The mechanism and pharmacodynamics of 2-((1H-indol-3-yl)thio/sulfinyl)-N-pheny acetamide derivative as a novel inhibitor against human respiratory syncytial virus

Abstract

Human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection worldwide. Until now, there are no licenced vaccines or effective antiviral drugs against RSV infections. In our previous work, we found 2-((1H-indol-3-yl)thio/sulfinyl)-N-pheny acetamide derivatives (4-49 C and 1-HB-63) being a novel inhibitor against RSV in vitro. Here, we explored the underlying mechanism of 2-((1H-indol-3-yl)thio/sulfinyl)-N-pheny acetamide derivatives to inhibit RSV replication in vitro and disclosed that 4–49 C worked as the inhibitor of membrane fusion and 1-HB-63 functioned at the stage of RSV genome replication/transcription. Yet, both of them could not inhibit RSV infection of BALB/c mice by using RSV-Luc, in vivo imaging and RT-qPCR analyses, for which it may be due to the fast metabolism in vivo. Our work suggests that further structural modification and optimisation of 2-((1H-indol-3-yl) thio/sulfinyl)-N-pheny acetamide derivative are needed to obtain drug candidates with effective anti-RSV activities in vivo.

Graphical Abstract

Keywords:

• 2-((1H-indol-3-yl)thio/ sulfinyl)-N-pheny acetamide derivative
• respiratory syncytial virus
• antiviral mechanism
• pharmacodynamics
• in vivo imaging

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors acknowledge the financial support from National Major Scientific and Technological Special Project for “AIDS and Viral Hepatitis and Other Major Infectious Diseases Prevention and Control” during the Twelfth Five-year Plan Period [Grants 2013ZX10004601], the Natural Science Foundation of China [81771777], the National Mega-Project for Infectious Disease [2018ZX10301408] and CAMS Innovation Fund for Medical Sciences [2018-I2M-3-004].