The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India1–5. Since then, it has become dominant in some regions of India and in the UK, and has spread to many other countries6. The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), which contain diverse mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein that may increase the immune evasion potential of these variants. B.1.617.2—also termed the Delta variant—is believed to spread faster than other variants. Here we isolated an infectious strain of the Delta variant from an individual with COVID-19 who had returned to France from India. We examined the sensitivity of this strain to monoclonal antibodies and to antibodies present in sera from individuals who had recovered from COVID-19 (hereafter referred to as convalescent individuals) or who had received a COVID-19 vaccine, and then compared this strain with other strains of SARS-CoV-2. The Delta variant was resistant to neutralization by some anti-NTD and anti-RBD monoclonal antibodies, including bamlanivimab, and these antibodies showed impaired binding to the spike protein. Sera collected from convalescent individuals up to 12 months after the onset of symptoms were fourfold less potent against the Delta variant relative to the Alpha variant (B.1.1.7). Sera from individuals who had received one dose of the Pfizer or the AstraZeneca vaccine had a barely discernible inhibitory effect on the Delta variant. Administration of two doses of the vaccine generated a neutralizing response in 95% of individuals, with titres three- to fivefold lower against the Delta variant than against the Alpha variant. Thus, the spread of the Delta variant is associated with an escape from antibodies that target non-RBD and RBD epitopes of the spike protein. The SARS-CoV-2 Delta variant partially evades neutralization by several monoclonal antibodies and by sera from individuals who have had COVID-19, but two doses of anti-COVID-19 vaccines still generate a strong neutralizing response.

/pdf/reduced-sensitivity-of-sars-cov-2-variant-delta-to-antibody-4vfjtit4rl.pdf

Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization.

SARS-CoV-2 501Y.V2 (B.1.351), a novel lineage of coronavirus causing COVID-19, contains substitutions in two immunodominant domains of the spike protein. Here, we show that pseudovirus expressing 501Y.V2 spike protein completely escapes three classes of therapeutically relevant antibodies. This pseudovirus also exhibits substantial to complete escape from neutralization, but not binding, by convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and foreshadows reduced efficacy of spike-based vaccines.

https://biorxiv.org/content/10.1101/2021.01.18.427166v1.full.pdf

SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma

Emerging strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, that show increased transmission fitness and/or immune evasion are classified as “variants of concern” (VOCs). Recently, a SARS-CoV-2 variant first identified in November 2021 in South Africa has been recognized as a fifth VOC, termed “Omicron.” What makes this VOC so alarming is the high number of changes, especially in the viral Spike protein, and accumulating evidence for increased transmission efficiency and escape from neutralizing antibodies. ABSTRACT Emerging strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, that show increased transmission fitness and/or immune evasion are classified as “variants of concern” (VOCs). Recently, a SARS-CoV-2 variant first identified in November 2021 in South Africa has been recognized as a fifth VOC, termed “Omicron.” What makes this VOC so alarming is the high number of changes, especially in the viral Spike protein, and accumulating evidence for increased transmission efficiency and escape from neutralizing antibodies. In an amazingly short time, the Omicron VOC has outcompeted the previously dominating Delta VOC. However, it seems that the Omicron VOC is overall less pathogenic than other SARS-CoV-2 VOCs. Here, we provide an overview of the mutations in the Omicron genome and the resulting changes in viral proteins compared to other SARS-CoV-2 strains and discuss their potential functional consequences.

Omicron: What Makes the Latest SARS-CoV-2 Variant of Concern So Concerning?

Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

Introduction: The current SARS-CoV-2 pandemic urgently demands for both prevention and treatment strategies. RNA-dependent RNA-polymerase (RdRp), which has no counterpart in human cells, is an exce...

https://www.tandfonline.com/doi/pdf/10.1080/13543776.2021.1880568

SARS-CoV-2 RNA dependent RNA polymerase as a therapeutic target for COVID-19

10045 Background: Approximately 10% of childhood solid tumors occur in individuals with a cancer genetic predisposition. Identifying cancer predisposition permits interventions for prevention and early detection of future cancers in the child and their affected family members and may have other important medical care implications. The American Society of Clinical Oncology (ASCO) guidelines recommend reviewing family history (FHx) to identify high-risk patients who should be offered genetic testing. To our knowledge, adherence to ASCO guidelines by pediatric oncology providers (POPs) has not been studied. Methods: Retrospective chart review of solid tumor patients <18 years of age referred for genetic counseling 1/1/2017-1/31/2019. POP and genetic counselor (GC) FHx documentation was assessed for adherence with the ASCO minimum quality metrics: 2 generation pedigree, patient ethnicity, cancer genetic testing results in relatives (GTRR), and cancer type, age at diagnosis, and lineage (maternal/paternal) for each relative with cancer (RWC). Comparisons of FHx quality between POPs and GCs were evaluated with 1-sided t-tests. Ethnicity was considered assessed if both maternal and paternal ethnicities were documented. GTRR was considered assessed if the results of all relatives who had undergone genetic testing were noted. Cancer type, age at diagnosis, and lineage were considered assessed if they were checked for all RWCs. Whether or not the child underwent genetic testing and their testing results were also documented. Results: Of 129 eligible patients, 102 underwent germline genetic testing. Twelve (12%) had pathogenic alterations in cancer predisposition genes. The POP failed to document FHx in 20 patients (16%), including 2 with pathogenic germline alterations. The POP missed first/second degree RWCs in 32 of 88 patients with RWCs (36%). GCs achieved >99% on each of the 6 ASCO quality metrics, whereas POPs performed significantly more poorly (Table). In patients with RWCs, GCs achieved all 6 metrics in more cases than POPs (99% vs. 3%, p<0.001). Conclusions: POPs performed significantly worse than GCs in documenting family history compliant with ASCO minimum family history guidelines, raising concern for missed genetic cancer predisposition syndrome diagnoses in those not referred to a GC. Routine referral of pediatric solid tumor patients to a GC for family history review and interventions to improve the quality of family history taking by POPs may improve germline cancer predisposition detection, improving care of both patients and their affected family members. [Table: see text]

Quality of cancer family history taking in pediatric solid tumor patients.

Background: To prioritize the development of antiviral compounds, it is necessary to compare their relative preclinical activity and clinical efficacy. Methods: We reviewed in vitro, animal model, and clinical studies of candidate anti-coronavirus compounds and placed extracted data in an online relational database. Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. SARS-CoV-2, SARS-CoV, and MERS-CoV account for 85% of the data. Approximately 75% of experiments involved compounds with known or likely mechanisms of action, including monoclonal antibodies and receptor binding inhibitors (21%), viral protease inhibitors (17%), miscellaneous host-acting inhibitors (10%), polymerase inhibitors (9%), interferons (7%), fusion inhibitors (5%), and host protease inhibitors (5%). Of 975 compounds with known or likely mechanism, 135 (14%) are licensed in the U.S. for other indications, 197 (20%) are licensed outside the U.S. or are in human trials, and 595 (61%) are pre-clinical investigational compounds. Conclusion: CoV-RDB facilitates comparisons between different candidate antiviral compounds, thereby helping scientists, clinical investigators, public health officials, and funding agencies prioritize the most promising compounds and repurposed drugs for further development.

https://www.mdpi.com/1999-4915/12/9/1006/pdf

Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds.

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Quality of cancer family history taking in pediatric solid tumor patients.

Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds.