tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2023 Mar 7;120(10):e2214561120.
doi: 10.1073/pnas.2214561120. Epub 2023 Feb 28.
Cyanovirin-N binds to select SARS-CoV-2 spike oligosaccharides outside of the receptor binding domain and blocks infection by SARS-CoV-2
Jordana Muñoz-Basagoiti[SUP] 1 [/SUP], Fábio Luís Lima Monteiro[SUP] 2 [/SUP], Lauren R H Krumpe[SUP] 3 4 [/SUP], Victoria Armario-Najera[SUP] 5 [/SUP], Shilpa R Shenoy[SUP] 3 4 [/SUP], Daniel Perez-Zsolt[SUP] 1 [/SUP], Harrison James Westgarth[SUP] 2 [/SUP], Gemma Villorbina[SUP] 5 [/SUP], Larissa Maciel Bomfim[SUP] 2 [/SUP], Dàlia Raïch-Regué[SUP] 1 [/SUP], Lara Nogueras[SUP] 5 [/SUP], Curtis J Henrich[SUP] 3 4 [/SUP], Marçal Gallemí[SUP] 1 [/SUP], Filipe Romero Rebello Moreira[SUP] 2 [/SUP], Pascual Torres[SUP] 5 [/SUP], Jennifer Wilson[SUP] 3 4 [/SUP], Mirela D'arc[SUP] 6 [/SUP], Silvia Marfil[SUP] 1 [/SUP], Alice Laschuk Herlinger[SUP] 2 [/SUP], Edwards Pradenas[SUP] 1 [/SUP], Luiza Mendonça Higa[SUP] 2 [/SUP], Manuel Portero-Otin[SUP] 5 [/SUP], Benjamin Trinité[SUP] 1 [/SUP], Richard M Twyman[SUP] 7 [/SUP], Teresa Capell[SUP] 5 [/SUP], Amilcar Tanuri[SUP] 2 [/SUP], Julià Blanco[SUP] 1 8 9 10 [/SUP], Nuria Izquierdo-Useros[SUP] 1 8 9 [/SUP], Elibio L Rech[SUP] 11 [/SUP], Paul Christou[SUP] 5 12 [/SUP], Barry R O'Keefe[SUP] 3 13 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped positive stranded RNA virus which has caused the recent deadly pandemic called COVID-19. The SARS-CoV-2 virion is coated with a heavily glycosylated Spike glycoprotein which is responsible for attachment and entry into target cells. One, as yet unexploited strategy for preventing SARS-CoV-2 infections, is the targeting of the glycans on Spike. Lectins are carbohydrate-binding proteins produced by plants, algae, and cyanobacteria. Some lectins can neutralize enveloped viruses displaying external glycoproteins, offering an alternative therapeutic approach for the prevention of infection with virulent β-coronaviruses, such as SARS-CoV-2. Here we show that the cyanobacterial lectin cyanovirin-N (CV-N) can selectively target SARS-CoV-2 Spike oligosaccharides and inhibit SARS-CoV-2 infection in vitro and in vivo. CV-N neutralizes Delta and Omicron variants in vitro better than earlier circulating viral variants. CV-N binds selectively to Spike with a Kd as low as 15 nM and a stoichiometry of 2 CV-N: 1 Spike but does not bind to the receptor binding domain (RBD). Further mapping of CV-N binding sites on Spike shows that select high-mannose oligosaccharides in the S1 domain of Spike are targeted by CV-N. CV-N also reduced viral loads in the nares and lungs in vivo to protect hamsters against a lethal viral challenge. In summary, we present an anti-coronavirus agent that works by an unexploited mechanism and prevents infection by a broad range of SARS-CoV-2 strains.
Keywords: SARS-CoV-2; antiviral; lectin; spike glycoprotein.
. 2023 Mar 7;120(10):e2214561120.
doi: 10.1073/pnas.2214561120. Epub 2023 Feb 28.
Cyanovirin-N binds to select SARS-CoV-2 spike oligosaccharides outside of the receptor binding domain and blocks infection by SARS-CoV-2
Jordana Muñoz-Basagoiti[SUP] 1 [/SUP], Fábio Luís Lima Monteiro[SUP] 2 [/SUP], Lauren R H Krumpe[SUP] 3 4 [/SUP], Victoria Armario-Najera[SUP] 5 [/SUP], Shilpa R Shenoy[SUP] 3 4 [/SUP], Daniel Perez-Zsolt[SUP] 1 [/SUP], Harrison James Westgarth[SUP] 2 [/SUP], Gemma Villorbina[SUP] 5 [/SUP], Larissa Maciel Bomfim[SUP] 2 [/SUP], Dàlia Raïch-Regué[SUP] 1 [/SUP], Lara Nogueras[SUP] 5 [/SUP], Curtis J Henrich[SUP] 3 4 [/SUP], Marçal Gallemí[SUP] 1 [/SUP], Filipe Romero Rebello Moreira[SUP] 2 [/SUP], Pascual Torres[SUP] 5 [/SUP], Jennifer Wilson[SUP] 3 4 [/SUP], Mirela D'arc[SUP] 6 [/SUP], Silvia Marfil[SUP] 1 [/SUP], Alice Laschuk Herlinger[SUP] 2 [/SUP], Edwards Pradenas[SUP] 1 [/SUP], Luiza Mendonça Higa[SUP] 2 [/SUP], Manuel Portero-Otin[SUP] 5 [/SUP], Benjamin Trinité[SUP] 1 [/SUP], Richard M Twyman[SUP] 7 [/SUP], Teresa Capell[SUP] 5 [/SUP], Amilcar Tanuri[SUP] 2 [/SUP], Julià Blanco[SUP] 1 8 9 10 [/SUP], Nuria Izquierdo-Useros[SUP] 1 8 9 [/SUP], Elibio L Rech[SUP] 11 [/SUP], Paul Christou[SUP] 5 12 [/SUP], Barry R O'Keefe[SUP] 3 13 [/SUP]
Affiliations
- PMID: 36853940
- DOI: 10.1073/pnas.2214561120
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped positive stranded RNA virus which has caused the recent deadly pandemic called COVID-19. The SARS-CoV-2 virion is coated with a heavily glycosylated Spike glycoprotein which is responsible for attachment and entry into target cells. One, as yet unexploited strategy for preventing SARS-CoV-2 infections, is the targeting of the glycans on Spike. Lectins are carbohydrate-binding proteins produced by plants, algae, and cyanobacteria. Some lectins can neutralize enveloped viruses displaying external glycoproteins, offering an alternative therapeutic approach for the prevention of infection with virulent β-coronaviruses, such as SARS-CoV-2. Here we show that the cyanobacterial lectin cyanovirin-N (CV-N) can selectively target SARS-CoV-2 Spike oligosaccharides and inhibit SARS-CoV-2 infection in vitro and in vivo. CV-N neutralizes Delta and Omicron variants in vitro better than earlier circulating viral variants. CV-N binds selectively to Spike with a Kd as low as 15 nM and a stoichiometry of 2 CV-N: 1 Spike but does not bind to the receptor binding domain (RBD). Further mapping of CV-N binding sites on Spike shows that select high-mannose oligosaccharides in the S1 domain of Spike are targeted by CV-N. CV-N also reduced viral loads in the nares and lungs in vivo to protect hamsters against a lethal viral challenge. In summary, we present an anti-coronavirus agent that works by an unexploited mechanism and prevents infection by a broad range of SARS-CoV-2 strains.
Keywords: SARS-CoV-2; antiviral; lectin; spike glycoprotein.