Berbamine hydrochloride potently inhibits SARS-CoV-2 infection by blocking S protein-mediated membrane fusion
COVID-19 caused by SARS-CoV-2 has posed a significant threat to global public health since its outbreak in late 2019. Although there are a few drugs approved for clinical treatment to combat SARS-CoV-2 infection currently, the severity of the ongoing global pandemic still urges the efforts to discov...
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| Veröffentlicht in: | PLoS neglected tropical diseases 2022-04, Vol.16 (4), p.e0010363-e0010363 |
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| container_title | PLoS neglected tropical diseases |
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| creator | Zhang, Zhe-Rui Zhang, Ya-Nan Zhang, Hong-Qing Zhang, Qiu-Yan Li, Na Li, Qi Deng, Cheng-Lin Zhang, Bo Li, Xiao-Dan Ye, Han-Qing |
| description | COVID-19 caused by SARS-CoV-2 has posed a significant threat to global public health since its outbreak in late 2019. Although there are a few drugs approved for clinical treatment to combat SARS-CoV-2 infection currently, the severity of the ongoing global pandemic still urges the efforts to discover new antiviral compounds. As the viral spike (S) protein plays a key role in mediating virus entry, it becomes a potential target for the design of antiviral drugs against COVID-19. Here, we tested the antiviral activity of berbamine hydrochloride, a bis-benzylisoquinoline alkaloid, against SARS-CoV-2 infection. We found that berbamine hydrochloride could efficiently inhibit SARS-CoV-2 infection in different cell lines. Further experiments showed berbamine hydrochloride inhibits SARS-CoV-2 infection by targeting the viral entry into host cells. Moreover, berbamine hydrochloride and other bis-benzylisoquinoline alkaloids could potently inhibit S-mediated cell-cell fusion. Furthermore, molecular docking results implied that the berbamine hydrochloride could bind to the post fusion core of SARS-CoV-2 S2 subunit. Therefore, berbamine hydrochloride may represent a potential efficient antiviral agent against SARS-CoV-2 infection. |
| doi_str_mv | 10.1371/journal.pntd.0010363 |
| format | Article |
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Although there are a few drugs approved for clinical treatment to combat SARS-CoV-2 infection currently, the severity of the ongoing global pandemic still urges the efforts to discover new antiviral compounds. As the viral spike (S) protein plays a key role in mediating virus entry, it becomes a potential target for the design of antiviral drugs against COVID-19. Here, we tested the antiviral activity of berbamine hydrochloride, a bis-benzylisoquinoline alkaloid, against SARS-CoV-2 infection. We found that berbamine hydrochloride could efficiently inhibit SARS-CoV-2 infection in different cell lines. Further experiments showed berbamine hydrochloride inhibits SARS-CoV-2 infection by targeting the viral entry into host cells. Moreover, berbamine hydrochloride and other bis-benzylisoquinoline alkaloids could potently inhibit S-mediated cell-cell fusion. Furthermore, molecular docking results implied that the berbamine hydrochloride could bind to the post fusion core of SARS-CoV-2 S2 subunit. Therefore, berbamine hydrochloride may represent a potential efficient antiviral agent against SARS-CoV-2 infection.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0010363</identifier><identifier>PMID: 35468133</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alkaloids ; Antiviral activity ; Antiviral agents ; Antiviral Agents - pharmacology ; Benzylisoquinolines - pharmacology ; Biology and life sciences ; Cell fusion ; Cell lines ; Coronaviruses ; COVID-19 ; COVID-19 - drug therapy ; Cytotoxicity ; Disease transmission ; Dosage and administration ; Drug development ; Drugs ; Experiments ; FDA approval ; Fusion protein ; Genomes ; Health ; Humans ; Infections ; Laboratories ; Medicine and health sciences ; Membrane Fusion ; Membrane proteins ; Molecular docking ; Molecular Docking Simulation ; Pandemics ; Physical Sciences ; Proteins ; Public health ; Research and Analysis Methods ; RNA polymerase ; SARS-CoV-2 ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Spike Glycoprotein, Coronavirus ; Tropical diseases ; Viral diseases ; Virology ; Virus Internalization ; Viruses</subject><ispartof>PLoS neglected tropical diseases, 2022-04, Vol.16 (4), p.e0010363-e0010363</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 Zhang et al 2022 