Salicylic Acid Conjugate of Telmisartan Inhibits Chikungunya Virus Infection and Inflammation

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2024 Jan 15

PMID 38222605

Authors

Rudra Narayan Dash

Amrita Ray

Prabhudutta Mamidi

Saikat De

Tapas K Mohapatra

Alok K Moharana

Tathagata Mukherjee

Soumyajit Ghosh

Subhasis Chattopadhyay

Bharat B Subudhi

Soma Chattopadhyay

Affiliations

Soon will be listed here.

Abstract

There is no approved antiviral for the management of the Chikungunya virus (CHIKV). To develop an antiviral drug that can manage both CHIKV and arthritis induced by it, an ester conjugate of telmisartan (TM) and salicylic acid (SA) was synthesized (DDABT1). It showed higher potency (IC of 14.53 μM) and a good selectivity index [(SI = CC/IC) > 33]. On post-treatment of DDABT1, CHIKV infection was inhibited significantly by reducing CPE, viral titer, viral RNA, and viral proteins. Further, the time of addition experiment revealed >95% inhibition up to 4hpi indicating its interference predominantly in the early stages of infection. However, the late stages were also affected. This conjugate of SA and TM was found to increase the antiviral efficacy, and this might be partly attributed to modulating angiotensin II (Ang II) receptor type 1 (AT1). However, DDABT1 might have other modes of action that need further investigation. In addition, the in vivo experiments showed an LD of 5000 mg/kg in rats and was found to be more effective than TM, SA, or their combination against acute, subacute, and chronic inflammation/arthritis . In conclusion, DDABT1 showed remarkable anti-CHIKV properties and the ability to reduce inflammation and arthritis, making it a very good potential drug candidate that needs further experimental validation.

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