Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity

Jia, Yuping; Shen, Gangxu; Nguyen, Stephanie; Zhang, Yujuan; Huang, Ke; Ho, H.M.; W, Hor; Yang, Chorng-Horng; Bruning, John B.; C, Li; Wang, W

doi:10.1101/2020.04.09.034942

Cited by 101 publications

(113 citation statements)

References 45 publications

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“…Several reports 17,18 now suggest that there are multiple SARS-CoV-2 isolates with stable mutations in the spike S protein. SARS-CoV-2 mutations described one of these recent reports 17 (Table 1) demonstrates that these are either predicted to increase or decrease glycosylation at various sites in the in the spike S protein, and these may possibly account for differences in virulence. A stable mutation in the SARS-CoV-2 spike protein found in one report is predicted to bind ACE2 less tightly, predicting a decrease in virulence.…”

Section: Conflict Of Interest: Nonementioning

confidence: 99%

DC/L‐SIGNs of hope in the COVID‐19 pandemic

Brufsky

Lotze

2020

Journal of Medical Virology

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In a rapidly evolving pandemic such as COVID-19, theories which help unify disparate pre-clinical and clinical observations would be useful. The current pandemic and its pleotropic effects can be explained in part by interaction between SARS-CoV-2 spike protein S, the ACE2/L-SIGN/CD209 receptor on the type II alveolar cell of the lung, and the DC-SIGN receptor on the respiratory dendritic cell (DC) and associated endothelial cells. Infection of the DC by SARS-CoV-2 can potentially explain the exuberant distal immunopathology seen in In a mouse model of severe acute respiratory distress syndrome (SARS), the human disease most related to COVID-19 in clinical course, severe disease is correlated with slow kinetics of SARS-CoV viral clearance 1 . This is accompanied by delayed activation and transit of respiratory DCs to the draining lymph nodes with a deficient virus-specific T cell response 1 . In the SARS-CoV-2 infection, there is initial lymphopenia, and the lymphocyte count is predictive of disease severity and mortality 2 . Lymphocyte counts recover with viral clearance and disease resolution, with adaptive immune cells (CD3+ T cells) being especially important 2 . Such immune deficiency can in part be explained by viral infection and T-cell interaction with the respiratory DC.Early and central infection of tissue resident dendritic cells (DC) by the SARS-CoV-2 coronavirus explain some of the immunopathology of the COVID-19 pandemic. DC are richly abundant in the lung and responsive to viral infection 3 . RNA expression profiling studies demonstrate that human DC express the ACE2 receptor for SARS-CoV-2 4 . In COVID-19, T cell receptor (TCR) repertoires are dramatically reduced during the early onset of severe SARS-CoV-2 infection but recover during the convalescent stage 5 . Such reduction of T cells suggest acute wholesale apoptotic death with engagement of the TCR in the absence of costimulatory molecules, normally provided by DC 6 .DC also express DC-SIGN. DC-SIGN (dendritic cell-specific ICAM-3-grabbing nonintegrin) is a membrane receptor of a C-type lectin family expressed on DCs with a primary function of recognizing high mannose glycans present on other cellular receptors or pathogens 7 . With L-SIGN (CD209L, DC-SIGNR, or liver/lymph specific SIGN) expression, the other SIGN found in humans 8 , these mannose receptors are involved in virus capture and entry into cells 9 . L-SIGN is expressed on human type II alveolar cells, is associated with ACE2 10 , and can enhance ACE2 mediated binding and cellular entry of viral pseudotypes expressing the spike protein S of SARS-CoV 9 .Lentiviral pseudotyped viruses expressing SARS-CoV S protein require acidification of the endosome for viral entry 11 . DC-SIGN mediates binding of these pseudotyped vectors to human DC with uptake into the endosome, followed by polarization of the endosome and delivery of the virus in an "infectious synapse" 11 . This appears similar to an infectious synapse between infected DC and T cells that facilitates HIV infection mediated by...

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Section: Conflict Of Interest: Nonementioning

confidence: 99%

DC/L‐SIGNs of hope in the COVID‐19 pandemic

Brufsky

Lotze

2020

Journal of Medical Virology

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“…Additionally, some mutations modulating SARS-CoV-2 virulence have an impact on the glycosylation level of the spike. As an example, the D614G mutation, which increases virulence, has been reported as potentially increasing glycosylation at neighboring asparagine 616 (Brufsky and Lotze, 2020;Jia et al, 2020;Korber et al, 2020). A recent proteomic profiling study pointed to DC-SIGN as a mediator of genetic risk in COVID-19 (Katz et al, 2020) and finally it is of note that DC/L-SIGN expression is induced by proinflammatory cytokines such as IL-4, IL-6, IL-10 and IL-13, known to be overexpressed in severe SARS and COVID-19 cases (Lucas et al, 2020;Relloso and Puig-Kroger).…”

Section: Introductionmentioning

confidence: 99%

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

Thépaut

Luczkowiak

Vivès

et al. 2020

Preprint

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The efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in air mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. Thus, we described a mechanism potentiating viral capture and spreading of infection. Early involvement of APCs opens new avenues for understanding and treating the imbalanced innate immune response observed in COVID-19 pathogenesis.

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“…1b, see Methods for details). Preliminary reports on SARS-CoV-2 genome evolution indicate a similar trend 9 .…”

Section: Main Textmentioning

confidence: 78%

Prediction of the virus incubation period for COVID-19 and future outbreaks

Auslander

et al. 2020

Preprint

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A crucial factor in mitigating respiratory viral outbreaks is early determination of the duration of the incubation period and, accordingly, the required quarantine time for potentially exposed individuals. Here, we explore different genomic features of RNA viruses that correlate with the incubation times and provide a predictive model that accurately estimates the upper limit incubation time for diverse viruses including SARS-CoV-2, and thus, could help control future outbreaks.

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Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity

Cited by 101 publications

References 45 publications

DC/L‐SIGNs of hope in the COVID‐19 pandemic

DC/L‐SIGNs of hope in the COVID‐19 pandemic

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

Prediction of the virus incubation period for COVID-19 and future outbreaks

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