| Autor: |
De S; Institute of Life Sciencesgrid.418782.0, Bhubaneswar, Odisha, India.; Regional Centre for Biotechnology, Faridabad, Haryana, India., Ghosh S; Institute of Life Sciencesgrid.418782.0, Bhubaneswar, Odisha, India.; Regional Centre for Biotechnology, Faridabad, Haryana, India., Keshry SS; Institute of Life Sciencesgrid.418782.0, Bhubaneswar, Odisha, India.; School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT) University, Bhubaneswar, Odisha, India., Mahish C; National Institute of Science Education and Research, Bhubaneswar, Odisha, India.; Homi Bhabha National Institute, Training School Complex, Mumbai, Maharashtra, India., Mohapatra C; Institute of Life Sciencesgrid.418782.0, Bhubaneswar, Odisha, India., Guru A; Institute of Life Sciencesgrid.418782.0, Bhubaneswar, Odisha, India.; Regional Centre for Biotechnology, Faridabad, Haryana, India., Mamidi P; Institute of Life Sciencesgrid.418782.0, Bhubaneswar, Odisha, India., Datey A; Institute of Life Sciencesgrid.418782.0, Bhubaneswar, Odisha, India.; School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT) University, Bhubaneswar, Odisha, India., Pani SS; Institute of Life Sciencesgrid.418782.0, Bhubaneswar, Odisha, India., Vasudevan D; Institute of Life Sciencesgrid.418782.0, Bhubaneswar, Odisha, India., Beuria TK; Institute of Life Sciencesgrid.418782.0, Bhubaneswar, Odisha, India., Chattopadhyay S; National Institute of Science Education and Research, Bhubaneswar, Odisha, India., Subudhi BB; School of Pharmaceutical Sciences, Siksha O Anusandhan Deemed to be University, Bhubaneswar, Odisha, India., Chattopadhyay S; Institute of Life Sciencesgrid.418782.0, Bhubaneswar, Odisha, India. |
| Abstrakt: |
The increase in disease incidences and persistent Chikungunya virus (CHIKV)-induced arthritis have been a huge burden on public health globally. In the absence of specific antivirals or vaccines, it is essential to continue efforts to develop effective anti-CHIKV strategies. Our previous study showing the in vitro anti-CHIKV potential of a novel molecule 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea (MBZM-N-IBT) encouraged us to further validate its efficacy. Here, the effect of MBZM-N-IBT was evaluated in vitro in RAW 264.7 cells, in vivo in C57BL/6 mice, and ex vivo in human peripheral blood mononuclear cells (hPBMCs). The study demonstrated that CHIKV infection was efficiently abrogated in RAW 264.7 cells (IC 50 = 22.34 μM) with significant inhibition in viral proteins. The inhibition was effective in the postentry step, and MBZM-N-IBT predominately interfered in the early stages of CHIKV life cycle. It was further supported when the protease activity of CHIKV-nsP2 was hindered by the compound. Moreover, it diminished the CHIKV-induced inflammatory responses in vitro through significant downregulation of all the major mitogen-activated protein kinases (MAPKs), NF-κB, cyclooxygenase (COX)-2, and cytokines. Furthermore, MBZM-N-IBT restricted CHIKV infection and inflammation in vivo , leading to reduced clinical scores and complete survival of C57BL/6 mice. Additionally, it has been noticed that the CHIKV infection was reduced remarkably in hPBMC-derived monocyte-macrophage populations ex vivo by the compound. In conclusion, it can be suggested that this novel compound MBZM-N-IBT has been demonstrated to be a potential anti-CHIKV molecule in vitro , in vivo , and ex vivo and fulfilled all the criteria to investigate further for successful treatment of CHIKV infection. |
