Structural and functional impact by SARS-CoV-2 Omicron spike mutations.

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.

Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant.

The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has outcompeted previously prevalent variants and become a dominant strain worldwide. We report the structure, function, and antigenicity of its full-length spike (S) trimer as well as those of the Gamma and Kappa variants, and compare their characteristics with the G614, Alpha, and Beta variants. Delta S can fuse membranes more efficiently at low levels of cellular receptor angiotensin converting enzyme 2 (ACE2), and its pseudotyped viruses infect target cells substantially faster than the other five variants, possibly accounting for its heightened transmissibility. Each variant shows different rearrangement of the antigenic surface of the amino-terminal domain of the S protein but only makes produces changes in the receptor binding domain (RBD), making the RBD a better target for therapeutic antibodies.

Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants.

Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the dominant circulating strains in the COVID-19 pandemic. We report here cryo-electron microscopy structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Amino acid substitutions in the B.1.1.7 protein increase both the accessibility of its receptor binding domain and the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement may account for the increased transmissibility. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein, making it resistant to some potent neutralizing antibodies. These findings provide structural details on how SARS-CoV-2 has evolved to enhance viral fitness and immune evasion.

Public awareness and acceptance of COVID-19 vaccine: An online cross-sectional survey, conducted in the first phase of vaccination drive in India (preprint)

The context-specific, complex issue of ‘vaccine hesitancy’ is explicated in terms of delay or refusal of vaccination despite the availability of vaccine services. Although eleven million beneficiaries were administered the COVID-19 vaccine in India from 16th January 2021 till 20th February 2021, however, proportionately a low turnout has been registered in various parts of the country, possibly attributable to hesitance/apprehension towards the current vaccination. In this backdrop, we report the response (collected between Feb 1, 2021 and Feb 15, 2021) of 358 voluntary respondents who participated in an online questionnaire-based pan-India survey, executed to assess their knowledge and acceptance towards the current COVID-19 vaccination program in its first phase. The survey questionnaire consisted of demographic characteristics of the respondents and queries pertaining to knowledge (7 items) and acceptance (3 items). The overall correct rate and the average knowledge score of the participants were 78 % and 5.46 ± 1.4/7 respectively. The acceptance score was 3.50 ± 1.6/5 while 70 % of participants agreed against the 20 % of respondents who neither agreed nor disagreed to take the vaccine. Around 66 % believed that the vaccines, currently being administered in India are safe. Fear about possible side effects (44 %) and inadequacy of comprehensive clinical trial data (29 %), seemed to be the major players in fortifying the vaccine hesitancy among the respondents, exhibiting negative acceptance. Although maximum respondents demonstrated a good level of knowledge (82%) and acceptance (88%), significant differences were observed among some demographic variables. In general, a positive correlation was observed between knowledge and acceptance against a negative correlation, observed in specific provinces. Despite the good acceptance and knowledge, a considerable fraction of the participants (30%) expressed hesitancy. Counselling, mobilization, and feedback from vaccinated individuals about safety should be encouraged. However, due to the limited sample size, we must be cautious when generalizing these findings. Nevertheless, the major elucidations of this study may be utilized in planning vaccination campaigns in further phases.