PT  - JOURNAL ARTICLE
AU  - Hirofumi Ohashi
AU  - Koichi Watashi
AU  - Wakana Saso
AU  - Kaho Shionoya
AU  - Shoya Iwanami
AU  - Takatsugu Hirokawa
AU  - Tsuyoshi Shirai
AU  - Shigehiko Kanaya
AU  - Yusuke Ito
AU  - Kwang Su Kim
AU  - Kazane Nishioka
AU  - Shuji Ando
AU  - Keisuke Ejima
AU  - Yoshiki Koizumi
AU  - Tomohiro Tanaka
AU  - Shin Aoki
AU  - Kouji Kuramochi
AU  - Tadaki Suzuki
AU  - Katsumi Maenaka
AU  - Tetsuro Matano
AU  - Masamichi Muramatsu
AU  - Masayuki Saijo
AU  - Kazuyuki Aihara
AU  - Shingo Iwami
AU  - Makoto Takeda
AU  - Jane A. McKeating
AU  - Takaji Wakita
TI  - Multidrug treatment with nelfinavir and cepharanthine against COVID-19
AID  - 10.1101/2020.04.14.039925
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.14.039925
4099  - http://biorxiv.org/content/early/2020/04/15/2020.04.14.039925.short
4100  - http://biorxiv.org/content/early/2020/04/15/2020.04.14.039925.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.