New methylene blue derivatives suggest novel anti-orthopoxviral strategies

Priyamvada, Lalita; Burgado, Jillybeth; Baker-Wagner, Marissa; Kitaygorodskyy, Anatoliy; Olson, Victoria A.; Lingappa, Vishwanath R.; Satheshkumar, Panayampalli S.

doi:10.1016/j.antiviral.2021.105086

Cited by 20 publications

(19 citation statements)

References 35 publications

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“…The anti-proliferative compounds PAV-617 and PAV-951 had originally emerged from our CFPSA screen as inhibitors of viral capsid formation. The CFPSA model had been validated by demonstrating that hit antiviral assembly modulators display activity against infectious viruses in cell culture (U. F. Müller-Schiffmann et al, 2022;Priyamvada et al, 2021;Reed et al, 2021 617 is active against pox viruses in cell culture (see Fig. 2A for MPXV activity and Priyamvada et al, 2021 for chickenpox activity).…”

Section: Pav-951mentioning

confidence: 99%

“…The CFPSA model had been validated by demonstrating that hit antiviral assembly modulators display activity against infectious viruses in cell culture (U. F. Müller-Schiffmann et al, 2022;Priyamvada et al, 2021;Reed et al, 2021 617 is active against pox viruses in cell culture (see Fig. 2A for MPXV activity and Priyamvada et al, 2021 for chickenpox activity). The effective concentration for half maximal activity (EC50) of PAV-617 against MPXV is approximately 300 nM (See Fig.…”

Section: Pav-951mentioning

confidence: 99%

“…A collection of 300 structurally-diverse assembly modulators were assembled from hits demonstrating activity against capsid assembly in one or more viral family (V. . Antiviral assembly modulators from this collection have been validated against live virus in cell culture for multiple viral families including Retroviridae, Rhabdoviridae, Poxviridae, Adenoviridae, Herpesviridae, Paramyxoviridae, Coronaviridae, Orthomyxoviradae, and Picornaviridae (U. F. Müller-Schiffmann et al, 2022, 2021bPriyamvada et al, 2021;Reed et al, 2021). In two cases, Coronaviridae (porcine epidemic diarrhea virus) and Paramyxoviridae (respiratory syncytial virus), cellular antiviral activity has been confirmed in animal disease models (Müller-Schiffmann et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Small Molecule Protein Assembly Modulators with Pan-Cancer Therapeutic Efficacy

Lingappa¹,

Akintunde²,

Ewald³

et al. 2022

Preprint

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Two structurally-unrelated small molecule chemotypes, represented by compounds PAV-617 and PAV-951, with antiviral activity in cell culture against monkeypox virus (MPXV) and human immunodeficiency virus (HIV) respectively, were studied for anti-cancer efficacy. Each exhibited apparent pan-cancer cytotoxicity, reasonable pharmacokinetics, and non-toxicity in mice at active concentrations. Anti-tumor properties of each compound were validated in mouse xenografts against A549 human lung cancer. The targets of these compounds are unconventional: each binds to a different transient, energy-dependent multi-protein complex containing the protein KAP-1(TRIM28), an allosteric modulator known to broadly regulate mechanisms underlying viral and nonviral disease states including cancer. Treatment with these compounds alters the target multi-protein complexes in a manner consistent with allosteric modulation as their mechanism of action. These compounds appear to remove a block, crucial for cancer survival and progression, on the homeostatic linkage of uncontrolled cellular proliferation to apoptosis. These compounds may provide starting points for development of next-generation non-toxic, cancer therapeutics.

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Section: Pav-951mentioning

confidence: 99%

Section: Pav-951mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Small Molecule Protein Assembly Modulators with Pan-Cancer Therapeutic Efficacy

Lingappa¹,

Akintunde²,

Ewald³

et al. 2022

Preprint

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show abstract

“… 2 MB is a light-activated dye with demonstrated antimicrobial activity. 3 , 4 , 5 , 6 , 7 , 8 , 9 Photoactivated MB generates singlet oxygen, which damages viral nucleic acids and/or viral envelopes. 10 , 11 It is used to sterilize donor plasma before transfusion and is approved by the FDA for the treatment of methemoglobinemia.…”

Section: Introductionmentioning

confidence: 99%

Exploring inactivation of SARS-CoV-2, MERS-CoV, Ebola, Lassa, and Nipah viruses on N95 and KN95 respirator material using photoactivated methylene blue to enable reuse

Scholte

Kabra²,

Tritsch³

et al. 2022

American Journal of Infection Control

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“… 4 This light-activated dye is known to demonstrate antimicrobial activity. 8 , 9 , 10 , 11 , 12 , 13 , 14 Photoactivated MB generates singlet oxygen, which damages viral nucleic acids and/or viral envelopes. 15 , 16 It is used to sterilize donor plasma before transfusion and is approved by the FDA for the treatment of methemoglobinemia and in FDA-approved wound care dressings.…”

mentioning

confidence: 99%