Putative targeting by BX795 causes decrease in protein kinase C protein levels and inhibition of HSV1 infection

Rahul K. Suryawanshi; Chandrashekhar D. Patil; David Wu; Pritam Kumar Panda; Sudhanshu Kumar Singh; Ipsita Volety; Rajeev Ahuja; Yogendra Kumar Mishra; Deepak Shukla

doi:10.1016/j.antiviral.2022.105454

Putative targeting by BX795 causes decrease in protein kinase C protein levels and inhibition of HSV1 infection

Rahul K. Suryawanshi, Chandrashekhar D. Patil, David Wu, Pritam Kumar Panda, Sudhanshu Kumar Singh, Ipsita Volety, Rajeev Ahuja, Yogendra Kumar Mishra, Deepak Shukla

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Herpes simplex virus type-1 (HSV1) exploits cellular machinery for its own replicative advantage. Current treatment modalities against HSV1 cause toxicity and drug resistance issues. In the search for alternative forms of treatment, we have uncovered a small molecule, BX795, as a candidate drug with strong antiviral potential owing to its multitargeted mode of action. In this study, we show that in addition to a previously known mechanism of action, BX795 can directly interact with the proviral host factor protein kinase C (PKC) in silico. When administered to HSV1 or mock infected human corneal epithelial (HCE) cells, BX795 significantly reduces the protein level and perinuclear localization of proviral PKC-α and PKC-ζ isoforms. This activity closely mimics that of a known PKC inhibitor, Bisindolylmaleimide I (BIM I), which also inhibits viral replication. Taken together our studies demonstrate a previously unknown mechanism by which BX795 exerts its antiviral potential.

Original language	English
Article number	105454
Journal	Antiviral Research
Volume	208
DOIs	https://doi.org/10.1016/j.antiviral.2022.105454
State	Published - 1 Dec 2022
Externally published	Yes

Keywords

Antiviral
BX795
Herpesvirus
Mechanism
Protein kinase C

ASJC Scopus subject areas

Pharmacology
Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.antiviral.2022.105454

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title = "Putative targeting by BX795 causes decrease in protein kinase C protein levels and inhibition of HSV1 infection",

abstract = "Herpes simplex virus type-1 (HSV1) exploits cellular machinery for its own replicative advantage. Current treatment modalities against HSV1 cause toxicity and drug resistance issues. In the search for alternative forms of treatment, we have uncovered a small molecule, BX795, as a candidate drug with strong antiviral potential owing to its multitargeted mode of action. In this study, we show that in addition to a previously known mechanism of action, BX795 can directly interact with the proviral host factor protein kinase C (PKC) in silico. When administered to HSV1 or mock infected human corneal epithelial (HCE) cells, BX795 significantly reduces the protein level and perinuclear localization of proviral PKC-α and PKC-ζ isoforms. This activity closely mimics that of a known PKC inhibitor, Bisindolylmaleimide I (BIM I), which also inhibits viral replication. Taken together our studies demonstrate a previously unknown mechanism by which BX795 exerts its antiviral potential.",

keywords = "Antiviral, BX795, Herpesvirus, Mechanism, Protein kinase C",

author = "Suryawanshi, {Rahul K.} and Patil, {Chandrashekhar D.} and David Wu and Panda, {Pritam Kumar} and Singh, {Sudhanshu Kumar} and Ipsita Volety and Rajeev Ahuja and Mishra, {Yogendra Kumar} and Deepak Shukla",

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year = "2022",

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day = "1",

doi = "10.1016/j.antiviral.2022.105454",

language = "English",

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T1 - Putative targeting by BX795 causes decrease in protein kinase C protein levels and inhibition of HSV1 infection

AU - Suryawanshi, Rahul K.

AU - Patil, Chandrashekhar D.

AU - Wu, David

AU - Panda, Pritam Kumar

AU - Singh, Sudhanshu Kumar

AU - Volety, Ipsita

AU - Ahuja, Rajeev

AU - Mishra, Yogendra Kumar

AU - Shukla, Deepak

PY - 2022/12/1

Y1 - 2022/12/1

N2 - Herpes simplex virus type-1 (HSV1) exploits cellular machinery for its own replicative advantage. Current treatment modalities against HSV1 cause toxicity and drug resistance issues. In the search for alternative forms of treatment, we have uncovered a small molecule, BX795, as a candidate drug with strong antiviral potential owing to its multitargeted mode of action. In this study, we show that in addition to a previously known mechanism of action, BX795 can directly interact with the proviral host factor protein kinase C (PKC) in silico. When administered to HSV1 or mock infected human corneal epithelial (HCE) cells, BX795 significantly reduces the protein level and perinuclear localization of proviral PKC-α and PKC-ζ isoforms. This activity closely mimics that of a known PKC inhibitor, Bisindolylmaleimide I (BIM I), which also inhibits viral replication. Taken together our studies demonstrate a previously unknown mechanism by which BX795 exerts its antiviral potential.

AB - Herpes simplex virus type-1 (HSV1) exploits cellular machinery for its own replicative advantage. Current treatment modalities against HSV1 cause toxicity and drug resistance issues. In the search for alternative forms of treatment, we have uncovered a small molecule, BX795, as a candidate drug with strong antiviral potential owing to its multitargeted mode of action. In this study, we show that in addition to a previously known mechanism of action, BX795 can directly interact with the proviral host factor protein kinase C (PKC) in silico. When administered to HSV1 or mock infected human corneal epithelial (HCE) cells, BX795 significantly reduces the protein level and perinuclear localization of proviral PKC-α and PKC-ζ isoforms. This activity closely mimics that of a known PKC inhibitor, Bisindolylmaleimide I (BIM I), which also inhibits viral replication. Taken together our studies demonstrate a previously unknown mechanism by which BX795 exerts its antiviral potential.

KW - Antiviral

KW - BX795

KW - Herpesvirus

KW - Mechanism

KW - Protein kinase C

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DO - 10.1016/j.antiviral.2022.105454

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AN - SCOPUS:85142773049

SN - 0166-3542

VL - 208

JO - Antiviral Research

JF - Antiviral Research

M1 - 105454

ER -

Putative targeting by BX795 causes decrease in protein kinase C protein levels and inhibition of HSV1 infection

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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