Structural basis of antiviral activity of caffeic acid against severe fever with thrombocytopenia syndrome virus |
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| Authors: | Motohiko Ogawa Yoshitaka Shirasago Isei Tanida Soichiro Kakuta Yasuo Uchiyama Masayuki Shimojima Kentaro Hanada Masayuki Saijo Masayoshi Fukasawa |
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| Affiliation: | 1. Department of Virology I, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan;2. Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan;3. Department of Cellular and Molecular Neuropathology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, 113-8421, Japan;4. Laboratory of Morphology and Image Analysis, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan;1. Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan;2. Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan;3. Laboratory of Medical Microbiology, Graduate School of Pharmacy, Nihon University, Japan;4. Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan;5. Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital, Okayama, Japan;6. Division of Infectious Diseases, Department of Medical Subspecialties, National Center for Child Health and Development, Tokyo, Japan;7. Department of Urology, The Jikei University Katsushika Medical Center, Tokyo, Japan;8. Departments of Infectious Diseases, National Cancer Center Hospital, Tokyo, Japan;1. Department of Nephrology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan;2. Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan;3. Division of Infection Control and Prevention, University of Fukui Hospital, Fukui, Japan;4. Department of Internal Medicine, National Hospital Organization Awara Hospital, Fukui, Japan;5. Department of Infection Control and Prevention, Kyoto Prefectural University Medicine, Kyoto, Japan;1. Department of Infection Control and Prevention, Osaka City University Hospital, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka, 545-8585, Japan;2. Department of Infection Control Science, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka, 545-8585, Japan;3. Research Center for Infectious Diseases, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka, 545-8585, Japan;4. Bacteriology, Osaka City University Hospital, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka, 545-8585, Japan;1. Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand;2. Department of Mathematics, Faculty of Science, Naresuan University, Phitsanulok, 65000, Thailand;3. Department of Medicine, Faculty of Medicine, Naresuan University, Phitsanulok, 65000, Thailand;4. Buddhachinaraj Hospital, Phitsanulok, 65000, Thailand |
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| Abstract: | Caffeic acid (CA), a coffee-related natural compound, has various beneficial biological effects, including antiviral effects. Our former studies demonstrated that the CA dose-dependently inhibited the in vitro infection with Dabie bandavirus, which was previously named as severe fever with thrombocytopenia syndrome virus (SFTSV), mainly at the step of virus attachment. Therefore, we studied the structural basis of CA for conferring anti-SFTSV activity to clarify the mechanism of action of CA against SFTSV. In this study, the anti-SFTSV activity of nine CA analogs were examined. The treatment of SFTSV with the 3,4-dihydroxyhydrocinnamic acid (DHCA) as well as CA inhibited the SFTSV infection in a dose-dependent manner, whereas other CA analogs did not. Both CA and DHCA only possessed the o-dihydroxybenzene backbone. When SFTSV was treated with catechol (o-dihydroxybenzene), SFTSV infection was also dose-dependently inhibited. Additionally, four compounds having the o-dihydroxybenzene backbone; CA phenethyl ester, methyl CA, 3,4-dihydroxyphenylacetic acid, and 3,4-dihydroxybenzoic acid, dose-dependently inhibited the viral infection, although these compounds were more toxic or less effective than CA. In conclusion, the o-dihydroxybenzene backbone in CA and its analogs was a critical structure for the anti-SFTSV activity. Based on these findings, modifications of the o-dihydroxybenzene backbone with various other residues might improve the antiviral effect and cytotoxicity for SFTSV. |
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| Keywords: | Caffeic acid 3, 4-Dihydroxyhydrocinnamic acid Antiviral activity SFTS CA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0045" }," $$" :[{" #name" :" text" ," _" :" caffeic acid DHCA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0055" }," $$" :[{" #name" :" text" ," _" :" 3, 4-dihydroxyhydrocinnamic acid SFTSV" },{" #name" :" keyword" ," $" :{" id" :" kwrd0065" }," $$" :[{" #name" :" text" ," _" :" severe fever with thrombocytopenia syndrome virus the half-maximal inhibitory concentration the half-maximal cytotoxic concentration SI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0095" }," $$" :[{" #name" :" text" ," _" :" the selectivity index MOI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0105" }," $$" :[{" #name" :" text" ," _" :" multiplicity of infection SD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0115" }," $$" :[{" #name" :" text" ," _" :" standard deviation |
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