Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy

Hakki, Morgan

doi:10.1007/s11899-020-00557-6

Cited by 35 publications

(37 citation statements)

References 151 publications

(166 reference statements)

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“…Of note, we are aware that in vitro studies report that LMV has a relatively low genetic barrier to resistance and generally support at least an additive effect (if not a synergistic one) of combining LMV with DNA polymerase inhibitors. 31 However, in our patient, due to GCV-resistance, intolerance to FOS and risk of CDV-related side effects, the use of LMV-based combination therapy was not possible and LMV was administrated as monotherapy.…”

Section: Discussionmentioning

confidence: 74%

Off-Label Use of Letermovir as Preemptive Anti-Cytomegalovirus Therapy in a Pediatric Allogeneic Peripheral Blood Stem Cell Transplant

Chiereghin¹,

Belotti²,

Borgatti³

et al. 2021

IDR

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Despite the effectiveness of the currently available antiviral drugs in treating cytomegalovirus (CMV) infection, high rates of adverse effects are associated with their use. Moreover, a problem of increasing importance is the emergence of drug-resistant CMV infection. Here, we describe the first case of off-label use of letermovir (LMV) as preemptive antiviral therapy, in a pediatric allogeneic peripheral blood stem cell transplant recipient with ganciclovir-resistant CMV infection who was intolerant to foscarnet and unable to achieve viral clearance after seven doses of cidofovir. After the administration of LMV, a gradual reduction in viral load was observed and within 6 weeks of LMV treatment, after more than 6 months of positive CMV-DNAemia, the patient cleared the infection. No adverse effects associated with LMV were observed during treatment. In this pediatric study case, the offlabel use of LMV for the treatment of CMV infection has been well tolerated and proved to be effective in leading to the suppression of viral replication.

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Section: Discussionmentioning

confidence: 74%

Off-Label Use of Letermovir as Preemptive Anti-Cytomegalovirus Therapy in a Pediatric Allogeneic Peripheral Blood Stem Cell Transplant

Chiereghin¹,

Belotti²,

Borgatti³

et al. 2021

IDR

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“…CHPK inhibitors are therefore promising candidates for alternative therapies to release the block in SAMHD1-mediated antiviral activity. The most advanced candidate, maribavir, was shown to potently reduce HCMV replication through inhibition of the viral kinase pUL97, and is currently under clinical investigation in a phase III study [ 141 , 142 ]. Thus, development of efficient strategies to block the various SAMHD1 evasion mechanisms such as the inhibition of viral kinases as well as SAMHD1-resistant NAs, will result in a higher efficacy and capability of antiviral therapies in the future.…”

Section: Discussionmentioning

confidence: 99%

SAMHD1 … and Viral Ways around It

Deutschmann

Gramberg

2021

Viruses

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The SAM and HD domain-containing protein 1 (SAMHD1) is a dNTP triphosphohydrolase that plays a crucial role for a variety of different cellular functions. Besides balancing intracellular dNTP concentrations, facilitating DNA damage repair, and dampening excessive immune responses, SAMHD1 has been shown to act as a major restriction factor against various virus species. In addition to its well-described activity against retroviruses such as HIV-1, SAMHD1 has been identified to reduce the infectivity of different DNA viruses such as the herpesviruses CMV and EBV, the poxvirus VACV, or the hepadnavirus HBV. While some viruses are efficiently restricted by SAMHD1, others have developed evasion mechanisms that antagonize the antiviral activity of SAMHD1. Within this review, we summarize the different cellular functions of SAMHD1 and highlight the countermeasures viruses have evolved to neutralize the restriction factor SAMHD1.

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“…Letermovir (2-[(4 S )-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-4 H -quinazolin-4-yl]acetic acid) ( Table 2 ) was discovered by high-throughput screening to have activity against CMV. Letermovir (trade name Prevymis™) was approved by FDA in 2017 for the prophylaxis of CMV infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant [ 100 ].…”

Section: Molecular Mechanisms Of Action Of Non-nucleoside Structured Compoundsmentioning

confidence: 99%

Non-nucleoside structured compounds with antiviral activity—past 10 years (2010–2020)

Denel-Bobrowska

Olejniczak

2022

European Journal of Medicinal Chemistry

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Nucleosides and their derivatives are a well-known and well-described class of compounds with antiviral activity. Currently, in the era of the COVID-19 pandemic, scientists are also looking for compounds not related to nucleosides with antiviral properties. This review aims to provide an overview of selected synthetic antiviral agents not associated to nucleosides developed against human viruses and introduced to preclinical and clinical trials as well as drugs approved for antiviral therapy over the last 10 years. The article describes for the first time the wide classification of such antiviral drugs and drug candidates and briefly summarizes the biological target and clinical applications of the compounds. The described compounds are arranged according to the antiviral mechanism of action. Knowledge of the drug's activity toward specific molecular targets may be the key to researching new antiviral compounds and repositioning drugs already approved for clinical use. The paper also briefly discusses the future directions of antiviral therapy. The described examples of antiviral compounds can be helpful for further drug development.

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Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy

Cited by 35 publications

References 151 publications

Off-Label Use of Letermovir as Preemptive Anti-Cytomegalovirus Therapy in a Pediatric Allogeneic Peripheral Blood Stem Cell Transplant

Off-Label Use of Letermovir as Preemptive Anti-Cytomegalovirus Therapy in a Pediatric Allogeneic Peripheral Blood Stem Cell Transplant

SAMHD1 … and Viral Ways around It

Non-nucleoside structured compounds with antiviral activity—past 10 years (2010–2020)

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