We
performed density functional theory (DFT) calculations for ribonucleotides and
active triphosphate metabolites of candidate drugs against Coronavirus disease
2019 (Covid-19). Frontier orbitals (highest occupied molecular orbital and
lowest unoccupied molecularorbital)
at optimized structure of each molecule were obtained. T-705RTP (active triphosphate
metabolite of favipiravir) and cytidine triphosphate (CTP) have similar shapes
of frontier orbitals. We also obtained similar shapes of frontier orbitals
among dihydroxy GS-441524 triphosphate (GS-441524 is an active triphosphate
metabolite of remdesivir) and adenosine triphosphate (ATP). From a theoretical viewpoint, we suggest T-705RTP is a CTP analogue
and dihydroxy GS-441524 triphosphate is anATP analogue.
References
[1]
Wu, F., Zhao, S., Yu, B., Chen, Y., Wang, W., Song, Z., Hu, Y., Tao, Z., Tian, J., Pei, Y., Yuan, M., Zhang, Y., Dai, F., Liu, Y., Wang, Q., Zheng, J., Xu, L., Holmes, E.C. and Zhang, Y. (2020) A New Coronavirus Associated with Human Respiratory Disease in China. Nature, 579, 265-269. https://doi.org/10.1038/s41586-020-2008-3
[2]
Gao, Y., Yan, L., Huang, Y., Liu, F., Zhao, Y., Cao, L., Wang, T., Sun, Q., Ming, Z., Zhang, L., Ge, J., Zheng, L., Zhang, Y., Wang, H., Zhu, Y., Zhu, C., Hu, T., Hua, T., Zhang, B., Yang, X., Li, J., Yang, H., Liu, Z., Xu, W., Guddat, L.W., Wang, Q., Lou, Z. and Rao, Z. (2020) Structure of the RNA-Dependent RNA Polymerase from COVID-19 Virus. Science, eabb7498. https://doi.org/10.1126/science.abb7498
[3]
Shiraki, K. and Daikoku, T. (2020) Favipiravir, an Anti-Influenza Drug against Life-Threatening RNA Virus Infections. Pharmacology & Therapeutics, 209, Article ID: 107512. https://doi.org/10.1016/j.pharmthera.2020.107512
[4]
Furuta, Y., Takahashi, K., Kuno-Maekawa, M., Sangawa, H., Uehara, S., Kozaki, K., Nomura, N., Egawa, H. and Shiraki, K. (2005) Mechanism of Action of T-705 against Influenza Virus. Antimicrobial Agents and Chemotherapy, 49, 981-986. https://doi.org/10.1128/AAC.49.3.981-986.2005
[5]
Warren, T.K., Jordan, R., Lo, M.K., Ray, A.S., Mackman, R.L., Soloveva, V., Siegel, D., Perron, M., Bannister, R., Hui, H.C., Larson, N., Strickley, R., Wells, J., Stuthman1, K.S., Van Tongeren1, S.A., Garza, N.L., Donnelly, G., Shurtleff, A.C., Retterer, C.J., Gharaibeh, D., Zamani, R., Kenny, T., Eaton1, B.P., Grimes, E., Welch, L.S., Gomba, L., Wilhelmsen, C.L., Nichols, D.K., Nuss, J.E., Nagle, E.R., Kugelman, J.R., Palacios, G., Doerffler, E., Neville, S., Carra, E., Clarke, M.O., Zhang, L., Lew, W., Ross, B., Wang, Q., Chun, K., Wolfe, L., Babusis, D., Park, Y., Stray, K.M., Trancheva, I., Feng, J.Y., Barauskas, O., Xu, Y., Wong, P., Braun, M.R., Flint, M., McMullan, L.K., Chen, S., Fearns, R., Swaminathan, S., Mayers, D.L., Spiropoulou, C.F., Lee, W.A., Nichol, S.T., Cihlar, T. and Bavari, S. (2016) Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola Virus in Rhesus Monkeys. Nature, 531, 381-385. https://doi.org/10.1038/nature17180
[6]
