Broad-Spectrum
            <i>In Vitro</i>
            Antiviral Activity of ODBG-P-RVn: An Orally-Available, Lipid-Modified Monophosphate Prodrug of Remdesivir Parent Nucleoside (GS-441524)

Lo, Michael K.; Shrivastava-Ranjan, Punya; Chatterjee, Payel; Flint, Mike; Beadle, James R.; Valiaeva, Nadejda; Murphy, Joyce; Schooley, Robert T.; Hostetler, Karl Y.; Spiropoulou, Christina F.

doi:10.1128/spectrum.01537-21

Cited by 27 publications

(23 citation statements)

References 22 publications

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“…We have repeatedly shown that remdesivir efficiently inhibits MV dissemination at half-maximal inhibitory concentrations below 180 nM, regardless if wild-type-based viruses or vaccine-strain-based viruses were used. In line with this, Lo et al estimated the IC 50 of remdesivir against MV infection in HeLa cells at 37 nM, in VeroE6 cells at 5 µM, in NCl-H358 cells at 25 nM and in HSAEC1-KT cells at 63 nM, using an rMV EZ EGFP(3) reporter-based assay [41,42]. Our assay resembles the early dissemination phase and mimics in vivo cell-to-cell viral spread instead of cell-free virus production.…”

Section: Discussionmentioning

confidence: 61%

“…Ribavirin and ribavirin-derivatives and -analogs [33][34][35][36][37][38][39][40] Ring-expanded purine nucleosides [34] Remdesivir [41,42] Favipiravir (T-705) [43,44] Derivatives of R1479 [45] Pyrazofurin [36] 3-Deazaguanine and its carbocyclic analog [36,38,40] 6-Azauridine [36] 5'-nor carbocyclic adenosine analogues [46] L-dideoxy bicyclic nucleoside analogs [47] Non-nucleoside polymerase inhibitors AS136a [48,49] ERDRP-0519 [49][50][51][52] GHP-88309 [53] Fusion and entry inhibitors Peptide inhibitors Z-D-Phe-L-Phe-L-Gly (FIP) [54][55][56][57][58] HRC-based peptides: M1, M2, M3, M4, M1EK, M2EK, M3EK, M4EK [59] HRC-lipopeptides [60][61][62][63][64] FIP-lipopeptides [64] FIP-HRC-lipopeptides [64] Nonpeptidic small molecules [65] 16677 [66] 3G [63,67] AS-48 [56][57]…”

Section: Nucleoside Analogsmentioning

confidence: 99%

“…Hallé [35] Mantooth [35] McClellan [35] Vero [68] VeroE6 [42,53] Vero-humanSLAM [44,51,53,60] Vero-dogSLAM [70] CHO/SLAM [56] CHO/CD46 [56] CHO/PVRL4 [56] HeLa [41] NCI-H358 [42,45] HSAEC1-KT [42] NT2 [69] HEK293T [69] MV Edmonston-derived rMV-Edm-(E)GFP [41,42,44,45,56,68] rMV-Moraten-Luciferase [70] rMV-NanolucPEST [51,53] MV wild-type-derived rMV-IC323-eGFP [56,60] rMV-IC323-Luciferase [70] Adapted MV-derived rMVHcRed-CAMH [69] rMV-EGFP-CAMH [69] Plaque assay (Serially diluted) compounds added to overlay medium. After fixation, plaques are visualized with crystal violet, neutral red or fluorescently (reporter virus or immunostaining) and used to evaluate compound potency.…”

Section: Sspe Virusesmentioning

confidence: 99%

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Repurposing an In Vitro Measles Virus Dissemination Assay for Screening of Antiviral Compounds

Schmitz

Lange

Gommers

et al. 2022

Viruses

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Measles virus (MV) is a highly contagious respiratory virus responsible for outbreaks associated with significant morbidity and mortality among children and young adults. Although safe and effective measles vaccines are available, the COVID-19 pandemic has resulted in vaccination coverage gaps that may lead to the resurgence of measles when restrictions are lifted. This puts individuals who cannot be vaccinated, such as young infants and immunocompromised individuals, at risk. Therapeutic interventions are complicated by the long incubation time of measles, resulting in a narrow treatment window. At present, the only available WHO-advised option is treatment with intravenous immunoglobulins, although this is not approved as standard of care. Antivirals against measles may contribute to intervention strategies to limit the impact of future outbreaks. Here, we review previously described antivirals and antiviral assays, evaluate the antiviral efficacy of a number of compounds to inhibit MV dissemination in vitro, and discuss potential application in specific target populations. We conclude that broadly reactive antivirals could strengthen existing intervention strategies to limit the impact of measles outbreaks.

