Structure-Guided Approach to Identify Potential Inhibitors of Large Envelope Protein to Prevent Hepatitis B Virus Infection

Autor: Rafat Ali, Ayesha Anwer, Romana Ishrat, Saniya Khan, Anam Farooqui, Iqbal Azmi, Shahnawaz Ali, Zarrin Minuchehr, Aftab Alam, Mohammad Sabery Anvar, Ruchika Bhat, Mahboubeh Mehmankhah, Md. Imtaiyaz Hassan, Syed Naqui Kazim, Fatima Amir
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Oxidative Medicine and Cellular Longevity, Vol 2019 (2019)
BASE-Bielefeld Academic Search Engine
Oxidative Medicine and Cellular Longevity
ISSN: 1942-0900
1188-2026
DOI: 10.1155/2019/1297484
Popis: Hepatitis B virus (HBV) infection is one of the major causes of liver diseases, which can lead to hepatocellular carcinoma. The role of HBV envelope proteins is crucial in viral morphogenesis, infection, and propagation. Thus, blocking the pleiotropic functions of these proteins especially the PreS1 and PreS2 domains of the large surface protein (LHBs) is a promising strategy for designing efficient antivirals against HBV infection. Unfortunately, the structure of the LHBs protein has not been elucidated yet, and it seems that any structure-based drug discovery is critically dependent on this. To find effective inhibitors of LHBs, we have modeled and validated its three-dimensional structure and subsequently performed a virtual high-throughput screening against the ZINC database using RASPD and ParDOCK tools. We have identified four compounds, ZINC11882026, ZINC19741044, ZINC00653293, and ZINC15000762, showing appreciable binding affinity with the LHBs protein. The drug likeness was further validated using ADME screening and toxicity analysis. Interestingly, three of the four compounds showed the formation of hydrogen bonds with amino acid residues lying in the capsid binding region of the PreS1 domain of LHBs, suggesting the possibility of inhibiting the viral assembly and maturation process. The identification of potential lead molecules will help to discover more potent inhibitors with significant antiviral activities.
Databáze: OpenAIRE
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