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.
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright of this article belongs to Elsevier Science. |
| Uncontrolled Keywords: | Chikungunya nsP2Virtual drug screeningBiophysical validationSAXSAntiviral assay |
| Subjects: | Q Science > QR Microbiology > QR355 Virology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 24 Sep 2020 08:51 |
| Last Modified: | 24 Sep 2020 08:51 |
| URI: | http://crdd.osdd.net/open/id/eprint/2603 |
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