Zhang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-cb0ac19c957952a9813822a58f0cb93c14d5b6426adaf9abdda6375beeaba90e3</citedby><cites>FETCH-LOGICAL-c624t-cb0ac19c957952a9813822a58f0cb93c14d5b6426adaf9abdda6375beeaba90e3</cites><orcidid>0000-0001-7770-4071</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071123/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071123/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35468133$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kamel, Mohamed Gomaa</contributor><creatorcontrib>Zhang, Zhe-Rui</creatorcontrib><creatorcontrib>Zhang, Ya-Nan</creatorcontrib><creatorcontrib>Zhang, Hong-Qing</creatorcontrib><creatorcontrib>Zhang, Qiu-Yan</creatorcontrib><creatorcontrib>Li, Na</creatorcontrib><creatorcontrib>Li, Qi</creatorcontrib><creatorcontrib>Deng, Cheng-Lin</creatorcontrib><creatorcontrib>Zhang, Bo</creatorcontrib><creatorcontrib>Li, Xiao-Dan</creatorcontrib><creatorcontrib>Ye, Han-Qing</creatorcontrib><title>Berbamine hydrochloride potently inhibits SARS-CoV-2 infection by blocking S protein-mediated membrane fusion</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>COVID-19 caused by SARS-CoV-2 has posed a significant threat to global public health since its outbreak in late 2019. Although there are a few drugs approved for clinical treatment to combat SARS-CoV-2 infection currently, the severity of the ongoing global pandemic still urges the efforts to discover new antiviral compounds. As the viral spike (S) protein plays a key role in mediating virus entry, it becomes a potential target for the design of antiviral drugs against COVID-19. Here, we tested the antiviral activity of berbamine hydrochloride, a bis-benzylisoquinoline alkaloid, against SARS-CoV-2 infection. We found that berbamine hydrochloride could efficiently inhibit SARS-CoV-2 infection in different cell lines. Further experiments showed berbamine hydrochloride inhibits SARS-CoV-2 infection by targeting the viral entry into host cells. Moreover, berbamine hydrochloride and other bis-benzylisoquinoline alkaloids could potently inhibit S-mediated cell-cell fusion. Furthermore, molecular docking results implied that the berbamine hydrochloride could bind to the post fusion core of SARS-CoV-2 S2 subunit. Therefore, berbamine hydrochloride may represent a potential efficient antiviral agent against SARS-CoV-2 infection.</description><subject>Alkaloids</subject><subject>Antiviral activity</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - pharmacology</subject><subject>Benzylisoquinolines - pharmacology</subject><subject>Biology and life sciences</subject><subject>Cell fusion</subject><subject>Cell lines</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - drug therapy</subject><subject>Cytotoxicity</subject><subject>Disease transmission</subject><subject>Dosage and administration</subject><subject>Drug development</subject><subject>Drugs</subject><subject>Experiments</subject><subject>FDA approval</subject><subject>Fusion protein</subject><subject>Genomes</subject><subject>Health</subject><subject>Humans</subject><subject>Infections</subject><subject>Laboratories</subject><subject>Medicine and health sciences</subject><subject>Membrane Fusion</subject><subject>Membrane proteins</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Pandemics</subject><subject>Physical Sciences</subject><subject>Proteins</subject><subject>Public health</subject><subject>Research and Analysis Methods</subject><subject>RNA polymerase</subject><subject>SARS-CoV-2</subject><subject>Severe acute respiratory syndrome</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Spike Glycoprotein, Coronavirus</subject><subject>Tropical diseases</subject><subject>Viral diseases</subject><subject>Virology</subject><subject>Virus Internalization</subject><subject>Viruses</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNptUl2L1DAULaK46-o_EC0I4kvHfDSd5kUYBz8WFgRHfQ03H51mTJvZpBXm35s63WVGlj6k3Jxz7r0nJ8teYrTAdInf7_wYenCLfT_oBUIY0Yo-yi4xp6wgS8oen_xfZM9i3CHEOKvx0-yCsrKqMaWXWffRBAmd7U3eHnTwqnU-WG3yvR9MP7hDbvvWSjvEfLP6vinW_ldBUq0xarC-z-Uhl86r37bf5pt8HxLL9kVntIXB6LwznQyQxJsxJvjz7EkDLpoX83mV_fz86cf6a3Hz7cv1enVTqIqUQ6EkAoW54mzJGQGeRq0JAVY3SElOFS41k1VJKtDQcJBaQ0WXTBoDEjgy9Cp7fdTdOx_F7FQUpKoYpozzOiGujwjtYSf2wXYQDsKDFf8KPmwFhMEqZ0QDTclKpRQluKSM1Aq45sntmpaIMpS0PszdRpk2V8m3AO5M9Pymt63Y-j-CoyXGhCaBd7NA8LejiYPobFTGueScH6e5GWMVxuXU681_0Ie3m1FbSAuk1_Kpr5pExWqJCONJakItHkClT5vOKt-bxqb6GeHtCaE14IY2ejdOSYjnwPIIVMHHGExzbwZGYkrv3dRiSq-Y05tor06NvCfdxZX-BdpW7F4</recordid><startdate>20220401</startdate><enddate>20220401</enddate><creator>Zhang, Zhe-Rui</creator><creator>Zhang, Ya-Nan</creator><creator>Zhang, Hong-Qing</creator><creator>Zhang, Qiu-Yan</creator><creator>Li, Na</creator><creator>Li, Qi</creator><creator>Deng, Cheng-Lin</creator><creator>Zhang, Bo</creator><creator>Li, Xiao-Dan</creator><creator>Ye, Han-Qing</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-7770-4071</orcidid></search><sort><creationdate>20220401</creationdate><title>Berbamine