Inhibition of Myosin Light Chain Kinase Can be Targeted for the Development of New Therapies against Herpes Simplex Virus Type-1 Infection

Antoine, Thessicar E.; Shukla, Deepak

doi:10.3851/imp2661

Cited by 17 publications

(20 citation statements)

References 48 publications

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“…Herpes simplex virus type 1 (HSV-1) is a world-spread pathogen which infects over a half of adult humans, resulting in diverse ocular, oral, and genital manifestations (Antoine and Shukla, 2014; Lathe and Haas, 2016). Currently, we still have no effective means for treating HSV-1.…”

Section: Nm II In Microbial-triggered Discordsmentioning

confidence: 99%

“…Moreover, treatment of the murine model with ML-7 before viral inoculation could significantly inhibit HSV-1 infection and improve survival rate. Therefore, both ML-7 and ML-9 are used as novel therapies to block HSV-1 infection by inhibiting MLCK activity (Antoine and Shukla, 2014).…”

Section: Nm II Inhibitors With Potential Drug Applicationmentioning

confidence: 99%

“…This inhibitor specially binds to the ATPase site of NM II heads and decreases the phosphate release rate, thereby suppressing the activity of NM II (Kovács et al, 2004). In recent years, Blebbistatin has been widely applied in many viral researches including EHV-1 (Cymerys et al, 2016), HSV-1 (Antoine and Shukla, 2014), HIV (Kadiu and Gendelman, 2011), and KSHV (Valiya Veettil et al, 2010). For example, Blebbistatin interferes with the KSHV and HSV-1 internalization process to inhibit the entry of virions (Valiya Veettil et al, 2010; Antoine and Shukla, 2014).…”

Section: Nm II Inhibitors With Potential Drug Applicationmentioning

confidence: 99%

“…In recent years, Blebbistatin has been widely applied in many viral researches including EHV-1 (Cymerys et al, 2016), HSV-1 (Antoine and Shukla, 2014), HIV (Kadiu and Gendelman, 2011), and KSHV (Valiya Veettil et al, 2010). For example, Blebbistatin interferes with the KSHV and HSV-1 internalization process to inhibit the entry of virions (Valiya Veettil et al, 2010; Antoine and Shukla, 2014). Additionally, Blebbistatin could also inhibit EHV-1 intercellular spread (Cymerys et al, 2016).…”

Section: Nm II Inhibitors With Potential Drug Applicationmentioning

confidence: 99%

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Non-muscle Myosin II: Role in Microbial Infection and Its Potential as a Therapeutic Target

et al. 2019

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Currently, the major measures of preventing and controlling microbial infection are vaccinations and drugs. However, the appearance of drug resistance microbial mounts is main obstacle in current anti-microbial therapy. One of the most ubiquitous actin-binding proteins, non-muscle myosin II (NM II) plays a crucial role in a wide range of cellular physiological activities in mammals, including cell adhesion, migration, and division. Nowadays, growing evidence indicates that aberrant expression or activity of NM II can be detected in many diseases caused by microbes, including viruses and bacteria. Furthermore, an important role for NM II in the infection of some microbes is verified. Importantly, modulating the expression of NM II with small hairpin RNA (shRNA) or the activity of it by inhibitors can affect microbial-triggered phenotypes. Therefore, NM II holds the promise to be a potential target for inhibiting the infection of microbes and even treating microbial-triggered discords. In spite of these, a comprehensive view on the functions of NM II in microbial infection and the regulators which have an impact on the roles of NM II in this context, is still lacking. In this review, we summarize our current knowledge on the roles of NM II in microbial-triggered discords and provide broad insights into its regulators. In addition, the existing challenge of investigating the multiple roles of NM II in microbial infection and developing NM II inhibitors for treating these microbial-triggered discords, are also discussed.

