Potential anti-COVID-19 agents, cepharanthine and nelfinavir, and their usage for combination treatment
Hirofumi Ohashi, Koichi Watashi, Wakana Saso, Kaho Shionoya, Shoya Iwanami, Takatsugu Hirokawa, Tsuyoshi Shirai, Shigehiko Kanaya, Yusuke Ito, Kwang Su Kim, Takao Nomura, Tateki Suzuki, Kazane Nishioka, Shuji Ando, Keisuke Ejima, Yoshiki Koizumi, Tomohiro Tanaka, Shin Aoki, Kouji Kuramochi, Tadaki Suzuki, Takao Hashiguchi, Katsumi Maenaka, Tetsuro Matano, Masamichi Muramatsu, Masayuki Saijo, Kazuyuki Aihara, Shingo Iwami, Makoto Takeda, Jane A Mckeating, Takaji Wakita
iScience, doi:10.1016/j.isci.2021.102367
Nelfinavir (NFV) inhibits SARS-CoV-2 replication Cepharanthine (CEP) inhibits SARS-CoV-2 attachment to target cells Combination of NFV and CEP can synergistically augment antiviral
METHODS All methods can be found in the accompanying transparent methods supplemental file. Figure 6 . Combination treatment with CEP and NFV (A) Dose-response curve of CEP/NFV co-treatment in the infection experiment (MOI = 0.001). Extracellular viral RNA levels at 24 hr after infection were quantified and plotted against concentrations of CEP (0.78, 1.25, 2.00, 3.20, and 5.12 mM: 1.6-fold serial dilution) and NFV (1.08, 1.30, 1.56, 1.87, and 2.24 mM: 1.2-fold serial dilution). (B) Cell viability upon co-treatment with compounds. (C) The three-dimensional interaction landscapes of CEP and NFV were evaluated based on the Bliss independence model. Red and blue colors on the contour plot indicate synergy and antagonism, respectively. These data were from three independent experiments (A, B; mean G SD).
AUTHOR CONTRIBUTIONS Conceptualization, K.W.; investigation, H.O., K.W., W.S., K.S., S. Iwanami, T.H., T. Shirai., S.K., Y.I., K.S.K., T.N., Tateki Suzuki, K.N., and S. Iwami; methodology and resources, S.Ando., Tadaki Suzuki., T.H., K.M., M.S., M.T., T.W.; analysis, all the authors; writing and editing, K.W., T.H., K.A., S. Iwami, and J.A.M; funding acquisition, K.W. and M.T.; supervision, K.W.
DECLARATION OF INTERESTS The authors declare no competing interests. iScience, Volume 24
Supplemental information Potential anti-COVID-19 agents, cepharanthine and nelfinavir, and their usage for combination treatment Hirofumi Ohashi, Koichi Watashi, Wakana Saso, Kaho Shionoya,..
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