Inhibition of HIV-1-Induced Cytopathogenicity, Syncytium Formation, and Virus-Cell Binding by Naphthalenedisulphonic Acids through Interaction with the Viral Envelope gp120 Glycoprotein

Baba, Masanori; Schols, Dominique; Mohan, P. Maruthi; Clercq, Erik De; Shigeta, Shirô

doi:10.1177/095632029300400405

Cited by 9 publications

(3 citation statements)

References 31 publications

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“…3): e.g., naphthalene sulfonates (330, 330a, 332-334) {i.e., 4,4Ј-[1,6hexanediylbis(carbonylamino)]bis(5-hydroxy-2,7-naphthalenedisulfonic acid) (335)}, stilbene sulfonates (87), Evans blue and various other sulfonated dyes (47,96,263,363,473), polystyrene sulfonate, polyanethole sulfonate, and polyvinyl sulfonate (331). These compounds would bind primarily to the viral envelope gp120 glycoprotein (28) and thus interfere with the interaction between the viral gp120 glycoprotein and the cellular CD4 receptor and block virus adsorption and virus-induced syncytium formation. Like the polysulfates, the polysulfonates inhibited not only the replication of HIV but also that of other enveloped viruses, i.e., CMV (24).…”

Section: Anti-hiv Agents Virus Adsorption Inhibitorsmentioning

confidence: 99%

Antiviral therapy for human immunodeficiency virus infections

1995

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Depending on the stage of their intervention with the viral replicative cycle, human immunodeficiency virus inhibitors could be divided into the following groups: (i) adsorption inhibitors (i.e., CD4 constructs, polysulfates, polysulfonates, polycarboxylates, and polyoxometalates), (ii) fusion inhibitors (i.e., plant lectins, succinylated or aconitylated albumins, and betulinic acid derivatives), (iii) uncoating inhibitors (i.e., bicyclams), (iv) reverse transcription inhibitors acting either competitively with the substrate binding site (i.e., dideoxynucleoside analogs and acyclic nucleoside phosphonates) or allosterically with a nonsubstrate binding site (i.e., non-nucleoside reverse transcriptase inhibitors), (v) integration inhibitors, (vi) DNA replication inhibitors, (vii) transcription inhibitors (i.e., antisense oligodeoxynucleotides and Tat antagonists), (viii) translation inhibitors (i.e., antisense oligodeoxynucleotides and ribozymes), (ix) maturation inhibitors (i.e., protease inhibitors, myristoylation inhibitors, and glycosylation inhibitors), and finally, (x) budding (assembly/release) inhibitors. Current knowledge, including the therapeutic potential, of these various inhibitors is discussed. In view of their potential clinical the utility, the problem of virus-drug resistance and possible strategies to circumvent this problem are also addressed.

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Section: Anti-hiv Agents Virus Adsorption Inhibitorsmentioning

confidence: 99%

Antiviral therapy for human immunodeficiency virus infections

1995

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“…Sulfonation of azo dyes increases their solubility in water and, at the same time, decreases their cellular absorption and enhances their urinary excretion in humans and animals. Sulfonated azo dyes can interact with positively charged amino acids, such as lysine and arginine, and possess antimicrobial activities (29)(30)(31)(32)(33). Some azo dyes, called food azo dyes, have been authorized to be used as additives in the food and beverage industry since the nineteenth century.…”

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confidence: 99%

In Vitro and In Vivo Inhibition of the Infectivity of Human Enterovirus 71 by a Sulfonated Food Azo Dye, Brilliant Black BN

