Potential Lead from Acacia nilotica (L.) Delile Against Hepatitis C virus - An In silico Approach
By: LEKSHMI, RADHA KESAVAN
.
Contributor(s): CHARUVIL, K. B.
Publisher: Mumbai Indian Journal of Pharmaceutical Science 2021Edition: Vol.83(3), May-June.Description: 443-450p.Subject(s): PHARMACEUTICSOnline resources: Click here
In:
Indian journal of pharmaceutical sciencesSummary: Hepatitis C virus infection is the leading cause of chronic liver disease and hepatocellular carcinoma. There
is no effective vaccine for hepatitis C virus prevention despite the fact that several vaccines are under
development. Currently, the Unites States Food and drug administration approved combination drugs for
all genotypes that would help to cure the infection more quickly and efficiently than ever before. However,
the high costs, development of various side effects and emergence of drug resistant strains demand the
need for new anti-viral to treat different stages of the hepatitis C virus life cycle. Focussing drug candidate
from herbal ingredients is the novel approach of pharmaceutical science over the past few decades. In this
perspective, the present study aimed to investigate the phytochemicals present inAcacia nilotica (L.) Delile
against hepatitis C virus non-structural protein3-4A serine protease. The N-terminal Protease domain
of non-structural protein3 along with non-structural protein4A protein is responsible for the cleavage
of four polypeptide junctions’ viz., non-structural protein3-4A, non-structural protein4A-non-structural
protein4B, non-structural protein4B-non-structural protein5A and non-structural protein5A-5B that are
essential for viral genome replication. Hence targeting non-structural protein3-4A blocks the replication
process. Here, in silico molecular docking study was executed to estimate the efficacy of phytochemicals
along with the two Food and drug administration approved hepatitis C virus non-structural protein3-
4A inhibitors-Grazoprevir and simeprevir as reference compounds against the selected target. Docking
results revealed that about six phytochemicals (+)-Catechin 5-Gallate, Acacetin, (+)-Mollisacacidin,
Catechin, Acalinol A and Chlorogenic acid are better than the reference compounds and hence selected as
hits. Further, the hit molecules were filtered through analysing druglikeness properties, pharmacokinetics,
medicinal chemistry friendliness including pan assay interference compounds and Brenk structural alerts,
leadlikeness and finally prediction of potential toxicity and toxic substructure to ascertain a lead molecule.
The results obtained in the current study propose Acacetin as the lead molecule for further in vitro and
in vivo study.
| Item type | Current location | Call number | Status | Date due | Barcode | Item holds |
|---|---|---|---|---|---|---|
Articles Abstract Database
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School of Pharmacy Archieval Section | Not for loan | 2021-2022552 |
Hepatitis C virus infection is the leading cause of chronic liver disease and hepatocellular carcinoma. There
is no effective vaccine for hepatitis C virus prevention despite the fact that several vaccines are under
development. Currently, the Unites States Food and drug administration approved combination drugs for
all genotypes that would help to cure the infection more quickly and efficiently than ever before. However,
the high costs, development of various side effects and emergence of drug resistant strains demand the
need for new anti-viral to treat different stages of the hepatitis C virus life cycle. Focussing drug candidate
from herbal ingredients is the novel approach of pharmaceutical science over the past few decades. In this
perspective, the present study aimed to investigate the phytochemicals present inAcacia nilotica (L.) Delile
against hepatitis C virus non-structural protein3-4A serine protease. The N-terminal Protease domain
of non-structural protein3 along with non-structural protein4A protein is responsible for the cleavage
of four polypeptide junctions’ viz., non-structural protein3-4A, non-structural protein4A-non-structural
protein4B, non-structural protein4B-non-structural protein5A and non-structural protein5A-5B that are
essential for viral genome replication. Hence targeting non-structural protein3-4A blocks the replication
process. Here, in silico molecular docking study was executed to estimate the efficacy of phytochemicals
along with the two Food and drug administration approved hepatitis C virus non-structural protein3-
4A inhibitors-Grazoprevir and simeprevir as reference compounds against the selected target. Docking
results revealed that about six phytochemicals (+)-Catechin 5-Gallate, Acacetin, (+)-Mollisacacidin,
Catechin, Acalinol A and Chlorogenic acid are better than the reference compounds and hence selected as
hits. Further, the hit molecules were filtered through analysing druglikeness properties, pharmacokinetics,
medicinal chemistry friendliness including pan assay interference compounds and Brenk structural alerts,
leadlikeness and finally prediction of potential toxicity and toxic substructure to ascertain a lead molecule.
The results obtained in the current study propose Acacetin as the lead molecule for further in vitro and
in vivo study.
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