hydrochloride potently inhibits SARS-CoV-2 infection by blocking S protein-mediated membrane fusion</title><author>Zhang, Zhe-Rui ; Zhang, Ya-Nan ; Zhang, Hong-Qing ; Zhang, Qiu-Yan ; Li, Na ; Li, Qi ; Deng, Cheng-Lin ; Zhang, Bo ; Li, Xiao-Dan ; Ye, Han-Qing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-cb0ac19c957952a9813822a58f0cb93c14d5b6426adaf9abdda6375beeaba90e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Alkaloids</topic><topic>Antiviral activity</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - pharmacology</topic><topic>Benzylisoquinolines - pharmacology</topic><topic>Biology and life sciences</topic><topic>Cell fusion</topic><topic>Cell lines</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>COVID-19 - drug therapy</topic><topic>Cytotoxicity</topic><topic>Disease transmission</topic><topic>Dosage and administration</topic><topic>Drug development</topic><topic>Drugs</topic><topic>Experiments</topic><topic>FDA approval</topic><topic>Fusion protein</topic><topic>Genomes</topic><topic>Health</topic><topic>Humans</topic><topic>Infections</topic><topic>Laboratories</topic><topic>Medicine and health sciences</topic><topic>Membrane Fusion</topic><topic>Membrane proteins</topic><topic>Molecular docking</topic><topic>Molecular Docking Simulation</topic><topic>Pandemics</topic><topic>Physical Sciences</topic><topic>Proteins</topic><topic>Public health</topic><topic>Research and Analysis Methods</topic><topic>RNA polymerase</topic><topic>SARS-CoV-2</topic><topic>Severe acute respiratory syndrome</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Spike Glycoprotein, Coronavirus</topic><topic>Tropical diseases</topic><topic>Viral diseases</topic><topic>Virology</topic><topic>Virus Internalization</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Zhe-Rui</creatorcontrib><creatorcontrib>Zhang, Ya-Nan</creatorcontrib><creatorcontrib>Zhang, Hong-Qing</creatorcontrib><creatorcontrib>Zhang, Qiu-Yan</creatorcontrib><creatorcontrib>Li, Na</creatorcontrib><creatorcontrib>Li, Qi</creatorcontrib><creatorcontrib>Deng, Cheng-Lin</creatorcontrib><creatorcontrib>Zhang, Bo</creatorcontrib><creatorcontrib>Li, Xiao-Dan</creatorcontrib><creatorcontrib>Ye, Han-Qing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - 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Although there are a few drugs approved for clinical treatment to combat SARS-CoV-2 infection currently, the severity of the ongoing global pandemic still urges the efforts to discover new antiviral compounds. As the viral spike (S) protein plays a key role in mediating virus entry, it becomes a potential target for the design of antiviral drugs against COVID-19. Here, we tested the antiviral activity of berbamine hydrochloride, a bis-benzylisoquinoline alkaloid, against SARS-CoV-2 infection. We found that berbamine hydrochloride could efficiently inhibit SARS-CoV-2 infection in different cell lines. Further experiments showed berbamine hydrochloride inhibits SARS-CoV-2 infection by targeting the viral entry into host cells. Moreover, berbamine hydrochloride and other bis-benzylisoquinoline alkaloids could potently inhibit S-mediated cell-cell fusion. Furthermore, molecular docking results implied that the berbamine hydrochloride could bind to the post fusion core of SARS-CoV-2 S2 subunit. Therefore, berbamine hydrochloride may represent a potential efficient antiviral agent against SARS-CoV-2 infection.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35468133</pmid><doi>10.1371/journal.pntd.0010363</doi><orcidid>https://orcid.org/0000-0001-7770-4071</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1935-2735 |
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| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Public Library of Science (PLoS); PubMed Central |
| subjects | Alkaloids Antiviral activity Antiviral agents Antiviral Agents - pharmacology Benzylisoquinolines - pharmacology Biology and life sciences Cell fusion Cell lines Coronaviruses COVID-19 COVID-19 - drug therapy Cytotoxicity Disease transmission Dosage and administration Drug development Drugs Experiments FDA approval Fusion protein Genomes Health Humans Infections Laboratories Medicine and health sciences Membrane Fusion Membrane proteins Molecular docking Molecular Docking Simulation Pandemics Physical Sciences Proteins Public health Research and Analysis Methods RNA polymerase SARS-CoV-2 Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus Tropical diseases Viral diseases Virology Virus Internalization Viruses |
| title | Berbamine hydrochloride potently inhibits SARS-CoV-2 infection by blocking S protein-mediated membrane fusion |
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