Development and evaluation of a novel chromium III-based compound for potential inhibition of emerging SARS-CoV-2 variants

Yu-Jung Lin; Navaneethan Sundhar; Hema Sri Devi; Hsueh-Fa Pien; Shina Fong-Mei Wen; Jenn-Line Sheu; Bruce Chi-Kang Tsai; Chih-Yang Huang

doi:10.1016/j.heliyon.2023.e20011

Development and evaluation of a novel chromium III-based compound for potential inhibition of emerging SARS-CoV-2 variants

Heliyon. 2023 Sep 9;9(9):e20011. doi: 10.1016/j.heliyon.2023.e20011. eCollection 2023 Sep.

Authors

Yu-Jung Lin^{1

2}, Navaneethan Sundhar^{1

3}, Hema Sri Devi¹, Hsueh-Fa Pien⁴, Shina Fong-Mei Wen⁴, Jenn-Line Sheu⁴, Bruce Chi-Kang Tsai¹, Chih-Yang Huang^{1

3

5

6

7}

Affiliations

¹ Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
² School of Post-Baccalaureate Chinese Medicine, College of Medicine, Tzu Chi University, Hualien, Taiwan.
³ Graduate Institute of Biomedical Sciences, School of Medicine, China Medical University, Taichung, Taiwan.
⁴ TOMA Biotechnology CO., LTD, Taipei, Taiwan.
⁵ Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
⁶ Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan.
⁷ Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused 403 million cases of coronavirus disease (COVID-19) and resulted in more than 5.7 million deaths worldwide. Extensive research has identified several potential drug treatments for COVID-19. However, the development of new compounds or therapies is necessary to prevent the emergence of drug resistance in SARS-CoV-2. In this study, a novel compound based on hexaacetotetraaquadihydroxochromium(III)diiron(III) nitrate, which contains small amounts of chromium (III), was synthesised and evaluated for its effectiveness against multiple variants of COVID-19 using both in vitro and in vivo models. This innovative compound demonstrated interference with the interaction between the spike protein of SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2). Furthermore, in vitro experiments showed that this compound downregulated the expression of ACE2 and transmembrane serine protease 2 (TMPRSS2). It also exhibited a reduction in the activity of 3-chymotrypsin-like protease (3CL) and RNA-dependent RNA polymerase (RdRp). Pretreatment with this small chromium (III)-based compound resulted in reduced ACE2-rich cell infection by various variants of SARS-CoV-2 spike protein-pseudotyped lentivirus. Finally, the compound effectively inhibited viral infection by multiple variants of SARS-CoV-2 spike protein-pseudotyped lentivirus in both the abdominal and thoracic regions of mice. In conclusion, this compound lowers the likelihood of SARS-CoV-2 entry into cells, inhibits viral maturation and replication in vitro, and reduces infection levels of multiple variants of SARS-CoV-2 spike protein-pseudotyped lentivirus in the abdomen and thorax following pretreatment. Small chromium (III)-based compounds have the potential to restrict the progression of SARS-CoV-2 infections.

Keywords: ACE2; COVID-19; Chromium (III)-Based compound; SARS-CoV-2; TMPRSS2.