Potential anti-COVID-19 agents, cepharanthine and nelfinavir, and their usage for combination treatment.

Abstract

Antiviral treatments targeting the coronavirus disease 2019 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 agents having higher antiviral potentials than the drug candidates such as remdesivir and chroloquine in VeroE6/TMPRSS2 cells: the anti-inflammatory drug cepharanthine and human immunodeficiency virus protease inhibitor nelfinavir. Cepharanthine inhibited SARS-CoV-2 entry through the blocking of viral binding to target cells, while nelfinavir suppressed viral replication partly by protease inhibition. Consistent with their different modes of action, synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation was highlighted. Mathematical modeling in vitro antiviral activity coupled with the calculated total drug concentrations in the lung predicts that nelfinavir will shorten the period until viral clearance by 4.9 days and the combining cepharanthine/nelfinavir enhanced their predicted efficacy. These results warrant further evaluation of the potential anti-SARS-CoV-2 activity of cepharanthine and nelfinavir.

• Authors: 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
• Journal: iScience (iScience) Vol. 24 Issue 4 Pg. 102367 (Apr 23 2021) ISSN: 2589-0042 [Electronic] United States
• PMID: 33817567 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors.