TY - JOUR
T1 - The Life Cycle and in silico Elucidation of Non-structural Replicating Proteins of HCV Through a Pharmacoinformatics Approach
AU - Tahir, Rana Adnan
AU - Mughal, Sumera
AU - Nazir, Amina
AU - Noureen, Asma
AU - Jawad, Ayesha
AU - Waqas, Muhammad
AU - Sehgal, Sheikh Arslan
N1 - Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
PY - 2022
Y1 - 2022
N2 - BACKGROUND: Hepatitis C virus (HCV) is an enveloped and positive-stranded RNA virus that is a major causative agent of chronic liver diseases worldwide. HCV has become the main cause of liver transplantations and there is no effective drug for all hepatitis genotypes. Elucidation of the life cycle and non-structural proteins of HCV, involved in viral replication, are attractive targets for the development of antiviral drugs..METHODS: In this work, pharmacoinformatics approaches coupled with docking analyses were applied on HCV non-structural proteins to identify the novel potential hits and HCV drugs. Molecular docking analyses were carried out on HCV-approved drugs, followed by the ligandbased pharmacophore generation to screen the antiviral libraries for novel potential hits.RESULTS: Virtual screening technique has top-ranked five novel compounds (ZINC00607900, ZINC03635748, ZINC03875543, ZINC04097464, and ZINC12503102) along with their least binding energies (-8.0 kcal/mol, -6.1 kcal/mol, -7.5 kcal/mol, -7.4 kcal/mol, and -7.3 kcal/mol, respectively) and stability with the non-structural proteins target.CONCLUSION: These promising hits exhibited better absorption and ADMET properties as compared to the selected drug molecules. These potential compounds extracted from in silico approach may be significant in drug design and development against Hepatitis and other liver diseases.
AB - BACKGROUND: Hepatitis C virus (HCV) is an enveloped and positive-stranded RNA virus that is a major causative agent of chronic liver diseases worldwide. HCV has become the main cause of liver transplantations and there is no effective drug for all hepatitis genotypes. Elucidation of the life cycle and non-structural proteins of HCV, involved in viral replication, are attractive targets for the development of antiviral drugs..METHODS: In this work, pharmacoinformatics approaches coupled with docking analyses were applied on HCV non-structural proteins to identify the novel potential hits and HCV drugs. Molecular docking analyses were carried out on HCV-approved drugs, followed by the ligandbased pharmacophore generation to screen the antiviral libraries for novel potential hits.RESULTS: Virtual screening technique has top-ranked five novel compounds (ZINC00607900, ZINC03635748, ZINC03875543, ZINC04097464, and ZINC12503102) along with their least binding energies (-8.0 kcal/mol, -6.1 kcal/mol, -7.5 kcal/mol, -7.4 kcal/mol, and -7.3 kcal/mol, respectively) and stability with the non-structural proteins target.CONCLUSION: These promising hits exhibited better absorption and ADMET properties as compared to the selected drug molecules. These potential compounds extracted from in silico approach may be significant in drug design and development against Hepatitis and other liver diseases.
KW - Animals
KW - Antiviral Agents/chemistry
KW - Hepacivirus
KW - Hepatitis C/drug therapy
KW - Ligands
KW - Molecular Docking Simulation
KW - Viral Nonstructural Proteins/chemistry
UR - http://www.scopus.com/inward/record.url?scp=85123650257&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123650257&partnerID=8YFLogxK
U2 - 10.2174/1386207324666210217144306
DO - 10.2174/1386207324666210217144306
M3 - Article
C2 - 33596796
SN - 1386-2073
VL - 25
SP - 689
EP - 701
JO - Combinatorial Chemistry and High Throughput Screening
JF - Combinatorial Chemistry and High Throughput Screening
IS - 4
ER -