Recent Advances in the Development of Sulfamoyl-Based Hepatitis B Virus Nucleocapsid Assembly Modulators

Recent Advances in the Development of Sulfamoyl-Based Hepatitis B Virus Nucleocapsid Assembly Modulators

Hepatitis B virus (HBV) is the primary contributor to severe liver ailments, encompassing conditions such as cirrhosis and hepatocellular carcinoma. Globally, 257 million people are affected by HBV annually and 887,000 deaths are attributed to it, representing a substantial health burden. Regrettabl...

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Bibliographic Details
Published in:Viruses Vol. 15; no. 12; p. 2367
Main Authors: Nayak, Sandesha, Gowda, Jayaraj, Abbas, Syed Azeem, Kim, Hyejin, Han, Soo Bong
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 30-11-2023
Subjects:
Antigens
Antiviral agents
Antiviral Agents - therapeutic use
CAMs
Capsid - metabolism
Capsid Proteins - genetics
cccDNA
Circular DNA
Cirrhosis
Core protein
DNA methylation
DNA, Circular - genetics
DNA, Circular - metabolism
DNA, Viral - genetics
DNA, Viral - metabolism
Dosage and administration
Drug therapy
Genomes
HBV core protein
Health aspects
Heparan sulfate
Hepatitis B
Hepatitis B - drug therapy
Hepatitis B - metabolism
Hepatitis B virus
Hepatitis B virus - metabolism
Hepatitis B, Chronic - drug therapy
Hepatocellular carcinoma
Hepatocytes
Humans
Infections
Kinases
Medical research
Medicine, Experimental
Nucleocapsid - metabolism
Nucleocapsids
Replication
Sulfonamides
Virus Replication
South Korea
HBV core protein
CAMs
cccDNA
hepatitis B virus
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Summary:Hepatitis B virus (HBV) is the primary contributor to severe liver ailments, encompassing conditions such as cirrhosis and hepatocellular carcinoma. Globally, 257 million people are affected by HBV annually and 887,000 deaths are attributed to it, representing a substantial health burden. Regrettably, none of the existing therapies for chronic hepatitis B (CHB) have achieved satisfactory clinical cure rates. This issue stems from the existence of covalently closed circular DNA (cccDNA), which is difficult to eliminate from the nucleus of infected hepatocytes. HBV genetic material is composed of partially double-stranded DNA that forms complexes with viral polymerase inside an icosahedral capsid composed of a dimeric core protein. The HBV core protein, consisting of 183 to 185 amino acids, plays integral roles in multiple essential functions within the HBV replication process. In this review, we describe the effects of sulfamoyl-based carboxamide capsid assembly modulators (CAMs) on capsid assembly, which can suppress HBV replication and disrupt the production of new cccDNA. We present research on classical, first-generation sulfamoyl benzocarboxamide CAMs, elucidating their structural composition and antiviral efficacy. Additionally, we explore newly identified sulfamoyl-based CAMs, including sulfamoyl bicyclic carboxamides, sulfamoyl aromatic heterocyclic carboxamides, sulfamoyl aliphatic heterocyclic carboxamides, cyclic sulfonamides, and non-carboxamide sulfomoyl-based CAMs. We believe that certain molecules derived from sulfamoyl groups have the potential to be developed into essential components of a well-suited combination therapy, ultimately yielding superior clinical efficacy outcomes in the future.
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ISSN:1999-4915
1999-4915
DOI:10.3390/v15122367