PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity

He, Sijia; Waheed, Abdül; Hetrick, Brian; Dabbagh, Deemah; Akhrymuk, Ivan; Kehn-Hall, Kylene; Freed, Eric O.; Wu, Yuntao

doi:10.1101/2020.05.01.073387

Cited by 14 publications

(22 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that overexpression of IFITM1 and IFITM2 inhibits SARS-CoV-2 S-mediated VSVpp infection dose-dependently by up to two orders of magnitude, while IFITM3 was less effective ( Figure 1B). As control, we used PSGL-1 a broad-spectrum inhibitor of virus attachment (Fu et al, 2020) and confirmed that it prevents SARS-CoV-2 S-mediated infection (He et al, 2020). None of the IFITMs prevented VSV-G dependent entry ( Figure S1A).…”

Section: Ifitms Block Sars-cov-2 S-mediated Pseudoparticle Infectionmentioning

confidence: 77%

IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition

Bozzo

Nchioua

Volcic

et al. 2020

Preprint

View full text Add to dashboard Cite

Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) restrict numerous viral pathogens and are thought to prevent infection by severe acute respiratory syndrome coronaviruses (SARS-CoVs). However, most evidence comes from single-round pseudoparticle infection of cells artificially overexpressing IFITMs. Here, we confirmed that overexpression of IFITMs blocks pseudoparticle infections mediated by the Spike proteins of β-coronaviruses including pandemic SARS-CoV-2. In striking contrast, however, endogenous IFITM expression promoted genuine SARS-CoV-2 infection in human lung cells both in the presence and absence of interferon. IFITM2 was most critical for efficient entry of SARS-CoV-2 and enhanced virus production from Calu-3 cells by several orders of magnitude. IFITMs are expressed and further induced by interferons in the lung representing the primary site of SARS-CoV-2 infection as well as in other relevant tissues. Our finding that IFITMs enhance SARS-CoV-2 infection under conditions approximating the in vivo situation shows that they may promote viral invasion during COVID-19.

show abstract

Section: Ifitms Block Sars-cov-2 S-mediated Pseudoparticle Infectionmentioning

confidence: 77%

IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition

Bozzo

Nchioua

Volcic

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…However, a major issue for the VSV-based pseudovirus is the likely presence of residual VSV virus, which may result in high rates of false-positive results 27 . In addition, both VSV-and lentiviral-based pseudoviral particles contain structural components not native to the wild-type SARS-CoV-2, which may alter particle properties in receptor binding and responses to antibody neutralization 15 .…”

Section: Introductionmentioning

confidence: 99%

Development of a novel hybrid alphavirus-SARS-CoV-2 particle for rapid in vitro screening and quantification of neutralization antibodies, viral variants, and antiviral drugs

Hetrick

Chilin

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

SUMMARYTimely development of vaccines and antiviral drugs are critical to control the coronavirus disease 2019 (COVID-19) global pandemic 1–6. Current methods for validation of vaccine efficacy involve the use of pseudoviruses, such as the SARS-CoV-2 spike protein (S) pseudotyped lentivirus or vesicular stomatitis virus (VSV), to quantify neutralizing antibodies for blocking viral infection 7–14. The process of pseudovirus infection and quantification is time consuming and can take days to complete. In addition, pseudoviruses contain structural proteins not native to SARS-CoV-2, which may alter particle properties in receptor binding and responses to antibody neutralization 15. Here we describe the development of a new hybrid alphavirus-SARS-CoV-2 particle (Ha-CoV-2) for rapid screening and quantification of neutralization antibodies and antiviral drugs. Ha-CoV-2 is a non-replicating SARS-CoV-2 virus-like particle, composed of only SARS-CoV-2 structural proteins (S, M, N, and E) and a RNA genome derived from a fast expressing alphavirus vector 16. We demonstrate that Ha-CoV-2 can rapidly and robustly express reporter genes in target cells within 3-5 hours following viral entry. We further validate the Ha-CoV-2 system for rapid quantification of neutralization antibodies and antiviral drugs. In addition, we assembled a Ha-CoV-2 particle bearing the D614G mutant spike protein, and found that the mutation led to an approximately 200% increase in virion infectivity. These results demonstrate that Ha-CoV-2 can also be applied for rapid monitoring and quantification of viral mutations for effects on neutralizing antibodies induced by vaccines.

show abstract

“…To confirm these results, we repeated the infection using Vero E6 cells that endogenously express ACE2; Vero E6 supports productive SARS-CoV and SARS-CoV-2 infection and is commonly used in studies of coronaviruses (7). Given the low infectivity of pseudoviruses for Vero E6 in the absence of ACE2 overexpression (15,17,18), we also used a Luc reporter pseudovirus, in which the reporter expression is driven by HIV-1 LTR and Tat for higher reporter sensitivity and signal to noise ratio. As shown in Fig.…”

Section: Resultsmentioning

confidence: 91%

“…To discover potential anti-SARS-CoV-2 activities from TCMs, we screened extracts from approximately 40 TCMs, using a SARS-CoV-2 S protein pseudotyped lentivirus (14,15) and human lung A549(ACE2) target cells, in which the human ACE2 gene is over-expressed through lentiviral vector-mediated stable transduction. The lenti-pseudoviruses use either the green fluorescent protein (GFP) or luciferase (Luc) as the reporter, and were validated with a broadspectrum antiviral entry inhibitor, Arbidol (16), and human antiserum against SARS-CoV-2 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

A traditional medicine, Respiratory Detox Shot (RDS), inhibits the infection of SARS-CoV, SARS-CoV-2, and the Influenza A virusin vitro

Hetrick

Yu²,

Olanrewaju

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has resulted in the infection of over 60 million people and has caused over 1.4 million deaths as of December 2020 in more than 220 countries and territories. Currently, there is no effective treatment for COVID-19 to reduce mortality. We investigated the potential anti-coronavirus activities from an oral liquid of traditional medicine, Respiratory Detox Shot (RDS), which contains mostly herbal ingredients traditionally used to manage lung diseases. Here we report that RDS inhibited the infection of target cells by SARS-CoV and SARS-CoV-2 pseudoviruses, and by infectious wild-type SARS-CoV-2. We further demonstrated that RDS inhibits viral early infection steps. In addition, we found that RDS can also block the infection of target cells by Influenza A virus. These results suggest that RDS may broadly inhibit the infection of respiratory viruses.

show abstract

PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity

Cited by 14 publications

References 29 publications

IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition

IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition

Development of a novel hybrid alphavirus-SARS-CoV-2 particle for rapid in vitro screening and quantification of neutralization antibodies, viral variants, and antiviral drugs

A traditional medicine, Respiratory Detox Shot (RDS), inhibits the infection of SARS-CoV, SARS-CoV-2, and the Influenza A virusin vitro

Contact Info

Product

Resources

About