The Analogs of Furanyl Methylidene Rhodanine Exhibit Broad-Spectrum Inhibitory and Inactivating Activities against Enveloped Viruses, including SARS-CoV-2 and Its Variants
Abstract
:1. Introduction
2. Materials and Methods
2.1. Synthesis and Characterization of Novel Furanyl Methylidene Rhodanine Analogs FD007–010 and FD012–013
2.2. Cells and Virus
2.3. Inhibition of Pseudovirus (PsV) Infection
2.4. Cytotoxicity
2.5. Inhibition of Authentic Virus Infection
2.6. Inactivation of Cell-Free Virions
2.7. Inhibition of HIV-1 6-HB Formation
2.8. Sucrose Density Gradient Assay to Evaluate Viral Inactivation
3. Results
3.1. Inhibitory and Inactivating Activity of FD001 and Analogs on Infection of SARS-CoV-2 and Its Variants
3.2. Inhibitory and Inactivating Activity of FD-Compounds on SARS-CoV and MERS-CoV Infection
3.3. FD-Compounds Effectively Inhibited Infection by Other Enveloped Viruses with Class I Viral Fusion Proteins
3.4. FD-Compounds Effectively Inhibited Infection by Enveloped Viruses with Class II and III Viral Fusion Protein, but Not Nonenveloped Virus Infection
3.5. FD-Compounds Exerted Antiviral Effects through Multiple Mechanisms of Action
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compounds | R | MW(Da) |
---|---|---|
FD001 | H | 470.0 |
FD007 | | 524.01 |
FD008 | | 568.06 |
FD009 | | 514.01 |
FD010 | | 594.07 |
FD012 | | 540.05 |
FD013 | | 582.11 |
Compound | CC50 (µM) | IC50 (µM) | SI | EC50 (µM) | SI |
---|---|---|---|---|---|
CC50/IC50 | CC50/EC50 | ||||
SARS-CoV PsV infection in hACE2-293T cells | |||||
FD001 | 28.84 ± 1.24 | 0.18 ± 0.02 | 160.22 | 1.58 ± 0.21 | 18.25 |
FD007 | 33.11 ± 1.02 | 0.11 ± 0.01 | 301.00 | 1.54 ± 0.14 | 21.50 |
FD008 | 23.44 ± 0.78 | 0.05 ± 0.01 | 468.80 | 0.19 ± 0.02 | 123.37 |
FD009 | 17.37 ± 0.64 | 0.03 ± 0.01 | 579.00 | 0.12 ± 0.01 | 144.75 |
FD010 | 20.42 ± 1.00 | 0.29 ± 0.03 | 70.41 | 0.19 ± 0.03 | 107.47 |
FD012 | 12.30 ± 0.34 | 0.02 ± 0.01 | 615.00 | 0.12 ± 0.01 | 102.50 |
FD013 | 18.62 ± 0.23 | 0.05 ± 0.01 | 372.40 | 0.10 ± 0.01 | 186.20 |
MERS-CoV PsV infection in Huh-7 cells | |||||
FD001 | 42.65 ± 1.31 | 0.29 ± 0.03 | 147.07 | 1.12 ± 0.16 | 38.08 |
FD007 | >50 | 0.20 ± 0.03 | >250 | 0.89 ± 0.09 | >56.18 |
FD008 | 38.90 ± 1.22 | 0.31 ± 0.02 | 125.48 | 0.69 ± 0.13 | 56.38 |
FD009 | 27.54 ± 1.43 | 0.28 ± 0.02 | 98.36 | 0.29 ± 0.02 | 94.97 |
FD010 | 44.67 ± 1.26 | 0.12 ± 0.01 | 372.25 | 0.04 ± 0.01 | 1116.75 |
FD012 | 18.62 ± 0.35 | 0.11 ± 0.01 | 169.27 | 0.05 ± 0.01 | 372.40 |
FD013 | 30.90 ± 0.63 | 0.05 ± 0.01 | 618.00 | 0.03 ± 0.01 | 1030.00 |
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Pu, J.; He, X.; Xu, W.; Wang, C.; Lan, Q.; Hua, C.; Wang, K.; Lu, L.; Jiang, S. The Analogs of Furanyl Methylidene Rhodanine Exhibit Broad-Spectrum Inhibitory and Inactivating Activities against Enveloped Viruses, including SARS-CoV-2 and Its Variants. Viruses 2022, 14, 489. https://doi.org/10.3390/v14030489
Pu J, He X, Xu W, Wang C, Lan Q, Hua C, Wang K, Lu L, Jiang S. The Analogs of Furanyl Methylidene Rhodanine Exhibit Broad-Spectrum Inhibitory and Inactivating Activities against Enveloped Viruses, including SARS-CoV-2 and Its Variants. Viruses. 2022; 14(3):489. https://doi.org/10.3390/v14030489
Chicago/Turabian StylePu, Jing, Xiaoyang He, Wei Xu, Cong Wang, Qiaoshuai Lan, Chen Hua, Kai Wang, Lu Lu, and Shibo Jiang. 2022. "The Analogs of Furanyl Methylidene Rhodanine Exhibit Broad-Spectrum Inhibitory and Inactivating Activities against Enveloped Viruses, including SARS-CoV-2 and Its Variants" Viruses 14, no. 3: 489. https://doi.org/10.3390/v14030489