Griffithsin with A Broad-Spectrum Antiviral Activity by Binding Glycans in Viral Glycoprotein Exhibits Strong Synergisti
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LETTER
Griffithsin with A Broad-Spectrum Antiviral Activity by Binding Glycans in Viral Glycoprotein Exhibits Strong Synergistic Effect in Combination with A Pan-Coronavirus Fusion Inhibitor Targeting SARS-CoV-2 Spike S2 Subunit Yanxing Cai1 • Wei Xu1 • Chenjian Gu1 • Xia Cai1 • Di Qu1 • Lu Lu1 • Youhua Xie1
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Shibo Jiang1
Received: 12 August 2020 / Accepted: 10 September 2020 Ó Wuhan Institute of Virology, CAS 2020
Dear Editor, The pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed a significant threat to global public health and economy, thus calling for the rapid development of effective therapeutics and prophylactics. Repurposing existing medicines with clinical safety profiles offers a more rapid hope of combating COVID-19 pandemic than developing a new therapeutic. For example, remdesivir was originally developed to treat Ebola virus infection and its safety to humans has been confirmed in a phase I clinical trial (Grein et al. 2020). Therefore, it immediately went to clinical trials for in vivo efficacy in treatment of COVID-19 patients after its in vitro antiSARS-CoV-2 activity was verified (Grein et al. 2020). In this study, we tested the in vitro inhibitory activity of griffithsin (GRFT) against infection of pseudotyped and live SARS-CoV-2 infection, in order to repurpose the application of GRFT as a potential prophylactic or therapeutic to prevent or treat COVID-19. GRFT, a lectin isolated from the red alga Griffithsia sp, can recognize mannose with high affinity and has a broad-spectrum antiviral activity (Lusvarghi and Bewley 2016). GRFT is
Yanxing Cai, Wei Xu and Chenjian Gu have contributed equally to this work.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12250-020-00305-3) contains supplementary material, which is available to authorized users. & Shibo Jiang [email protected] & Youhua Xie [email protected] 1
Key Laboratory of Medical Molecular Virology (MOE/NHC/ CAMS), School of Basic Medical Sciences and BSL-3 Facility, Fudan University, Shanghai 200032, China
safe to human as demonstrated in the phase I clinical trial of GRFT as an anti-HIV microbicide for prevention of sexual transmission of HIV in healthy populations, in which the single-dose open-label design and the multipledose, randomized design have been performed with treatment duration of 14 days and 30 subjects enrolled (Lee 2019). We first performed SARS-CoV-2 pseudovirus infection assay (Xia et al. 2020) to evaluate the activity of GRFT against SARS-CoV-2 in vitro. As shown in Fig. 1A, GRFT could significantly inhibit SARS-CoV-2 pseudovirus infection in a dose-dependent manner with the half maximal inhibitory concentration (IC50) of 293 nmol/L. To further confirm this result, we then assessed its inhibitory activity against live SARS-CoV-2 infection with immunofluorescence and qRT-PCR assays. As shown in Fig. 1B and 1C, GRFT inhibited live SARS-CoV-2 infection
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