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Section: Nm II In Microbial-triggered Discordsmentioning

confidence: 99%

Section: Nm II Inhibitors With Potential Drug Applicationmentioning

confidence: 99%

Section: Nm II Inhibitors With Potential Drug Applicationmentioning

confidence: 99%

Section: Nm II Inhibitors With Potential Drug Applicationmentioning

confidence: 99%

See 2 more Smart Citations

Non-muscle Myosin II: Role in Microbial Infection and Its Potential as a Therapeutic Target

et al. 2019

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“…Another study designed synthetic peptides specific to the glycoproteins gD and gG and showed that these peptides can effectively recognize HSV-2 antibodies and hence may be used for serodiagnostic assays 132 . Because HSV utilizes the cytoskeleton filaments and kinases during its entry, a recent study showed that blocking the myosin light chain kinase (MLCK) with inhibitors such as blebbistatin significantly reduces HSV infection 133 , providing new evidence for potential targets in blocking HSV infections. The advent of nanoparticles in drug delivery was successful, owing to their ability to provide sustained or extended delivery of drugs at a local site.…”

Section: Treatment and Preventionmentioning

confidence: 99%

Genital Herpes: Insights into Sexually Transmitted Infectious Disease

Jaishankar

Shukla

2016

MIC

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Etiology, transmission and protection: Herpes simplex virus-2 (HSV-2) is a leading cause of sexually transmitted infections with recurring manifestations throughout the lifetime of infected hosts. Currently no effective vaccines or prophylactics exist that provide complete protection or immunity from the virus, which is endemic throughout the world. Pathology/Symptomatology: Primary and recurrent infections result in lesions and inflammation around the genital area and the latter accounts for majority of genital herpes instances. Immunocompromised patients including neonates are susceptible to additional systemic infections including debilitating consequences of nervous system inflammation. Epidemiology, incidence and prevalence: More than 500 million people are infected worldwide and most reported cases involve the age groups between 16-40 years, which coincides with an increase in sexual activity among this age group. While these numbers are an estimate, the actual numbers may be underestimated as many people are asymptomatic or do not report the symptoms. Treatment and curability: Currently prescribed medications, mostly nucleoside analogs, only reduce the symptoms caused by an active infection, but do not eliminate the virus or reduce latency. Therefore, no cure exists against genital herpes and infected patients suffer from periodic recurrences of disease symptoms for their entire lives. Molecular mechanisms of infection: The last few decades have generated many new advances in our understanding of the mechanisms that drive HSV infection. The viral entry receptors such as nectin-1 and HVEM have been identified, cytoskeletal signaling and membrane structures such as filopodia have been directly implicated in viral entry, host motor proteins and their viral ligands have been shown to facilitate capsid transport and many host and HSV proteins have been identified that help with viral replication and pathogenesis. New understanding has emerged on the role of autophagy and other innate immune mechanisms that are subverted to enhance HSV pathogenesis. This review summarizes our current understanding of HSV-2 and associated diseases and available or upcoming new treatments.

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Myosin motors on the pathway of viral infections

2022

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Molecular motors are microscopic machines that use energy from adenosine triphosphate (ATP) hydrolysis to generate movement. While kinesins and dynein are molecular motors associated with microtubule tracks, myosins bind to and move on actin filaments. Mammalian cells express several myosin motors. They power cellular processes such as endo‐ and exocytosis, intracellular trafficking, transcription, migration, and cytokinesis. As viruses navigate through cells, they may take advantage or be hindered by host components and machinery, including the cytoskeleton. This review delves into myosins' cell roles and compares them to their reported functions in viral infections. In most cases, the previously described myosin functions align with their reported role in viral infections, although not in all cases. This opens the possibility that knowledge obtained from studying myosins in viral infections might shed light on new physiological roles for myosins in cells. However, given the high number of myosins expressed and the variety of viruses investigated in the different studies, it is challenging to infer whether the interactions found are specific to a single virus or can be applied to other viruses with the same characteristics. We conclude that the participation of myosins in viral cycles is still a largely unexplored area, especially concerning unconventional myosins.

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Inhibition of Myosin Light Chain Kinase Can be Targeted for the Development of New Therapies against Herpes Simplex Virus Type-1 Infection

Abstract: We provide new evidence that NM-IIA and MLCK can be used as effective antiviral targets against ocular herpes.

Cited by 17 publications

References 48 publications

Non-muscle Myosin II: Role in Microbial Infection and Its Potential as a Therapeutic Target

Non-muscle Myosin II: Role in Microbial Infection and Its Potential as a Therapeutic Target

Genital Herpes: Insights into Sexually Transmitted Infectious Disease

Myosin motors on the pathway of viral infections

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