Repurposing of Anticancer Drugs Expands Possibilities for Antiviral and Anti-Inflammatory Discovery in COVID-19

Aldea, Mihaela; Michot, Jean‐Marie; Danlos, François‐Xavier; Ribas, Antoni; Soria, Jean‐Charles

doi:10.1158/2159-8290.cd-21-0144

Cited by 24 publications

(19 citation statements)

References 87 publications

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“…Essential pharmacological treatment options include antiviral agents (to reduce viral load) as well as immunomodulators and biologics [ 2 ], particularly as it is the inflammatory response and release of proinflammatory cytokines (the “cytokine storm” characteristic of ARDS) rather than SARS-CoV-2 infection per se that is fatal [ 5 ]. Of interest, some antiviral agents also act as immunomodulators [ 1 , 6 ].…”

Section: Prevention Better Than Covid-19 Curementioning

confidence: 99%

“…Most treatment aims to prevent or treat severe COVID-19 in high-risk patients. These include people who are older, obese or pregnant, as well as those with cancer (especially leukaemia or lymphoma), diabetes, or respiratory, cardiovascular and other comorbidities [ 6 ].…”

Section: Small Molecules More Accessible If Supply Chain Workmentioning

confidence: 99%

“…Investigations show that cytokines that drive the most severe illness include interleukins (ILs) 2, 6, 7 and 8, tumour necrosis factor (TNF)-⍺ and interferon (INF)-ɣ [ 5 , 6 ]; for some of these cytokines, antagonists already exist [ 5 ]. Granulocyte-colony stimulating factor, INF-γ-inducible protein 10, macrophage inflammatory protein 1-α (MIP-1α), and monocyte chemoattractant protein-1 (MCP-1) are also of interest [ 5 ].…”

Section: Small Molecules More Accessible If Supply Chain Workmentioning

confidence: 99%

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Emerging small molecule antivirals may fit neatly into COVID-19 treatment

Fenton

Keam

2022

Drugs Ther Perspect

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Numerous treatments exist for COVID-19, the illness caused by SARS-CoV-2 virus, although most are not well established; among these are several small molecule antiviral agents. Intravenous remdesivir is an established treatment worldwide for inpatients and in some countries is also available for use in non-hospitalised high risk patients to prevent progression to severe disease and hospitalization. Oral molnupiravir and oral nirmatrelvir-ritonavir are also available in several countries to prevent progression to severe disease and hospitalization for high-risk outpatients. Many other antiviral small molecules that may have therapeutic potential are under investigation in clinical trials. This article provides a summary of key molecular targets, pharmacology and preliminary data on the efficacy and safety of small molecule antiviral agents being investigated for the treatment of COVID-19.

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Section: Prevention Better Than Covid-19 Curementioning

confidence: 99%

Section: Small Molecules More Accessible If Supply Chain Workmentioning

confidence: 99%

Section: Small Molecules More Accessible If Supply Chain Workmentioning

confidence: 99%

See 1 more Smart Citation

Emerging small molecule antivirals may fit neatly into COVID-19 treatment

Fenton

Keam

2022

Drugs Ther Perspect

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“…Recently, multiple anticancer drugs have been repurposed of their capabilities in antiviral treatments ( Aldea et al, 2021 ; Xu Y. et al, 2021 ). For instance, β-arrestin 2 is a regulator of G protein-coupled receptor (GPCR) signaling pathways, promoting cGAMP production to regulate the cGAS-STING axis by targeting cGAS positively.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

The Regulatory Network of Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway in Viral Evasion

et al. 2021

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Virus infection has been consistently threatening public health. The cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway is a critical defender to sense various pathogens and trigger innate immunity of mammalian cells. cGAS recognizes the pathogenic DNA in the cytosol and then synthesizes 2′3′-cyclic GMP-AMP (2′3′cGAMP). As the second messenger, cGAMP activates STING and induces the following cascade to produce type I interferon (IFN-I) to protect against infections. However, viruses have evolved numerous strategies to hinder the cGAS-STING signal transduction, promoting their immune evasion. Here we outline the current status of the viral evasion mechanism underlying the regulation of the cGAS-STING pathway, focusing on how post-transcriptional modifications, viral proteins, and non-coding RNAs involve innate immunity during viral infection, attempting to inspire new targets discovery and uncover potential clinical antiviral treatments.

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“…This is why new effective agents are still in demand. Due to the reports mentioned for the anti-SARS-CoV-2 properties of diverse antitumor active agents [69] , [70] , [71] , the targeted conjugates within the current study will be intended for anti-SARS-CoV-2 properties investigation. The successful clinical reports for treating the colon cancer patients with antiviral drugs alone or with antitumor drugs [72] also add good support for the aim of the present study directed towards optimizing new hits of dual functions as antitumor and anti-SARS-CoV-2 with safety properties against normal cells.…”

Section: Introductionmentioning

confidence: 99%