveloped viruses to fuse with the lipid membrane of the host cell. Thus, lipid bilayer-affine 1O2 photosensitizers have prospects as broad-spectrum antivirals against enveloped viruses. In this short review, we want to point out the main types of antiviral photosensitizers with potential affinity to the lipid bilayer and summarize the data on new compounds over the past three years. Further understanding of the data in the field will spur a targeted search for substances with antiviral activity against enveloped viruses among photosensitizers able to bind to the lipid membranes.

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Medicinal chemistry strategies for discovering antivirals effective against drug-resistant viruses

Abstract: This review summarizes current advances in medicinal chemistry aimed at the discovery of antiviral compounds specifically targeted against drug-resistant strains.

Cited by 124 publications

References 247 publications

Coronaviruses

Coronaviruses

Multitargeting approaches involving carbonic anhydrase inhibitors: hybrid drugs against a variety of disorders

Photosensitizing Antivirals

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