# N-alkyl and N-benzyl indoles are anti-SARS-CoV-2 agents and nsp13 inhibitors

## TL;DR

This study identifies N-benzyl indoles as potential antiviral agents against SARS-CoV-2 by inhibiting the nsp13 protein, which is crucial for viral replication.

## Contribution

The paper introduces novel N-benzyl indole derivatives as effective SARS-CoV-2 nsp13 inhibitors with antiviral activity and low cytotoxicity.

## Key findings

- N-benzyl indole derivatives inhibited SARS-CoV-2 nsp13 enzymatic activities with IC50 values under 30 μM.
- The compounds blocked viral replication without causing cytotoxicity.
- Docking studies suggest binding to an allosteric site in the RecA2 domain of nsp13.

## Abstract

COVID-19 pandemic stimulated tremendous efforts to develop therapeutic strategies targeting SARS-CoV-2, leading to the evaluation of a wide range of potential treatments in clinical trials. However, effective therapeutics remain elusive when the development of new variants and the limits of antiviral drugs is considered. Therefore, the development of antiviral drugs against SARS-CoV-2 is of paramount importance. Among potential drug targets, the SARS-CoV-2 nsp13 is highly attractive thanks to its pivotal role in viral replication. Pursuing our studies on the development of nsp13 inhibitors, in this work we describe the design, synthesis, and biological evaluation of novel inhibitors targeting SARS-CoV-2 nsp13. The newly designed N-benzyl indole derivatives were active against both enzymatic activities showing measurable IC50 under 30 μM concentration, while N-alkyl derivatives showed less promising results. Interestingly, the tested compounds blocked viral replication with no cytotoxicity. Docking studies predicted their binding into an allosteric conserved site located in the RecA2 domain.