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Anti-Fungal Drug Anidulafungin Inhibits SARS-CoV-2 Spike-Induced Syncytia Formation by Targeting ACE2-Spike Protein Interaction.

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cam.issuedOnline2022-03-25
dc.contributor.authorAhamad, Shahzaib
dc.contributor.authorAli, Hashim
dc.contributor.authorSecco, Ilaria
dc.contributor.authorGiacca, Mauro
dc.contributor.authorGupta, Dinesh
dc.contributor.orcidAli, Hashim [0000-0002-5056-845X]
dc.date.accessioned2022-04-08T09:00:17Z
dc.date.available2022-04-08T09:00:17Z
dc.date.issued2022
dc.date.submitted2022-01-31
dc.date.updated2022-04-08T09:00:17Z
dc.description.abstractDrug repositioning continues to be the most effective, practicable possibility to treat COVID-19 patients. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters target cells by binding to the ACE2 receptor via its spike (S) glycoprotein. We used molecular docking-based virtual screening approaches to categorize potential antagonists, halting ACE2-spike interactions by utilizing 450 FDA-approved chemical compounds. Three drug candidates (i.e., anidulafungin, lopinavir, and indinavir) were selected, which show high binding affinity toward the ACE2 receptor. The conformational stability of selected docked complexes was analyzed through molecular dynamics (MD) simulations. The MD simulation trajectories were assessed and monitored for ACE2 deviation, residue fluctuation, the radius of gyration, solvent accessible surface area, and free energy landscapes. The inhibitory activities of the selected compounds were eventually tested in-vitro using Vero and HEK-ACE2 cells. Interestingly, besides inhibiting SARS-CoV-2 S glycoprotein induced syncytia formation, anidulafungin and lopinavir also blocked S-pseudotyped particle entry into target cells. Altogether, anidulafungin and lopinavir are ranked the most effective among all the tested drugs against ACE2 receptor-S glycoprotein interaction. Based on these findings, we propose that anidulafungin is a novel potential drug targeting ACE2, which warrants further investigation for COVID-19 treatment.
dc.identifier.doi10.17863/CAM.83343
dc.identifier.eissn1664-8021
dc.identifier.issn1664-8021
dc.identifier.other866474
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/335908
dc.languageen
dc.language.isoeng
dc.publisherFrontiers Media SA
dc.publisher.urlhttp://dx.doi.org/10.3389/fgene.2022.866474
dc.subjectACE2
dc.subjectCOVID-19
dc.subjectMD simulations
dc.subjectSARS-CoV-2
dc.subjectanidulafungin
dc.subjectsyncytia
dc.subjectvirtual screening
dc.titleAnti-Fungal Drug Anidulafungin Inhibits SARS-CoV-2 Spike-Induced Syncytia Formation by Targeting ACE2-Spike Protein Interaction.
dc.typeArticle
dcterms.dateAccepted2022-03-01
prism.publicationNameFront Genet
prism.volume13
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.3389/fgene.2022.866474

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