Gemcitabine, lycorine and oxysophoridine inhibit novel coronavirus (SARS-CoV-2) in cell culture

Abstract

The emerging SARS-CoV-2 infection associated with the outbreak of viral pneumonia in China is ongoing worldwide. There are no approved antiviral therapies to treat this viral disease. Here we examined the antiviral abilities of three broad-spectrum antiviral compounds gemcitabine, lycorine and oxysophoridine against SARS-CoV-2 in cell culture. We found that all three tested compounds inhibited viral replication in Vero-E6 cells at noncytotoxic concentrations. The antiviral effect of gemcitabine was suppressed efficiently by the cytidine nucleosides. Additionally, combination of gemcitabine with oxysophoridine had an additive antiviral effect against SARS-CoV-2. Our results demonstrate that broad-spectrum antiviral compounds may have a priority for the screening of antiviral compounds against newly emerging viruses to control viral infection.

Potential Antiviral Options against SARS-CoV-2 Infection

“…The cell line is interferon-deficient; i.e., unlike normal mammalian cells, it does not secrete interferon alpha or beta when infected by viruses [34]. Moreover, this cell line was used routinely in anti-SARS-CoV-2 research [35][36][37][38].…”

Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections

“…Lycorine has also shown suppressive activity on in vitro viral replication of flaviviruses such as Japanese encephalitis, yellow fever, dengue-4, bunya, Punta Toro, Rift Valley fever, herpes simplex 1, and poliomyelitis viruses ( Gabrielsen et al, 1992 ; Hwang et al, 2008 ; Renard-Nozaki et al, 1989 ). Moreover, lycorine was reported to inhibit diverse coronavirus infections such as SARS-CoV, MERS-CoV, HCoV-NL63, and HCoV-OC43 both in vitro and in vivo ( Li et al, 2005 ; Shen et al, 2019 ), and recent studies in cell culture show lycorine's potent inhibition of SARS-CoV-2, the pathogen that causes the current COVID-19 pandemic ( Zhang et al, 2020 ); however, the mechanism of action of lycorine's antiviral activity still needs to be elucidated.…”

Identifying and repurposing antiviral drugs against severe acute respiratory syndrome coronavirus 2 with in silico and in vitro approaches

“…A known TMPRSS2 inhibitor, camostat, inhibited SARS-CoV-2 infection in Vero cells overexpressing TMPRSS2 [ 66 ]. Other approved antiviral drugs, including ivermectin, lopinavir, emetine, homoharringtonine, auranofin, gemcitabine, lycorine, oxysophoridine, suramin, nafamostat, obatoclax, salinomycin, amodiaquine, nelfinavir, mycophenolic acid, umifenovir, berberine, cyclosporine A, atazanavir, and artemisinin, were shown to inhibit SARS-CoV-2 propagation [ 63 , 64 , 67 , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] ]. Nelfinavir was also shown to inhibit SARS-CoV-2-induced membrane fusion in a virus-free cell model, using Vero cells overexpressing the Spike protein [ 78 ].…”