4′-Azidocytidine (R1479) inhibits henipaviruses and other paramyxoviruses with high potency

Hotard, Anne L.; He, Biao; Nichol, Stuart T.; Spiropoulou, Christina F.; Lo, Michael K.

doi:10.1016/j.antiviral.2017.06.011

Cited by 42 publications

(34 citation statements)

References 31 publications

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“…Recombinant reporter virus assays were performed as previously described [27,35]. In brief, 10 4 cells pretreated with serial dilutions of GRFT for 1 hour were infected with the above-mentioned reporter viruses (without washing) for 24-72 hours and then assayed either for GFP, GFP + cells, or for Renilla luciferase activity.…”

Section: Reporter Virus and Minigenome Assaysmentioning

confidence: 99%

Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge

Spengler

Krumpe

et al. 2020

The Journal of Infectious Diseases

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Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There is currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) is high-mannose oligosaccharide binding lectin that has shown in vivo broad-spectrum activity against viruses, including severe acute respiratory syndrome coronavirus, human immunodeficiency virus 1, hepatitis C virus, and Japanese encephalitis virus. In this study, we evaluated the in vitro antiviral activities of GRFT and its synthetic trimeric tandemer (3mG) against NiV and other viruses from 4 virus families. The 3mG had comparatively greater potency than GRFT against NiV due to its enhanced ability to block NiV glycoprotein-induced syncytia formation. Our initial in vivo prophylactic evaluation of an oxidation-resistant GRFT (Q-GRFT) showed significant protection against lethal NiV challenge in Syrian golden hamsters. Our results warrant further development of Q-GRFT and 3mG as potential NiV therapeutics.

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Section: Reporter Virus and Minigenome Assaysmentioning

confidence: 99%

Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge

Spengler

Krumpe

et al. 2020

The Journal of Infectious Diseases

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“…ddBCNAs (see sections "Poxviridae "and "Flaviviridae"; [99]) and the plant extract naphthoquinone droserone have anti-measles activities in vitro [87]. The nucleoside-analogue 4′-azidocytidine (R1479; balapiravir) was developed to inhibit HCV [108], paramyxoviruses, and filoviruses in vitro [63], but showed low efficacy and high toxicity in hepatitis C patients in early clinical trials [108].…”

Section: Paramyxoviridaementioning

confidence: 99%

Antivirals in medical biodefense

et al. 2020

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The viruses historically implicated or currently considered as candidates for misuse in bioterrorist events are poxviruses, filoviruses, bunyaviruses, orthomyxoviruses, paramyxoviruses and a number of arboviruses causing encephalitis, including alpha-and flaviviruses. All these viruses are of concern for public health services when they occur in natural outbreaks or emerge in unvaccinated populations. Recent events and intelligence reports point to a growing risk of dangerous biological agents being used for nefarious purposes. Public health responses effective in natural outbreaks of infectious disease may not be sufficient to deal with the severe consequences of a deliberate release of such agents. One important aspect of countermeasures against viral biothreat agents are the antiviral treatment options available for use in post-exposure prophylaxis. These issues were adressed by the organizers of the 16th Medical Biodefense Conference, held in Munich in 2018, in a special session on the development of drugs to treat infections with viruses currently perceived as a threat to societies or associated with a potential for misuse as biothreat agents. This review will outline the state-of-the-art methods in antivirals research discussed and provide an overview of antiviral compounds in the pipeline that are already approved for use or still under development.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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“…In a recent in-vitro study, favipiravir has been demonstrated its activity against viral replication and transcription in NiV and HeV (Dawes et al, 2018). R1479 (4 0 -azidocytidine) has also been reported to inhibit different members from Paramyxoviridae family (Hotard, He, Nichol, Spiropoulou, & Lo, 2017). However, despite these efforts for developing such inhibitors, no approved drugs are available yet for efficient use in humans.…”

Section: Introductionmentioning

confidence: 99%

Identifying potential entry inhibitors for emerging Nipah virus by molecular docking and chemical-protein interaction network

Pathania

Randhawa

Kumar

2019

Journal of Biomolecular Structure and Dynamics

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Nipah Virus (NiV) is a newly emergent paramyxovirus that has caused various outbreaks in Asian countries. Despite its acute pathogenicity and lack of approved therapeutics for human use, there is an urgent need to determine inhibitors against NiV. Hence, this work includes prospection of potential entry inhibitors by implementing an integrative structure-and network-based drug discovery approach. FDA-approved drugs were screened against attachment glycoprotein (NiV-G, PDB: 2VSM), one of the prime targets to inhibit viral entry, using a molecular docking approach that was benchmarked both on CCDC/ASTEX and known NIV-G inhibitor set. The predicted small molecules were prioritized on the basis of topological analysis of the chemical-protein interaction network, which was inferred by integrating the drug-target network, NiV-human interaction network, and human proteinprotein interaction network. A total of 17 drugs were predicted to be NiV-G inhibitors using molecular docking studies that were further prioritized to 3 novel leads À Nilotinib, Deslanoside and Acetyldigitoxin À on the basis of topological analysis of inferred chemical-protein interaction network. While Deslanoside and Acetyldigitoxin belong to an already known class of anti-NiV inhibitors, Nilotinib belongs to Benzenoids chemical class that has not been reported hitherto for developing anti-NiV inhibitors. These identified drugs are expected to be successful in further experimental evaluation and therefore could be used for anti-Nipah drug discovery. Apart, we also obtained various insights into the underlying chemical-protein interaction network, based on which several important network nodes were predicted. The applicability of our proposed approach was also demonstrated by prospecting for anti-NiV phytochemicals on an independent dataset.

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4′-Azidocytidine (R1479) inhibits henipaviruses and other paramyxoviruses with high potency

Cited by 42 publications

References 31 publications

Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge

Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge

Antivirals in medical biodefense

Identifying potential entry inhibitors for emerging Nipah virus by molecular docking and chemical-protein interaction network

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