Overview

Signal Transduction and Targeted Therapy has recently published a review article that reported the current expertise in the molecular communication of SARS-CoV-2.

There is one session in the article specifically talking about small-molecule compound-based antiviral properties, including small molecules targeting S protein of SARS-CoV-2, TMPRSS2 inhibitors, and cathepsin B/L inhibitors.

Below are some highlights from the article:

Small molecules targeting S protein

  • S protein of SARS-CoV-2 plays an important role in receptor recognition and virus-cell membrane fusion
  • Hydrophilic compound, Salvianolic acid isolated from traditional Chinese medicine, inhibited SAR-CoV-2 infection by blocking the formation of 6-helix bundle core in authentic SARS-CoV-2 inhibition assays
  • 2 drug-like compounds, DRI-C23041 and DRI-C91005, showed antiviral activity in obstructing the interaction between human angiotensin-converting enzyme 2 (hACE2) and SARS-CoV-2 S protein
  • DRI-C23041 inhibited the entry of SARS-CoV-2-S pseudo viral into ACE2-expressing cells

TMPRSS2 inhibitors

  • TMPRSS2 could be used as a potential target to avoid virus entry
  • Camostat mesylate, a TMPRSS2 inhibitor, significantly inhibited SARS-CoV-2 pseudo viral entry into Calu-3 cells
  • MI-432 and MI-1900, two prospective peptide mimetic inhibitors of TMPRSS2, demonstrated antiviral activity against SARS-CoV-2 infection in vitro

Cathepsin B/L inhibitors

  • Cellular cathepsins can prime viral S protein cleavage and benefit viral fusion, including cathepsin B and cathepsin L
  • P9, derived from mouse β-defensin-4, has broad-spectrum antiviral activity against multiple respiratory viruses by interfering with cathepsin L
  • E64-d, a broad cathepsin B/L inhibitor, showed inhibitory activity in a SARS-CoV-2 pseudovirus infection assay

Reference:

Zhang Q, Xiang R, Huo S, Zhou Y, Jiang S, Wang Q, Yu F. Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy. Signal Transduct Target Ther. 2021 Jun 11;6(1):233. doi: 10.1038/s41392-021-00653-w. PMID: 34117216; PMCID: PMC8193598.

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