xxx725a

Property	Value
?:abstract	Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. To screen for antiviral drugs for COVID-19 treatment, we constructed a SARS-CoV-2 spike (S) pseudovirus system using an HIV-1-based lentiviral vector with a luciferase reporter gene to screen 188 small potential antiviral compounds. Using this system, we identified nine compounds, specifically, bis-benzylisoquinoline alkaloids, that potently inhibited SARS-CoV-2 pseudovirus entry, with EC50 values of 0.1-10 M. Mechanistic studies showed that these compounds, reported as calcium channel blockers (CCBs), inhibited Ca2+-mediated membrane fusion and consequently suppressed coronavirus entry. These candidate drugs showed broad-spectrum efficacy against the entry of several coronavirus pseudotypes (SARS-CoV, MERS-CoV, SARS-CoV-2 [S-D614, S-G614, N501Y.V1 and N501Y.V2]) in different cell lines (293T, Calu-3, and A549). Antiviral tests using native SARS-CoV-2 in Vero E6 cells confirmed that four of the drugs (SC9/cepharanthine, SC161/hernandezine, SC171, and SC185/neferine) reduced cytopathic effect and supernatant viral RNA load. Among them, cepharanthine showed the strongest anti-SARS-CoV-2 activity. Collectively, this study offers new lead compounds for coronavirus antiviral drug discovery.
is ?:annotates of	<https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C0003451> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C0006684> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C0010827> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C0013227> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C0019704> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C0035736> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C0068486> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C0286921> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C1175743> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C1257876> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C1334435> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C1413097> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C1566558> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C3698360> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C4556170> <https://research.tib.eu/covid-19/entity/0xxx725a_hasAnnotation_C5203676>
?:creator	<https://research.tib.eu/covid-19/entity/He%2C_Chang-Long%3B_Huang%2C_Lu-Yi%3B_Wang%2C_Kai%3B_Gu%2C_Chen-Jian%3B_Hu%2C_Jie%3B_Zhang%2C_Gui-Ji%3B_Xu%2C_Wei%3B_Xie%2C_You-Hua%3B_Tang%2C_Ni%3B_Huang%2C_Ai-Long>
?:doi	<https://research.tib.eu/covid-19/entity/10.1101/2020.12.13.420406>
?:doi	10.1101/2020.12.13.420406
?:externalLink	<https://doi.org/10.1101/2020.12.13.420406>
?:journal	bioRxiv
?:license	cc-by-nc-nd
?:publication_isRelatedTo_Disease	<https://research.tib.eu/covid-19/entity/COVID-19>
is ?:relation_isRelatedTo_publication of	<https://research.tib.eu/covid-19/entity/0xxx725a_HAS_C0003451_TREATS_C5203670> <https://research.tib.eu/covid-19/entity/0xxx725a_HAS_C0013227_PREVENTS_C0010827> <https://research.tib.eu/covid-19/entity/0xxx725a_HAS_C5203676_CAUSES_C5203670>
?:source	BioRxiv; WHO
?:title	Identification of bis-benzylisoquinoline alkaloids as SARS-CoV-2 entry inhibitors from a library of natural products in vitro
?:type	<https://research.tib.eu/covid-19/vocab/Publication>
?:who_covidence_id	#420406
?:year	2020

Property

Value

?:abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. To screen for antiviral drugs for COVID-19 treatment, we constructed a SARS-CoV-2 spike (S) pseudovirus system using an HIV-1-based lentiviral vector with a luciferase reporter gene to screen 188 small potential antiviral compounds. Using this system, we identified nine compounds, specifically, bis-benzylisoquinoline alkaloids, that potently inhibited SARS-CoV-2 pseudovirus entry, with EC50 values of 0.1-10 M. Mechanistic studies showed that these compounds, reported as calcium channel blockers (CCBs), inhibited Ca2+-mediated membrane fusion and consequently suppressed coronavirus entry. These candidate drugs showed broad-spectrum efficacy against the entry of several coronavirus pseudotypes (SARS-CoV, MERS-CoV, SARS-CoV-2 [S-D614, S-G614, N501Y.V1 and N501Y.V2]) in different cell lines (293T, Calu-3, and A549). Antiviral tests using native SARS-CoV-2 in Vero E6 cells confirmed that four of the drugs (SC9/cepharanthine, SC161/hernandezine, SC171, and SC185/neferine) reduced cytopathic effect and supernatant viral RNA load. Among them, cepharanthine showed the strongest anti-SARS-CoV-2 activity. Collectively, this study offers new lead compounds for coronavirus antiviral drug discovery.

is ?:annotates of