Meng

Jia

Wong

et al. 2019

J Virol

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Hand, foot, and mouth disease (HFMD), a highly contagious disease in children, is caused by human enteroviruses, including enterovirus 71 (EV71), coxsackievirus A16 (CVA16), and coxsackievirus A6 (CVA6). Although HFMD is usually mild and self-limiting, EV71 infection occasionally leads to fatal neurological disorders. Currently, no commercial antiviral drugs for HFMD treatment are available. Here, numerous sulfonated azo dyes, widely used as food additives, were identified as having potent antiviral activities against human enteroviruses. Among them, brilliant black BN (E151) was able to inhibit all EV71, CVA16, and CVA6 strains tested. In rhabdomyosarcoma cells, the 50% inhibitory concentrations of the dye E151 for various strains of EV71 ranged from 2.39 M to 28.12 M, whereas its 50% cytotoxic concentration was 1,870 M. Food azo dyes, including E151, interacted with the vertex of the 5-fold axis of EV71 and prevented viral entry. Their efficacy in viral inhibition was regulated by amino acids at VP1-98, VP1-145, and/or VP1-246. Dye E151 not only prevented EV71 attachment but also eluted attached viruses in a concentration-dependent manner. Moreover, E151 inhibited the interaction between EV71 and its cellular uncoating factor cyclophilin A. In vivo studies demonstrated that E151 at a dose of 200 mg/kg of body weight/day given on the initial 4 days of challenge protected AG129 mice challenged with 10ϫ the 50% lethal dose of wild-type EV71 isolates. Taken together, these data highlight E151 as a promising antiviral agent against EV71 infection. IMPORTANCE Human enterovirus 71 (EV71) is one of the causative agents of hand, foot, and mouth disease in children and is responsible for thousands of deaths in the past 20 years. Food azo dyes have been widely used since the nineteenth century; however, their biological effects on humans and microbes residing in humans are poorly understood. Here, we discovered that one of these dyes, brilliant black BN (E151), was particularly effective in inhibiting the infectivity of EV71 in both cell culture and mouse model studies. Mechanistic studies demonstrated that these sulfonated dyes mainly competed with EV71 attachment factors for viral binding to block viral attachment/entry to host cells. As no commercial antiviral drugs against EV71 are currently available, our findings open an avenue to exploit the development of permitted food dye E151 as a potential anti-EV71 agent. KEYWORDS AG129 mouse, antiviral agent, food azo dye, hand foot and mouth disease, human enterovirus, sulfonate, virus attachment factors, virus entry H and, foot and mouth disease (HFMD), a common and highly contagious disease in children, is caused by human enteroviruses, including enterovirus 71 (EV71), coxsackievirus A16 (CVA16), and coxsackievirus A6 (CVA6). The clinical features of HFMD include rashes on the hands and feet, buccal ulcerative lesions, fatigue, fever, RESULTSInhibitory effects of food dyes on the propagation of EV71-GFP. Eleven widely used food dyes were screened for their potency in inhi...

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“…The solid obtained after evaporation of the appropriate fractions was dissolved in minimum volume of deionized water and precipitated by adding excess acetone (0.098 g). An analytically pure sample was prepared by twice reprecipitating the product from its concentrated methanolic solution with ether: mp 250-252 °C dec; IR 3421, 3408, 1655, 1587, 1458, 1198, 1043 cm*1; NMR 17.96 (s, 3H, exchangeable with D20), 9.15 (br s, 3H, exchangeable with D20), 7.62 (s, 3H), 7.49 4,4'-[l,2-Ethanediylbis(carbonylamino)]bis(l-naphthalenesulfonic acid) (7). 4-Amino-l-naphthalenesulfonic acid (0.300 g, 1.345 mmol) was heated to 100 °C for 15 min, succinyl chloride (0.12 g, 0.774 mmol) was added, and the mixture was stirred for another 15 min.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Structure-activity relationship studies with symmetric naphthalenesulfonic acid derivatives. Synthesis and influence of spacer and naphthalenesulfonic acid moiety on anti-HIV-1 activity

Mohan¹,

Wong²,

Verma³

et al. 1993

J. Med. Chem.

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Symmetric bis(naphthalenesulfonic acid) derivatives containing a variety of spacers have been synthesized and evaluated for anti-HIV-1 activity in four assay systems. In the assay that measured inhibition of HIV-1-induced cytopathogenicity using a laboratory strain (HTLV-IIIB), a hexamethylene and octamethylene spacer derivative of 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid emerged as the most potent derivatives. The hexamethylene spacer analog exhibited an in vitro therapeutic index that was > 120. Selected derivatives were tested in the giant cell formation assay. In this assay, the most potent derivative was, again, the hexamethylene compound. Evaluation of selected derivatives against a clinical isolate of HIV-1 (HE strain) revealed that the hexamethylene derivative was the most potent compound. In the assay that measured the inhibition of HIV-1-induced cytopathogenesis in human peripheral blood lymphocytes, the hexamethylene compound emerged as the most active derivative, demonstrating a 50% inhibitory concentration of 1.3 microM. These studies clearly demonstrate that certain naphthalenesulfonic acid moieties when coupled to specific spacers were synergistic in producing anti-HIV-1 activity at nontoxic concentrations. In the 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid series, shortening of the spacer length, preferably with a flexible polymethylene chain, was highly beneficial for increasing anti-HIV-1 potency.

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Inhibition of HIV-1-Induced Cytopathogenicity, Syncytium Formation, and Virus-Cell Binding by Naphthalenedisulphonic Acids through Interaction with the Viral Envelope gp120 Glycoprotein

Cited by 9 publications

References 31 publications

Antiviral therapy for human immunodeficiency virus infections

Antiviral therapy for human immunodeficiency virus infections

In Vitro and In Vivo Inhibition of the Infectivity of Human Enterovirus 71 by a Sulfonated Food Azo Dye, Brilliant Black BN

Structure-activity relationship studies with symmetric naphthalenesulfonic acid derivatives. Synthesis and influence of spacer and naphthalenesulfonic acid moiety on anti-HIV-1 activity

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