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Evaluation of novobiocin and telmisartan for anti-CHIKV activity

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Evaluation of novobiocin and telmisartan for anti-CHIKV activity
 
Creator Tripathi, Praveen Kumar
Soni, Anjali
Yadav, Shiv Pratap Singh
Kumar, Ankit
Raghavender, Siva
Sharma, Pradeep
Sujhatha, Sunil
Ashish, .
Jayaram, Bhyravabhotla
Patel, Ashok Kumar
 
Subject QR355 Virology
 
Description Chikungunya has re-emerged as an epidemic with global distribution and high morbidity, necessitating the need for effective therapeutics. We utilized already approved drugs with a good safety profile used in other diseases for their new property of anti-chikungunya activity. It provides a base for a fast and efficient approach to bring a novel therapy from bench to bedside by the process of drug-repositioning. We utilized an in-silico drug screening with FDA approved molecule library to identify inhibitors of the chikungunya nsP2 protease, a multifunctional and essential non-structural protein required for virus replication. Telmisartan, an anti-hypertension drug, and the antibiotic novobiocin emerged among top hits on the screen. Further, SPR experiments revealed strong in-vitro binding of telmisartan and novobiocin to nsP2 protein. Additionally, small angle x-ray scattering suggested binding of molecules to nsP2 and post-binding compaction and retention of monomeric state in the protein-inhibitor complex. Protease activity measurement revealed that both compounds inhibited nsP2 protease activity with IC50 values in the low micromolar range. More importantly, plaque formation assays could show the effectiveness of these drugs in suppressing virus propagation in host cells. We propose novobiocin and telmisartan as potential inhibitors of chikungunya replication. Further research is required to establish the molecules as antivirals of clinical relevance against chikungunya.
 
Publisher Elsevier Science
 
Date 2020-09-15
 
Type Article
PeerReviewed
 
Relation https://www.sciencedirect.com/science/article/abs/pii/S0042682220300970
http://crdd.osdd.net/open/2603/
 
Identifier Tripathi, Praveen Kumar and Soni, Anjali and Yadav, Shiv Pratap Singh and Kumar, Ankit and Raghavender, Siva and Sharma, Pradeep and Sujhatha, Sunil and Ashish, . and Jayaram, Bhyravabhotla and Patel, Ashok Kumar (2020) Evaluation of novobiocin and telmisartan for anti-CHIKV activity. Virology, 548. pp. 250-260.