The Omicron (B.1.1.529) variant of SARS-CoV-2 binds to the hACE2 receptor more strongly and escapes the antibody response: Insights from structural and simulation data.

As SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) continues to inflict chaos globally, a new variant officially known as B.1.1.529 was reported in South Africa and was found to harbor 30 mutations in the spike protein. It is too early to speculate on transmission and hospitalizations. Hence, more analyses are required, particularly to connect the genomic patterns to the phenotypic attributes to reveal the binding differences and antibody response for this variant, which can then be used for therapeutic interventions. Given the urgency of the required analysis and data on the B.1.1.529 variant, we have performed a detailed investigation to provide an understanding of the impact of these novel mutations on the structure, function, and binding of RBD to hACE2 and mAb to the NTD of the spike protein. The differences in the binding pattern between the wild type and B.1.1.529 variant complexes revealed that the key substitutions Asn417, Ser446, Arg493, and Arg498 in the B.1.1.529 RBD caused additional interactions with hACE2 and the loss of key residues in the B.1.1.529 NTD resulted in decreased interactions with three CDR regions (1-3) in the mAb. Further investigation revealed that B.1.1.529 displayed a stable dynamic that follows a global stability trend. In addition, the dissociation constant (KD), hydrogen bonding analysis, and binding free energy calculations further validated the findings. Hydrogen bonding analysis demonstrated that significant hydrogen bonding reprogramming took place, which revealed key differences in the binding. The total binding free energy using MM/GBSA and MM/PBSA further validated the docking results and demonstrated significant variations in the binding. This study is the first to provide a basis for the higher infectivity of the new SARS-CoV-2 variants and provides a strong impetus for the development of novel drugs against them.

Incidence of Acute Endophthalmitis After Intravitreal Bevacizumab Injection at a Tertiary Care Hospital in Lahore.

OBJECTIVE: We aimed to assess the incidence, management, and visual outcome of acute endophthalmitis in patients following intravitreal bevacizumab injection in a tertiary care setup. It was a prospective and single-center database study. PATIENTS AND METHODS: Patients receiving intravitreal bevacizumab injections for various retinal vascular diseases from January 2019 to September 2020. The study was carried out at the Institute of Ophthalmology, Mayo Hospital, Lahore over a period of 21 months. Preformed bevacizumab injections were administered intravitreally on patients of various retinal vascular diseases under strict aseptic measures and by following the standard guidelines. The patients were put on follow-ups for a duration of four weeks to see any signs of acute endophthalmitis. RESULTS: A total of 3051 injections were administered in 1104 eyes of 743 patients during the above-mentioned study period. The incidence of endophthalmitis was found to be 0.0328% (1/3051). The patient, who developed endophthalmitis, was treated with topical and intravitreal antibiotics followed by vitrectomy that resulted in clinically significant improvement in vision. CONCLUSION: Incidence of acute endophthalmitis following intravitreal bevacizumab injection was low and could be prevented by taking strict aseptic measures during administration.