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Section: Discussionmentioning

confidence: 61%

Section: Nucleoside Analogsmentioning

confidence: 99%

Section: Sspe Virusesmentioning

confidence: 99%

See 1 more Smart Citation

Repurposing an In Vitro Measles Virus Dissemination Assay for Screening of Antiviral Compounds

Schmitz

Lange

Gommers

et al. 2022

Viruses

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“… 23 Another promising orally bioavailable remdesivir‐like prodrug candidate is ODBG‐P‐RVn. 24 It also showed efficacy on five different cell lines. 25 Along with IV remdesivir, oral Rvn prodrugs would be game‐changers in the early treatment of Covid‐19.…”

Section: Remdesivirmentioning

confidence: 93%

Comparative evaluation of authorized drugs for treating Covid‐19 patients

Islam

Hasan

Rahman

et al. 2022

Health Science Reports

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Background and Aims Vaccines are the first line of defense against coronavirus disease 2019 (Covid‐19). However, the antiviral drugs provide a new tool to fight the Covid‐19 pandemic. Here we aimed for a comparative evaluation of authorized drugs for treating Covid‐19 patients. Methods We searched in PubMed and Google Scholar using keywords and terms such as Covid, SARS‐CoV‐2, Coronavirus disease 2019, therapeutic management, hospitalized Covid‐19 patients, Covid‐19 treatment. We also gathered information from reputed newspapers, web portals, and websites. We thoroughly observed, screened, and included the studies relevant to our inclusion criteria. We included only the United States Food and Drug Administration (FDA) authorized drugs for this review. Results We found that molnupiravir and paxlovid are available for oral use, and remdesivir is for only hospitalized patients. Paxlovid is a combination of nirmatrelvir and ritonavir, nirmatrelvir is a protease inhibitor (ritonavir increases the concentration of nirmatrelvir), and the other two (remdesivir and molnupiravir) are nucleoside analog prodrugs. Remdesivir and molnupiravir doses do not need to adjust in renal and hepatic impairment. However, the paxlovid dose adjustment is required for mild to moderate renal or hepatic impaired patients. Also, the drug is not allowed for Covid‐19 patients with severe renal or hepatic impairment. Preliminary studies showed oral antiviral drugs significantly reduce hospitalization or death among mild to severe patients. Moreover, the US FDA has approved four monoclonal antibodies for Covid‐19 treatment. Studies suggest that these drugs would reduce the risk of hospitalization or severity of symptoms. World Health Organization strongly recommended the use of corticosteroids along with other antiviral drugs for severe or critically hospitalized patients. Conclusion All authorized drugs are effective in inhibiting viral replication for most SARS‐CoV‐2 variants. Therefore, along with vaccines, these drugs might potentially aid in fighting the Covid‐19 pandemic.

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“…Lo et al. reported an oral ODBG-P-RVn (lipid-modified monophosphate prodrug of the remdesivir parent nucleoside GS-441524), which showed a 20-fold higher antiviral activity than GS-441524 and had an activity very similar to that of remdesivir using primary-like human small airway epithelial cells ( 69 ).…”

Section: Antiviral Effect Of Remdesivir Derivativesmentioning

confidence: 99%

Remdesivir and Its Combination With Repurposed Drugs as COVID-19 Therapeutics

Chatterjee

Thakur

2022

Front. Immunol.

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The SARS-CoV-2 virus needs multiple copies for its multiplication using an enzyme RNA-dependent RNA polymerase (RdRp). Remdesivir inhibits viral RdRp, controls the multiplication of the virus, and protects patients. However, treatment of COVID-19 with remdesivir involves adverse effects. Many ongoing clinical trials are exploring the potential of the combination of remdesivir with repurposed drugs by targeting multiple targets of virus and host human simultaneously. Better results were obtained with the remdesivir–baricitinib combination treatment for COVID-19 compared to the treatment with remdesivir alone. Notably, recovery from COVID-19 was found to be 8 days less via the remdesivir–baricitinib combination treatment as compared to remdesivir treatment alone. Furthermore, the mortality rate via the remdesivir–baricitinib combination treatment was lower compared to the remdesivir-only treatment. Remdesivir targets the SARS-CoV-2 enzyme while baricitinib targets the host human enzyme. Simultaneously, remdesivir and baricitinib as a combination inhibit their target viral RdRp and human Janus kinase, respectively. Ongoing trials for the combination of drugs will suggest in the future whether they may reduce the recovery time, reduce the mortality rate, and improve patient clinical status for noninvasive ventilation. In the future, simultaneously targeting virus replication enzymes and host human kinases may be the strategy for SARS-CoV-2 therapeutics.

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Broad-Spectrum In Vitro Antiviral Activity of ODBG-P-RVn: An Orally-Available, Lipid-Modified Monophosphate Prodrug of Remdesivir Parent Nucleoside (GS-441524)

Cited by 27 publications

References 22 publications

Repurposing an In Vitro Measles Virus Dissemination Assay for Screening of Antiviral Compounds

Repurposing an In Vitro Measles Virus Dissemination Assay for Screening of Antiviral Compounds

Comparative evaluation of authorized drugs for treating Covid‐19 patients

Remdesivir and Its Combination With Repurposed Drugs as COVID-19 Therapeutics

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