Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.

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Abstract

Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor-binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.

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Virological assessment of hospitalized patients with COVID-2019

Roman Wölfel, Victor M Corman, Wolfgang Guggemos … (2020)

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.

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Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

Renhong Yan, Yuanyuan Zhang, Yaning Li … (2020)

How SARS-CoV-2 binds to human cells Scientists are racing to learn the secrets of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), which is the cause of the pandemic disease COVID-19. The first step in viral entry is the binding of the viral trimeric spike protein to the human receptor angiotensin-converting enzyme 2 (ACE2). Yan et al. present the structure of human ACE2 in complex with a membrane protein that it chaperones, B0AT1. In the context of this complex, ACE2 is a dimer. A further structure shows how the receptor binding domain of SARS-CoV-2 interacts with ACE2 and suggests that it is possible that two trimeric spike proteins bind to an ACE2 dimer. The structures provide a basis for the development of therapeutics targeting this crucial interaction. Science, this issue p. 1444

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Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

B Korber, W.M. Fischer, S. Gnanakaran … (2020)

Summary A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.

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Journal

Journal ID (iso-abbrev): Elife

Title: eLife

Publisher: eLife Sciences Publications, Ltd

ISSN (Electronic): 2050-084X

ISSN (Print): 2050-084X

Publication date (Electronic): October 28 2020

Volume: 9

Affiliations

[1 ] Laboratory of Retrovirology, The Rockefeller University, New York, United States.

[2 ] Laboratory of Molecular Immunology The Rockefeller University, New York, United States.

[3 ] Laboratory of Virology and Infectious Disease The Rockefeller University, New York, United States.

[4 ] Lindsley F. Kimball Research Institute, New York Blood Center, New York, United States.

[5 ] Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.

[6 ] Howard Hughes Medical Institute, The Rockefeller University, New York, United States.

Article

Publisher Item ID: 61312

DOI: 10.7554/eLife.61312

PMC ID: 7723407

PubMed ID: 33112236

SO-VID: 3d65f667-9d4f-4e22-9c49-786b9b70b793

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Keywords: COVID19,SARS-CoV-2,VSV,antibody,immunology,infectious disease,inflammation,microbiology,virus

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Keywords: COVID19, SARS-CoV-2, VSV, antibody, immunology, infectious disease, inflammation, microbiology, virus

Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.

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Novel Coronavirus Disease COVID-19

Most cited references 54

Virological assessment of hospitalized patients with COVID-2019

Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

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