Article: Impairment of SARS-CoV-2 spike glycoprotein maturation and fusion activity by nitazoxanide: an effect independent of spike variants emergence
Cellular and molecular life sciences. 2022 May, v. 79, no. 5
2022
Abstract: SARS-CoV-2, the causative agent of COVID-19, has caused an unprecedented global health crisis. The SARS-CoV-2 spike, a surface-anchored trimeric class-I fusion glycoprotein essential for viral entry, represents a key target for developing vaccines and ... ...
Abstract | SARS-CoV-2, the causative agent of COVID-19, has caused an unprecedented global health crisis. The SARS-CoV-2 spike, a surface-anchored trimeric class-I fusion glycoprotein essential for viral entry, represents a key target for developing vaccines and therapeutics capable of blocking virus invasion. The emergence of SARS-CoV-2 spike variants that facilitate virus spread and may affect vaccine efficacy highlights the need to identify novel antiviral strategies for COVID-19 therapy. Here, we demonstrate that nitazoxanide, an antiprotozoal agent with recognized broad-spectrum antiviral activity, interferes with SARS-CoV-2 spike maturation, hampering its terminal glycosylation at an endoglycosidase H-sensitive stage. Engineering multiple SARS-CoV-2 variant-pseudoviruses and utilizing quantitative cell–cell fusion assays, we show that nitazoxanide-induced spike modifications hinder progeny virion infectivity as well as spike-driven pulmonary cell–cell fusion, a critical feature of COVID-19 pathology. Nitazoxanide, being equally effective against the ancestral SARS-CoV-2 Wuhan-spike and different emerging variants, including the Delta variant of concern, may represent a useful tool in the fight against COVID-19 infections. |
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Keywords | COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; antiviral properties ; etiological agents ; glycoproteins ; glycosylation ; pathogenicity ; progeny ; therapeutics ; vaccines ; virion ; viruses |
Language | English |
Dates of publication | 2022-05 |
Size | p. 227. |
Publishing place | Springer International Publishing |
Document type | Article |
ZDB-ID | 1358415-7 |
ISSN | 1420-9071 ; 1420-682X |
ISSN (online) | 1420-9071 |
ISSN | 1420-682X |
DOI | 10.1007/s00018-022-04246-w |
Database | NAL-Catalogue (AGRICOLA) |
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