Multidrug treatment with nelfinavir and cepharanthine against COVID-19

Ohashi, H.; Watashi, K.; Saso, W.; Shionoya, K.; Iwanami, S.; Hirokawa, T.; Shirai, T.; Kanaya, S.; Ito, Y.; Kim, K. S.; Nishioka, K.; Ando, S.; Ejima, K.; Koizumi, Y.; Tanaka, T.; Aoki, S.; Kuramochi, K.; Suzuki, T.; Maenaka, K.; Matano, T.; Muramatsu, M.; Saijo, M.; Aihara, K.; Iwami, S.; Takeda, M.; McKeating, J.; Wakita, T.

doi:10.1101/2020.04.14.039925

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bioRxiv · 10.1101/2020.04.14.039925

Multidrug treatment with nelfinavir and cepharanthine against COVID-19

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Abstract

Antiviral treatments targeting the emerging coronavirus disease 2019 (COVID-19) are urgently required. We screened a panel of already-approved drugs in a cell culture model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and identified two new antiviral agents: the HIV protease inhibitor Nelfinavir and the anti-inflammatory drug Cepharanthine. In silico modeling shows Nelfinavir binds the SARS-CoV-2 main protease consistent with its inhibition of viral replication, whilst Cepharanthine inhibits viral attachment and entry into cells. Consistent with their different modes of action, in vitro assays highlight a synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation. Mathematical modeling in vitro antiviral activity coupled with the known pharmacokinetics for these drugs predicts that Nelfinavir will facilitate viral clearance. Combining Nelfinavir/Cepharanthine enhanced their predicted efficacy to control viral proliferation, to ameliorate both the progression of disease and risk of transmission. In summary, this study identifies a new multidrug combination treatment for COVID-19.

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Ohashi, H., Watashi, K., Saso, W., Shionoya, K., Iwanami, S., Hirokawa, T., Shirai, T., Kanaya, S., Ito, Y., Kim, K. S., Nishioka, K., Ando, S., Ejima, K., Koizumi, Y., Tanaka, T., Aoki, S., Kuramochi, K., Suzuki, T., Maenaka, K., Matano, T., Muramatsu, M., Saijo, M., Aihara, K., Iwami, S., Takeda, M., McKeating, J., Wakita, T.. 2020-04-15. Multidrug treatment with nelfinavir and cepharanthine against COVID-19. https://doi.org/10.1101/2020.04.14.039925

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