ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by first engaging its cellular receptor angiotensin converting enzyme 2 (ACE2) to induce conformational changes in the virus-encoded spike protein and fusion between the viral and target cell membranes. We report here that certain monoclonal neutralizing antibodies against distinct epitopic regions of the receptor-binding domain of the spike can replace ACE2 to serve as a receptor and efficiently support membrane fusion and viral infectivity. These receptor-like antibodies can function in the form of a complex of their soluble immunoglobulin G with Fc-gamma receptor I, a chimera of their antigen-binding fragment with the transmembrane domain of ACE2 or a membrane-bound B cell receptor, indicating that ACE2 and its specific interactions with the spike protein are dispensable for SARS-CoV-2 entry. These results suggest that antibody responses against SARS-CoV-2 may expand the viral tropism to otherwise nonpermissive cell types; they have important implications for viral transmission and pathogenesis.
Subject(s)
Severe Acute Respiratory SyndromeABSTRACT
Wavelet transform is a widespread and effective method in seismic waveform analysis and processing. Choosing a suitable wavelet has also aroused many scholars’ research interest and produced many effective strategies. However, with the convenience of seismic data acquisition, the existing wavelet selection methods are unsuitable for the big dataset. Therefore, we proposed a novel wavelet selection method considering the big dataset for seismic signal intelligent processing. The relevance r is calculated using the seismic waveform’s correlation coefficient and variance contribution rate. Then values of r are calculated from all seismic signals in the dataset to form a set. Furthermore, with a mean value μ and variance value σ2 of that set, we define the decomposition stability w as μ/σ2. Then, the wavelet that maximizes w for this dataset is considered to be the optimal wavelet. We applied this method in automatic mining-induced seismic signal classification and automatic seismic P arrival picking. In classification experiments, the mean accuracy is 93.13% using the selected wavelet, 2.22% more accurate than other wavelets generated. Additionally, in the picking experiments, the mean picking error is 0.59 s using the selected wavelet, but is 0.71 s using others. Moreover, the wavelet packet decomposition level does not affect the selection of wavelets. These results indicate that our method can really enhance the intelligent processing of seismic signals.
ABSTRACT
The Omicron subvariant BA.2 has become the dominant circulating strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in many countries. We have characterized structural, functional and antigenic properties of the full-length BA.2 spike (S) protein and compared replication of the authentic virus in cell culture and animal model with previously prevalent variants. BA.2 S can fuse membranes more efficiently than Omicron BA.1, mainly due to lack of a BA.1-specific mutation that may retard the receptor engagement, but still less efficiently than other variants. Both BA.1 and BA.2 viruses replicated substantially faster in animal lung than the parental strain in the absence of pre-existing immunity, possibly explaining the heightened transmissibility despite their functionally compromised spikes. As in BA.1, mutations in the BA.2 S remodel its antigenic surfaces leading to strong resistance to neutralizing antibodies. These results suggest that both immune evasion and replicative advantage may contribute to the heightened transmissibility for the Omicron subvariants.
Subject(s)
Coronavirus InfectionsABSTRACT
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), bearing an unusually high number of mutations, has become a dominant strain in many countries within several weeks. We report here structural, functional and antigenic properties of its full-length spike (S) protein with a native sequence in comparison with those of previously prevalent variants. Omicron S requires a substantially higher level of host receptor ACE2 for efficient membrane fusion than other variants, possibly explaining its unexpected cellular tropism. Mutations not only remodel the antigenic structure of the N-terminal domain of the S protein, but also alter the surface of the receptor-binding domain in a way not seen in other variants, consistent with its remarkable resistance to neutralizing antibodies. These results suggest that Omicron S has acquired an extraordinary ability to evade host immunity by excessive mutations, which also compromise its fusogenic capability.