With the devastating impact of the COVID-19 on populations all over the world, there is an urgent need to find effective vaccines and treatments that can target this virus. SARS-CoV-2 had infected more than 209 million people, with nearly 4.4 million deaths.

Despite the global rollout of many vaccines, there is still a scarcity of inexpensive anti-SARS-CoV-2 drugs. Antiviral therapy research has been very beneficial in treating patients with severe COVID-19 symptoms. Furthermore, the advent of novel SARS-CoV-2 variants of concern (VOCs) has raised the need for effective therapies to be developed and administered.

In a recent study, the researchers created a high-content screen (HCS) using Apteeus (TEELibrary®), a drug library that had a complete collection of 1,942 authorised drugs. The HCS approach was used to screen and identify compounds with SARS-CoV-2 antiviral activity.

Only three of the initial compounds tested in this investigation were shown to have a dose-dependent antiviral activity against SARS-CoV-2 in Vero-81 cells, both in the presence and absence of TMPRSS2. These compounds included perphenazine, nitazoxaine, and clofoctol, the latter of which was chosen for further research because of its anti-SARS-CoV-2 characteristics.

Clofoctol is an antibacterial medicine that was first created in the 1970s and has been demonstrated to be successful in the treatment of Streptococcus pneumoniae, the major global cause of bacterial pneumonia, and Staphylococcus aureus. Clofoctol inhibits bacterial cell wall production while increasing membrane permeability. It has also been shown to impede protein translation and slow tumour growth.

The findings also revealed that clofoctol can suppress SARS-CoV-2 by preventing the translation of viral ribonucleic acid (RNA), which is essential for the virus’s propagation. This could be due to the activation of the unfolded protein response (UPR) pathways, as this pharmacological molecule has been reported to produce endoplasmic reticulum stress and activate all three UPR pathways. Among these pathways are inositol requiring enzyme 1 (IRE1), double-stranded RNA-activated PK-like ER kinase (PERK), and activating transcription factor 6. (ATF6).

Interference with these UPR pathways has been shown to prevent viruses such as SARS-CoV-2 from replicating.

The researchers revealed that clofoctol has antiviral activity against SARS-CoV-2 in vitro in this investigation. Additionally, this study’s in vivo data revealed that clofoctol dramatically decreased the viral load of SARS-CoV-2 in the lungs of transgenic C57BL-6 mice expressing the human angiotensin-converting enzyme 2 (ACE2) receptor, as well as pulmonary inflammation.

Taken together, the findings of this study lead the researchers to endorse clofoctol as a viable therapeutic option for SARS-CoV-2 infection. A phase 2/3 placebo-controlled trial is currently being prepared to further confirm this drug’s anti-COVID-19 activity.

The results of the study were published in the journal bioRxiv.