Exploring Novel Vitamin K Derivatives with Anti-SARS-CoV-2 Activity

Taiki Homma; Mika Okamoto; Ryohto Koharazawa; Mayu Hayakawa; Taiki Fushimi; Chisato Tode; Yoshihisa Hirota; Naomi Osakabe; Masanori Baba; Yoshitomo Suhara

doi:10.1021/acsomega.3c04175

Exploring Novel Vitamin K Derivatives with Anti-SARS-CoV-2 Activity

ACS Omega. 2023 Nov 1;8(45):42248-42263. doi: 10.1021/acsomega.3c04175. eCollection 2023 Nov 14.

Authors

Taiki Homma¹, Mika Okamoto², Ryohto Koharazawa¹, Mayu Hayakawa¹, Taiki Fushimi³, Chisato Tode⁴, Yoshihisa Hirota^{1

3}, Naomi Osakabe^{1

3}, Masanori Baba², Yoshitomo Suhara^{1

3}

Affiliations

¹ Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
² Division of Infection Control Research, Center for Advanced Science Research and Promotion, Kagoshima University, Kagoshima 890-8580, Japan.
³ Functional Control Systems, Graduate School of Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
⁴ Instrumental Analysis Center, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.

Abstract

From our compound library of vitamin K derivatives, we found that some compounds exhibited anti-SARS-CoV-2 activity in VeroE6/TMPRSS2 cells. The common structure of these compounds was menaquinone-2 (MK-2) with either the m-methylphenyl or the 1-naphthyl group introduced at the end of the side chain. Therefore, new vitamin K derivatives having more potent anti-SARS-CoV-2 activity were explored by introducing various functional groups at the ω-position of the side chain. MK-2 derivatives with a purine moiety showed the most potent antiviral activity among the derivatives. We also found that their mechanism of action was the inhibition of RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. The chemical structures of our compounds were completely different from those of nucleic acid derivatives such as remdesivir and molnupiravir, clinically approved RdRp inhibitors for COVID-19 treatment, suggesting that our compounds may be effective against viruses resistant to these nucleic acid derivatives.