Human herpesviruses are known to induce a broad spectrum of diseases, ranging from common cold sores to cancer, and infections with some types of these viruses, known as human oncogenic herpesviruses (HOHVs), can cause cancer. Challenges with viral latency, recurrent infections, and drug resistance have generated the need for finding new drugs with the ability to overcome these barriers. Berberine (BBR), a naturally occurring alkaloid, is known for its multiple biological activities, including antiviral and anticancer effects. This paper comprehensively compiles all studies that have featured anti-HOHV properties of BBR along with promising preventive effects against the associated cancers. The mechanisms and pathways induced by BBR via targeting the herpesvirus life cycle and the pathogenesis of the linked malignancies are reviewed. Approaches to enhance the therapeutic efficacy of BBR and its use in clinical practice as an anti-herpesvirus drug are also discussed.

• Keywords
• Epstein–Barr virus, Kaposi’s sarcoma-associated herpesvirus, berberine, cancer, herpes simplex virus, human cytomegalovirus, inflammation, oncogenic herpesviruses,
• MeSH
• Antiviral Agents therapeutic use   MeSH
• Berberine therapeutic use   MeSH
• Herpesviridae classification   drug effects   pathogenicity   MeSH
• Herpesviridae Infections complications   drug therapy   MeSH
• Carcinogenesis drug effects   MeSH
• Clinical Trials as Topic MeSH
• Virus Latency drug effects   MeSH
• Humans MeSH
• Mice MeSH
• Neoplasms drug therapy   virology   MeSH
• Virus Replication drug effects   MeSH
• Inflammation drug therapy   virology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Antiviral Agents MeSH
• Berberine MeSH

This study explored the antitubercular properties of fucoxanthin, a marine carotenoid, against clinical isolates of Mycobacterium tuberculosis (Mtb). Two vital enzymes involved in Mtb cell wall biosynthesis, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), were selected as drug targets to reveal the mechanism underlying the antitubercular effect of fucoxanthin. The obtained results showed that fucoxanthin showed a clear bacteriostatic action against the all Mtb strains tested, with minimum inhibitory concentrations (MIC) ranging from 2.8 to 4.1 µM, along with a good degree of selectivity index (ranging from 6.1 to 8.9) based on cellular toxicity evaluation compared with standard drug isoniazid (INH). The potent inhibitory actions of fucoxanthin and standard uridine-5'-diphosphate against UGM were recorded to be 98.2% and 99.2%, respectively. TBNAT was potently inactivated by fucoxanthin (half maximal inhibitory concentration (IC50) = 4.8 µM; 99.1% inhibition) as compared to INH (IC50 = 5.9 µM; 97.4% inhibition). Further, molecular docking approaches were achieved to endorse and rationalize the biological findings along with envisaging structure-activity relationships. Since the clinical evidence of the last decade has confirmed the correlation between bacterial infections and autoimmune diseases, in this study we have discussed the linkage between infection with Mtb and autoimmune diseases based on previous clinical observations and animal studies. In conclusion, we propose that fucoxanthin could demonstrate great therapeutic value for the treatment of tuberculosis by acting on multiple targets through a bacteriostatic effect as well as by inhibiting UGM and TBNAT. Such outcomes may lead to avoiding or decreasing the susceptibility to autoimmune diseases associated with Mtb infection in a genetically susceptible host.

• Keywords
• Mycobacterium tuberculosis, UDP-galactopyranose mutase, arylamine-N-acetyltransferase, autoimmunity, fucoxanthin, marine carotenoid, pathogenesis,
• MeSH
• Antitubercular Agents pharmacology   MeSH
• Arylamine N-Acetyltransferase metabolism   MeSH
• Autoimmune Diseases drug therapy   MeSH
• Cell Wall drug effects   enzymology   MeSH
• Cell Line MeSH
• Intramolecular Transferases metabolism   MeSH
• Isoenzymes metabolism   MeSH
• Carotenoids pharmacology   MeSH
• Humans MeSH
• Microbial Sensitivity Tests methods   MeSH
• Mycobacterium tuberculosis drug effects   enzymology   MeSH
• Molecular Docking Simulation methods   MeSH
• Tuberculosis drug therapy   MeSH
• Xanthophylls pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antitubercular Agents MeSH
• Arylamine N-Acetyltransferase MeSH
• fucoxanthin MeSH Browser
• Intramolecular Transferases MeSH
• Isoenzymes MeSH
• Carotenoids MeSH
• N-acetyltransferase 1 MeSH Browser
• UDP-galactopyranose mutase MeSH Browser
• Xanthophylls MeSH