Sulfamoylbenzamide-based Capsid Assembly Modulators for Selective Inhibition of Hepatitis B Viral Replication

Yeon Hee Lee; Hyeon Min Cha; Jun Yeon Hwang; So Yeong Park; Avinash G. Vishakantegowda; Ali Imran; Joo Youn Lee; Yoon Sun Yi; Sangmi Jun; Ga Hyeon Kim; Hyo Jin Kang; Sang J. Chung; Meehyein Kim; Hyejin Kim; Soo Bong Han

doi:10.1021/acsmedchemlett.0c00606

Sulfamoylbenzamide-based Capsid Assembly Modulators for Selective Inhibition of Hepatitis B Viral Replication

Yeon Hee Lee, Hyeon Min Cha, Jun Yeon Hwang, So Yeong Park, Avinash G. Vishakantegowda, Ali Imran, Joo Youn Lee, Yoon Sun Yi, Sangmi Jun, Ga Hyeon Kim, Hyo Jin Kang, Sang J. Chung, Meehyein Kim, Hyejin Kim, Soo Bong Han

Department of Pharmacy

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

15 Scopus citations

Abstract

As the spread of infections caused by hepatitis B virus (HBV) threatens public health worldwide, investigations from multiple perspectives and of various mechanisms of action are urgently required to increase the HBV cure rate. Targeting the encapsidation of the nuclear capsid protein (core protein, HBc) has emerged as an attractive strategy for inhibiting the viral assembly process; however, a drug targeting this mechanism has not yet been approved. We synthesized novel sulfamoylbenzamides (SBAs) as capsid assembly modulators of HBV and found that the effects and safety profiles of compounds 3 and 8 have potential therapeutic applicability against HBV. The formation of tubular particles was time-dependent in the presence of 3, indicating a new mode of protein assembly by SBA compounds. Our findings provide a new entity for developing safe and efficient treatments for HBV infection.

Original language	English
Pages (from-to)	242-248
Number of pages	7
Journal	ACS Medicinal Chemistry Letters
Volume	12
Issue number	2
DOIs	https://doi.org/10.1021/acsmedchemlett.0c00606
State	Published - 11 Feb 2021

Keywords

antiviral
capsid assembly modulator
chronic hepatitis B infection
Hepatitis B virus
sulfamoylbenzamide

UN SDGs

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

Access to Document

10.1021/acsmedchemlett.0c00606

Cite this

Lee, Y. H., Cha, H. M., Hwang, J. Y., Park, S. Y., Vishakantegowda, A. G., Imran, A., Lee, J. Y., Yi, Y. S., Jun, S., Kim, G. H., Kang, H. J., Chung, S. J., Kim, M., Kim, H., & Han, S. B. (2021). Sulfamoylbenzamide-based Capsid Assembly Modulators for Selective Inhibition of Hepatitis B Viral Replication. ACS Medicinal Chemistry Letters, 12(2), 242-248. https://doi.org/10.1021/acsmedchemlett.0c00606

@article{8ebf0ed9b02b42639957d6bafd6ad978,

title = "Sulfamoylbenzamide-based Capsid Assembly Modulators for Selective Inhibition of Hepatitis B Viral Replication",

abstract = "As the spread of infections caused by hepatitis B virus (HBV) threatens public health worldwide, investigations from multiple perspectives and of various mechanisms of action are urgently required to increase the HBV cure rate. Targeting the encapsidation of the nuclear capsid protein (core protein, HBc) has emerged as an attractive strategy for inhibiting the viral assembly process; however, a drug targeting this mechanism has not yet been approved. We synthesized novel sulfamoylbenzamides (SBAs) as capsid assembly modulators of HBV and found that the effects and safety profiles of compounds 3 and 8 have potential therapeutic applicability against HBV. The formation of tubular particles was time-dependent in the presence of 3, indicating a new mode of protein assembly by SBA compounds. Our findings provide a new entity for developing safe and efficient treatments for HBV infection.",

keywords = "antiviral, capsid assembly modulator, chronic hepatitis B infection, Hepatitis B virus, sulfamoylbenzamide",

