A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike

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Deep mutational learning predicts ACE2 binding and antibody escape to combinatorial mutations in the SARS-CoV-2 receptor-binding domain

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Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition

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Receptor binding,immune escape,and protein stability direct the natural selection of SARS-CoV-2 variants

Emergence of new severe acute respiratory syndrome coronavirus 2 variants has raised concerns related to the effectiveness of vaccines and antibody therapeutics developed against the unmutated wildtype virus. Here, we examined the effect of the 12 most commonly occurring mutations in the receptor-binding domain of the spike protein on its expression, stability, activity, and antibody escape potential. Stability was measured using thermal denaturation, and the activity and antibody escape potential were measured using isothermal titration calorimetry in terms of binding to the human angiotensin-converting enzyme 2 and to neutralizing human antibody CC12.1, respectively. Our results show that mutants differ in their expression levels. Of the eight best-expressed mutants, two (N501Y and K417T/E484K/N501Y) showed stronger affinity to angiotensin-converting enzyme 2 compared with the wildtype, whereas four (Y453F, S477N, T478I, and S494P) had similar affinity and two (K417N and E484K) had weaker affinity than the wildtype. Compared with the wildtype, four mutants (K417N, Y453F, N501Y, and K417T/E484K/N501Y) had weaker affinity for the CC12.1 antibody, whereas two (S477N and S494P) had similar affinity, and two (T478I and E484K) had stronger affinity than the wildtype. Mutants also differ in their thermal stability, with the two least stable mutants showing reduced expression. Taken together, these results indicate that multiple factors contribute toward the natural selection of variants, and all these factors need to be considered to understand the evolution of the virus. In addition, since not all variants can escape a given neutralizing antibody, antibodies to treat new variants can be chosen based on the specific mutations in that variant.     

Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies

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Clinical practice of rapid antigen tests for SARS-CoV-2 Omicron variant: A single-center study in China

Responding to the fast-spreading SARS-CoV-2 Omicron variant, to improve screening efficiency, rapid antigen tests (RATs) were first added as a supplementary detection method in China in mid-March, 2022. What and how big a role RATs should play need to be supported by clinical data. Here, RAT performance and relevant factors in comparison with nucleic acid amplification tests (NAATs) were assessed in Omicron-infected inpatients. From the NAAT results, nasopharyngeal swabs (NPs) performed better than oropharyngeal swabs (OPs). RATs tested on NAAT positive NPs performed better than those with OP-positive samples. The RAT positivity rate was strongly associated with high levels of N and OFR1ab genes, especially in NPs where patients also had significantly longer hospital stays and shorter days from symptom onset to RAT testing. Self-performed RATs had a detection accuracy that was comparable to professionally performed RATs when the subjects were well guided. The antigen negative rate of the studied patients was 100% at discharge. These findings suggest that, in addition to a supplementary detection role, RATs can be an important strategy for evaluating the disease progression of Omicron-infected inpatients. This study provides important clinical data to support better rules regarding RATs under China's COVID-19 prevention and control policy.     

Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients

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SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies

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Functional map of SARS-CoV-2 3CL protease reveals tolerant and immutable sites

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Emergence,evolution, and vaccine production approaches of SARS-CoV-2 virus: Benefits of getting vaccinated and common questions

The emergence of coronavirus disease 2019 (COVID-19) pandemic in Wuhan city, China at the end of 2019 made it urgent to identify the origin of the causal pathogen and its molecular evolution, to appropriately design an effective vaccine. This study analyzes the evolutionary background of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or SARS-2) in accordance with its close relative SARS-CoV (SARS-1), which was emerged in 2002. A comparative genomic and proteomic study was conducted on SARS-2, SARS-1, and Middle East respiratory syndrome coronavirus (MERS), which was emerged in 2012. In silico analysis inferred the genetic variability among the tested viruses. The SARS-1 genome harbored 11 genes encoding 12 proteins, while SARS-2 genome contained only 10 genes encoding for 10 proteins. MERS genome contained 11 genes encoding 11 proteins. The analysis also revealed a slight variation in the whole genome size of SARS-2 comparing to its siblings resulting from sequential insertions and deletions (indels) throughout the viral genome particularly ORF1AB, spike, ORF10 and ORF8. The effective indels were observed in the gene encoding the spike protein that is responsible for viral attachment to the angiotensin-converting enzyme 2 (ACE2) cell receptor and initiating infection. These indels are responsible for the newly emerging COVID-19 variants αCoV, βCoV, γCoV and δCoV. Nowadays, few effective COVID-19 vaccines developed based on spike (S) glycoprotein were approved and become available worldwide. Currently available vaccines can relatively prevent the spread of COVID-19 and suppress the disease. The traditional (killed or attenuated virus vaccine and antibody-based vaccine) and innovated vaccine production technologies (RNA- and DNA-based vaccines and viral vectors) are summarized in this review. We finally highlight the most common questions related to COVID-19 disease and the benefits of getting vaccinated.