Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2

Ly Hien Doan, Li Wei Chu, Zi Yi Huang, Anh Thuc Nguyen, Chia Yin Lee, Chien Ling Huang, Yu Fen Chang, Wen Yu Hsieh, Trang Thi Huyen Nguyen, Chao Hsiung Lin, Chun Li Su, Tsung Hsien Chuang, Jin Mei Lai, Feng Sheng Wang, Chia Jui Yang, Hui Kang Liu*, Yueh Hsin Ping*, Chi Ying F. Huang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Coronavirus disease 2019 (COVID-19) remains a threat with the emergence of new variants, especially Delta and Omicron, without specific effective therapeutic drugs. The infection causes dysregulation of the immune system with a cytokine storm that eventually leads to fatal acute respiratory distress syndrome (ARDS) and further irreversible pulmonary fibrosis. Therefore, the promising way to inhibit infection is to disrupt the binding and fusion between the viral spike and the host ACE2 receptor. A transcriptome-based drug screening platform has been developed for COVID-19 to explore the possibility and potential of the long-established drugs or herbal medicines to reverse the unique genetic signature of COVID-19. In silico analysis showed that Virofree, an herbal medicine, reversed the genetic signature of COVID-19 and ARDS. Biochemical validations showed that Virofree could disrupt the binding of wild-type and Delta-variant spike proteins to ACE2 and its syncytial formation via cell-based pseudo-typed viral assays, as well as suppress binding between several variant recombinant spikes to ACE2, especially Delta and Omicron. Additionally, Virofree elevated miR-148b-5p levels, inhibited the main protease of SARS-CoV-2 (Mpro), and reduced LPS-induced TNF-α release. Virofree also prevented cellular iron accumulation leading to ferroptosis which occurs in SARS-CoV-2 patients. Furthermore, Virofree was able to reduce pulmonary fibrosis-related protein expression levels in vitro. In conclusion, Virofree was repurposed as a potential herbal medicine to combat COVID-19. This study highlights the inhibitory effect of Virofree on the entry of Delta and Omicron variants of SARS-CoV-2, which have not had any effective treatments during the emergence of the new variants spreading.

Original languageEnglish
Article number905197
JournalFrontiers in Pharmacology
Publication statusPublished - 2022 Jul 4


  • ACE2 (angiotensin-converting enzyme 2)
  • COVID-19
  • Delta variant (B.1.617.2)
  • Omicron variant (SARS-CoV-2)
  • SARS-CoV-2 variants
  • herbal medicine
  • miRNA

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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