A Cutting‐Edge View on the Current State of Antiviral Drug Development

Clercq, Erik De

doi:10.1002/med.21281

Cited by 51 publications

(47 citation statements)

References 152 publications

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“…Unlike most antiviral nucleoside analogs48 and despite the presence of the 3′-OH radical in its chemical structure37, sofosbuvir acts as a chain terminator. To impair the incorporation of the incoming nucleotides, the 2′-F radical disrupts the hydrogen bonding network37.…”

Section: Discussionmentioning

confidence: 99%

The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication

Sacramento¹,

Melo²,

Freitas³

et al. 2017

Sci Rep

188

160

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Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues. Sofosbuvir inhibited ZIKV replication in different cellular systems, such as hepatoma (Huh-7) cells, neuroblastoma (SH-Sy5y) cells, neural stem cells (NSC) and brain organoids. In addition to the direct inhibition of the viral RNA polymerase, we observed that sofosbuvir also induced an increase in A-to-G mutations in the viral genome. Together, our data highlight a potential secondary use of sofosbuvir, an anti-HCV drug, against ZIKV.

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Section: Discussionmentioning

confidence: 99%

The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication

Sacramento¹,

Melo²,

Freitas³

et al. 2017

Sci Rep

188

160

View full text Add to dashboard Cite

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“…A relatively recently introduced compound, brincidofovir (1-O-hexadecyloxypropyl-cidofovir; formerly known as CMX001), is an orally bioavailable lipid conjugate of cidofovir displaying substantially less nephrotoxicity than that of the parent drug. The compound has been employed successfully for treatment of viral infections in allo-HSCT recipients and other settings (241)(242)(243), but mutations conferring resistance may arise (244). Preliminary observations on the efficacy against HAdV showed promising results (245,246), and clinical development of the drug is currently ongoing.…”

Section: Antiviral Drugsmentioning

confidence: 99%

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

2014

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SUMMARY Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical challenges pertaining to diagnostics and treatment. The growing number of HAdV types identified by genomic analysis, as well as the improved understanding of the sites of viral persistence and reactivation, requires continuous adaptions of diagnostic approaches to facilitate timely detection and monitoring of HAdV infections. In view of the clinical relevance of life-threatening HAdV diseases in the immunocompromised setting, there is an urgent need for highly effective treatment modalities lacking major side effects. The present review summarizes the recent progress in the understanding and management of HAdV infections.

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“…In addition, although this raises obvious ethical problems, it would be desirable to extend the current knowledge through further investigations involving the use of TDF alone and/or with the occurrence of nephrotoxicity as primary endpoint. TAF, the new oral prodrug of tenofovir, has shown promising results in terms of renal safety [20,23,56,57,72,73], although more data are needed to strengthen this evidence in chronic HBV infection [58].…”

Section: Discussionmentioning

confidence: 98%

The case of chronic hepatitis B treatment with tenofovir: an update for nephrologists

et al. 2015

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Tenofovir is a nucleotide acting both as an inhibitor of human immunodeficiency (HIV) reverse transcriptase and as a competitor for hepatitis B virus (HBV) RNA-directed DNA polymerase. Approved worldwide in 2001, tenofovir is used as a component of highly active antiretroviral therapy (HAART) in patients with HIV infection. Since 2008, it has also been indicated for treatment of chronic HBV infection or HIV/HBV co-infection. The aim of the treatment consists in suppressing viral replication, thus reducing hepatic complications and improving patient survival. Furthermore, tenofovir could represent an effective therapeutic option in lamivudine-resistant HBV patients. Tenofovir is eliminated unchanged through urine via glomerular filtration (80%) and proximal tubular secretion (20%). Thus, alterations in renal clearance may interfere with tenofovir pharmacokinetics and systemic drug concentrations, modifying the therapeutic response. Hence, a renal overload of tenofovir in patients with a pre-existing kidney impairment could result in a worsening of renal function. Following a brief introduction on HBV infection and its therapeutic options, we review the latest evidence, to our knowledge, on renal toxicity of tenofovir in HBV patients and on drug management.

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A Cutting‐Edge View on the Current State of Antiviral Drug Development

Cited by 51 publications

References 152 publications

The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication

The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

The case of chronic hepatitis B treatment with tenofovir: an update for nephrologists

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