Development and evaluation of a host-targeted antiviral that abrogates herpes simplex virus replication through modulation of arginine-associated metabolic pathways

Sánchez, María Dulfary; Ochoa, Augusto C.; Foster, Timothy P.

doi:10.1016/j.antiviral.2016.05.009

Cited by 19 publications

(30 citation statements)

References 68 publications

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“…L-Arginine also serves as an essential role in viral replication. Herpes simplex viruses (HSV-1 and HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), and adenovirus require arginine to replicate [ 13 – 16 ]. In vitro studies have demonstrated a decrease in HSV 1-2 replication, cell-to-cell transmission, and virus-mediated cytopathic effects in mediums deficient in L-arginine [ 13 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

Recurrent Herpes Zoster Ophthalmicus Preceded by Anabolic Steroids and High-Dose L-Arginine

LoBue

Goldman

Giovane³

et al. 2020

Case Reports in Ophthalmological Medicine

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Purpose. To report a case of a 34-year-old male with recurrent herpes zoster ophthalmicus (HZO) preceded by a 6-week cycle of anabolic steroids and high-dose amino acid supplementation. Case Presentation. A 34-year-old man presented to our institution for left eye pain for one week associated with a vesicular rash in the V1 dermatome, respecting the midline. The patient had no significant past medical or past ocular history, including systemic immunosuppressive agents or HIV. However, prior to the onset of his symptoms the patient had completed a 6-week course of anabolic steroids including trenbolone, deca-durabolin, and testosterone as well as high-dose arginine supplementation averaging more than 40 grams a day. The best-corrected vision was 20/25 OS with slit-lamp examination remarkable for punctate staining and pseudodendrites at 6 o’clock, outside the visual axis. The patient was treated with oral acyclovir 800 mg five times a day for seven days along with prednisolone QID and moxifloxacin QID which was tapered over a month. Four months after resolution, the patient developed a recurrent HZO keratitis preceded by another cycle of anabolic steroids and amino acid supplementation. Conclusion. In vitro L-arginine supplementation has been associated with the proliferation and virulence of a variety of herpes viruses. Anabolic steroids have also been demonstrated by various studies to negatively affect cell-mediated immunity necessary to prevent viral infection. Thus, it is possible that anabolic steroids in conjunction with increased L-arginine intake may have precipitated a recurrent HZO in a previously healthy, immunocompetent individual.

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Section: Discussionmentioning

confidence: 99%

Recurrent Herpes Zoster Ophthalmicus Preceded by Anabolic Steroids and High-Dose L-Arginine

LoBue

Goldman

Giovane³

et al. 2020

Case Reports in Ophthalmological Medicine

View full text Add to dashboard Cite

show abstract

“…However, l -arginine also serves an essential role in viral replication. Herpes simplex viruses (HSV-1 and HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), and adenovirus require arginine to replicate 2, 3, 4, 5. One in vitro study demonstrated suppression of HSV replication within cells lacking arginine, a phenomenon which was rapidly reversed with the introduction of l -arginine 2 …”

Section: Discussionmentioning

confidence: 99%

“…In vitro experiments have shown arginine to be associated with the replication and virulence of a variety of viruses, including viruses from the herpes family 2, 3, 4, 5. These viruses are dependent on arginine-associated metabolic pathways in order to facilitate viral replication.…”

Section: Introductionmentioning

confidence: 99%

Recurrent herpes zoster ophthalmicus in a young, healthy individual taking high doses of l-Arginine

LoBue¹,

Tailor

Carlson

et al. 2019

American Journal of Ophthalmology Case Reports

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Purpose To report a case of a healthy, young male with recurrent herpes zoster ophthalmicus (HZO) and high-dose l -arginine supplementation. Observations A 39-year-old man presented to another institution with a HZO involving the right eye. He was treated with oral acyclovir with complete resolution. Four months later the patient had a recurrent HZO episode and was started again on oral acyclovir. After resolution of the episode, the patient was continued on 1 g of oral acyclovir daily as a prophylactic measure. He then presented to our institution for a second opinion. The patient was otherwise healthy, with no past medical history involving systemic immunosuppressant agents or HIV. However, the patient was an active weight lifter taking high doses of amino acids. A diet recall was performed prior to both HZO episodes, which calculated an average intake of 46.5 g of l -arginine a day. Examination revealed 20/40 best-corrected acuity, anterior stromal haze in the visual axis, and inferior superficial punctate keratitis in the right eye. The patient was treated for dry eye disease with punctual plugs and artificial tears. The patient was instructed to decrease all supplemental arginine consumption while continuing with oral acyclovir prophylaxis for one year. Conclusions and importance l -arginine is associated with the replication and virulence of a variety of viruses in vitro, including herpes simplex and varicella zoster. Although arginine consumption increased prior to the initial and recurrent HZO infection, further investigation needs to be performed to deem if a true association exists.

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“…As such, peg-arginase 1 extends the survival of mice undergoing bone marrow transplantation and delays the appearance of graft versus host diseases, whereas enhancing the growth of Listeria ( 97 , 161 ). Additionally, peg-arginase 1 exerts a potent anti-herpetic activity, blocking herpes simplex virus replication and virus-derived cytopathic effects in vitro ( 162 ). Arginine-catabolizing enzymes have a preclinical additive and/or synergistic effects with other treatments such as chemotherapy, radiotherapy, PI3K inhibitors, and autophagy regulators ( 149 ), and the clinical efficacy of these combinatorial approaches remains to be determined.…”

Section: Therapeutic Implications and Concluding Remarksmentioning

confidence: 99%

Arginine Metabolism in Myeloid Cells Shapes Innate and Adaptive Immunity

2017

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Arginine metabolism has been a key catabolic and anabolic process throughout the evolution of the immune response. Accruing evidence indicates that arginine-catabolizing enzymes, mainly nitric oxide synthases and arginases, are closely integrated with the control of immune response under physiological and pathological conditions. Myeloid cells are major players that exploit the regulators of arginine metabolism to mediate diverse, although often opposing, immunological and functional consequences. In this article, we focus on the importance of arginine catabolism by myeloid cells in regulating innate and adaptive immunity. Revisiting this matter could result in novel therapeutic approaches by which the immunoregulatory nodes instructed by arginine metabolism can be targeted.

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Development and evaluation of a host-targeted antiviral that abrogates herpes simplex virus replication through modulation of arginine-associated metabolic pathways

Cited by 19 publications

References 68 publications

Recurrent Herpes Zoster Ophthalmicus Preceded by Anabolic Steroids and High-Dose L-Arginine

Recurrent Herpes Zoster Ophthalmicus Preceded by Anabolic Steroids and High-Dose L-Arginine

Recurrent herpes zoster ophthalmicus in a young, healthy individual taking high doses of l-Arginine

Arginine Metabolism in Myeloid Cells Shapes Innate and Adaptive Immunity

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