author = "Lee, \{Yeon Hee\} and Cha, \{Hyeon Min\} and Hwang, \{Jun Yeon\} and Park, \{So Yeong\} and Vishakantegowda, \{Avinash G.\} and Ali Imran and Lee, \{Joo Youn\} and Yi, \{Yoon Sun\} and Sangmi Jun and Kim, \{Ga Hyeon\} and Kang, \{Hyo Jin\} and Chung, \{Sang J.\} and Meehyein Kim and Hyejin Kim and Han, \{Soo Bong\}",

note = "Publisher Copyright: {\textcopyright} 2021 American Chemical Society.",

year = "2021",

month = feb,

day = "11",

doi = "10.1021/acsmedchemlett.0c00606",

language = "English",

volume = "12",

pages = "242--248",

journal = "ACS Medicinal Chemistry Letters",

issn = "1948-5875",

publisher = "American Chemical Society",

number = "2",

}

Lee, YH, Cha, HM, Hwang, JY, Park, SY, Vishakantegowda, AG, Imran, A, Lee, JY, Yi, YS, Jun, S, Kim, GH, Kang, HJ, Chung, SJ, Kim, M, Kim, H & Han, SB 2021, 'Sulfamoylbenzamide-based Capsid Assembly Modulators for Selective Inhibition of Hepatitis B Viral Replication', ACS Medicinal Chemistry Letters, vol. 12, no. 2, pp. 242-248. https://doi.org/10.1021/acsmedchemlett.0c00606

TY - JOUR

T1 - Sulfamoylbenzamide-based Capsid Assembly Modulators for Selective Inhibition of Hepatitis B Viral Replication

AU - Lee, Yeon Hee

AU - Cha, Hyeon Min

AU - Hwang, Jun Yeon

AU - Park, So Yeong

AU - Vishakantegowda, Avinash G.

AU - Imran, Ali

AU - Lee, Joo Youn

AU - Yi, Yoon Sun

AU - Jun, Sangmi

AU - Kim, Ga Hyeon

AU - Kang, Hyo Jin

AU - Chung, Sang J.

AU - Kim, Meehyein

AU - Kim, Hyejin

AU - Han, Soo Bong

PY - 2021/2/11

Y1 - 2021/2/11

N2 - As the spread of infections caused by hepatitis B virus (HBV) threatens public health worldwide, investigations from multiple perspectives and of various mechanisms of action are urgently required to increase the HBV cure rate. Targeting the encapsidation of the nuclear capsid protein (core protein, HBc) has emerged as an attractive strategy for inhibiting the viral assembly process; however, a drug targeting this mechanism has not yet been approved. We synthesized novel sulfamoylbenzamides (SBAs) as capsid assembly modulators of HBV and found that the effects and safety profiles of compounds 3 and 8 have potential therapeutic applicability against HBV. The formation of tubular particles was time-dependent in the presence of 3, indicating a new mode of protein assembly by SBA compounds. Our findings provide a new entity for developing safe and efficient treatments for HBV infection.

AB - As the spread of infections caused by hepatitis B virus (HBV) threatens public health worldwide, investigations from multiple perspectives and of various mechanisms of action are urgently required to increase the HBV cure rate. Targeting the encapsidation of the nuclear capsid protein (core protein, HBc) has emerged as an attractive strategy for inhibiting the viral assembly process; however, a drug targeting this mechanism has not yet been approved. We synthesized novel sulfamoylbenzamides (SBAs) as capsid assembly modulators of HBV and found that the effects and safety profiles of compounds 3 and 8 have potential therapeutic applicability against HBV. The formation of tubular particles was time-dependent in the presence of 3, indicating a new mode of protein assembly by SBA compounds. Our findings provide a new entity for developing safe and efficient treatments for HBV infection.

KW - antiviral

KW - capsid assembly modulator

KW - chronic hepatitis B infection

KW - Hepatitis B virus

KW - sulfamoylbenzamide

UR - https://www.scopus.com/pages/publications/85101052982

U2 - 10.1021/acsmedchemlett.0c00606

DO - 10.1021/acsmedchemlett.0c00606

M3 - Article

AN - SCOPUS:85101052982

SN - 1948-5875

VL - 12

SP - 242

EP - 248

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 2

ER -

Sulfamoylbenzamide-based Capsid Assembly Modulators for Selective Inhibition of Hepatitis B Viral Replication

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this