Cai, Q., Yang, M., Liu, D., Chen, J., Shu, D., Xia, J., Liao, X., Gu, Y., Cai, Q., Yang, Y., Shen, C., Li, X., Peng, L., Huang, D., Zhang, J., Zhang, S., Wang, F., Liu, J., Chen, L., Chen, S., Wang, Zhang, Z., Cao, R., Zhong, W., Liu, Y. and Liu, L. (2020) Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering. (In Press) https://doi.org/10.1016/j.eng.2020.03.007
[7]
Wang, M., Cao, R., Zhang, L., Yang, X., Liu, J., Xu, M., Shi, Z., Hu, Z., Zhong, W. and Xiao, G. (2020) Remdesivir and Chloroquine Effectively Inhibit the Recently Emerged Novel Coronavirus (2019-nCoV) in Vitro. Cell Research, 30, 269-271. https://doi.org/10.1038/s41422-020-0282-0
[8]
Neogi, U., Hill, K.J., Ambikan, A.T., Heng, X., Quinn, T.P., Byrareddy, S.N., Sönnerborg, A., Sarafianos, S.G. and Singh, K. (2020) Feasibility of Known RNA Polymerase Inhibitors as Anti-SARS-CoV-2 Drugs. Pathogens, 9, 320-335. https://doi.org/10.3390/pathogens9050320
[9]
Fukui, K. and Fujimoto, H. (1997) Frontier Orbitals and Reaction Paths: Selected Papers of Kenichi Fukui. World Scientific Series in 20th Century Chemistry, Volume 7. World Scientific Publishing Co., Singapore. https://doi.org/10.1142/2731
[10]
Mizukami, Y. (2004) Frontier Electron Density Pattern of Dioxin Congeners. Chemistry Letters, 33, 1328-1329. https://doi.org/10.1246/cl.2004.1328
[11]
Mizukami, Y. (2015) Characters of Frontier Orbitals of Antiviral Drugs. Memoirs of the Faculty of Education, Shiga University (Natural Science), 64, 141-144. https://www.edu.shiga-u.ac.jp/~mizukami/papers/paper-2014-11-11.pdf
[12]
Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G.A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H.P., Izmaylov, A.F., Bloino, J., Zheng, G., Sonnenberg, J.L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery Jr., J.A., Peralta, J.E., Ogliaro, F., Bearpark, M., Heyd, J.J., Brothers, E., Kudin, K.N., Staroverov, V.N., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J.C., Iyengar, S.S., Tomasi, J., Cossi, M., Rega, N., Millam, J.M., Klene, M., Knox, J.E., Cross, J.B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R.E., Yazyev, O., Austin, A.J., Cammi, R., Pomelli, C., Ochterski, J.W., Martin, R.L., Morokuma, K., Zakrzewski, V.G., Voth, G.A., Salvador, P., Dannenberg, J.J., Dapprich, S., Daniels, A.D., Farkas, O., Foresman, J.B., Ortiz, J.V., Cioslowski, J. and Fox, D.J. (2009) Gaussian 09, Revision A.02. Gaussian Inc., Wallingford.
[13]
Stowasser, R. and Hoffmann, R. (1999) What Do the Kohn-Sham Orbitals and Eigenvalues Mean? Journal of the American Chemical Society, 121, 3414-3420. https://doi.org/10.1021/ja9826892
[14]
Jin, Z., Tucker, K., Lin, X., Kao, C.C., Shaw, K., Tan, H., Symons, J., Behera, I., Rajwanshi, V.K., Dyatkina, N., Wang, G., Beigelman, L. and Deval, J. (2015) Biochemical Evaluation of the Inhibition Properties of Favipiravir and 2’-C-Methyl-Cytidine Triphosphates against Human and Mouse Norovirus RNA Polymerases. Antimicrobial Agents and Chemotherapy, 59, 7504-7516. https://doi.org/10.1128/AAC.01391-15
[15]
Akaike, T. (2001) Role of Free Radicals in Viral Pathogenesis and Mutation. Reviews in Medical Virology, 11, 87-101. https://doi.org/10.1002/rmv.303
