title: Inhibition of Chikungunya Virus Replication by 1-[(2-Methylbenzimidazol-1-yl) Methyl]-2-Oxo-Indolin-3-ylidene] Amino] Thiourea(MBZM-N-IBT).
abstract: Chikungunya virus (CHIKV) infection is one of the most challenging human Arboviral infections with global significance and without any specific antiviral. In this investigation, 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea (MBZM-N-IBT) was synthesised as a molecular hybrid of 2-methyl benzimidazole and isatin-β-thiosemicarbazone and its anti-CHIKV property was evaluated. The release of infectious virus particles was calculated by plaque assay, expression profile of viral RNA was estimated by RT-PCR and viral protein profiles were assessed by Western blot and FACS analyses. The safety index of MBZM-N-IBT was found to be >21. The CHIKV infectious viral particle formation was abrogated around 76.02% by MBZM-N-IBT during infection in mammalian system and the viral RNA synthesis was reduced by 65.53% and 23.71% for nsP2 and E1 respectively. Surprisingly, the viral protein levels were reduced by 97% for both nsP2 and E2. In the time-of-addition experiment it abrogated viral infection at early as well as late phase of viral life cycle, which indicates about multiple mechanisms for its anti-CHIKV action. In silico analysis justified development of MBZM-N-IBT with good affinities for potential target proteins of CHIKV and related virus. With predictions of good drug-likeness property, it shows potential of a drug candidate which needs further experimental validation.
authors: School of Pharmaceutical Sciences, Siksha O Anusandhan University, Bhubaneswar, India.
authors: Priyadarsee
authors: P
authors: Mishra
authors: Institute of Life Sciences, Bhubaneswar, India.
authors: Abhishek
authors: A
authors: Kumar
authors: Institute of Life Sciences, Bhubaneswar, India.
authors: Prabhudutta
authors: P
authors: Mamidi
authors: Institute of Life Sciences, Bhubaneswar, India.
authors: Sameer
authors: S
authors: Kumar
authors: Institute of Life Sciences, Bhubaneswar, India.
authors: Itishree
authors: I
authors: Basantray
authors: Institute of Life Sciences, Bhubaneswar, India.
authors: Tanuja
authors: T
authors: Saswat
authors: Institute of Life Sciences, Bhubaneswar, India.
authors: Indrani
authors: I
authors: Das
authors: School of Biological Sciences, National Institute of Science Education &Research, Bhubaneswar, India.
authors: Tapas Kumar
authors: TK
authors: Nayak
authors: School of Biological Sciences, National Institute of Science Education &Research, Bhubaneswar, India.
authors: Subhasis
authors: S
authors: Chattopadhyay
authors: School of Pharmaceutical Sciences, Siksha O Anusandhan University, Bhubaneswar, India.
authors: Bharat Bhusan
authors: BB
authors: Subudhi
authors: Institute of Life Sciences, Bhubaneswar, India.
authors: Soma
authors: S
authors: Chattopadhyay
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002646:Chikungunya virus / Q000502:physiology*; D002522:Chlorocebus aethiops; D005434:Flow Cytometry; D007510:Isatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013890:Thiourea / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C000613466:1-((2-methylbenzimidazol-1-yl)methyl)-2-oxoindolin-3-ylidene)amino)thiourea; D000998:Antiviral Agents; D001562:Benzimidazoles; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D007510:Isatin; D013890:Thiourea