key: cord-0905488-y5xsaoyo authors: Ranjan, Prashant; Neha,; Devi, Chandra; Das, Parimal title: Bioinformatics analysis of SARS-CoV-2 RBD mutant variants and insights into antibody and ACE2 receptor binding date: 2021-04-26 journal: bioRxiv DOI: 10.1101/2021.04.03.438113 sha: 1b90570bb1e68563fef65a409d7d837f19d19e34 doc_id: 905488 cord_uid: y5xsaoyo Prevailing COVID-19 vaccines are based on the spike protein of earlier SARS-CoV-2 strain that emerged in Wuhan, China. The continuously evolving nature of SARS-CoV-2 resulting emergence of new variants raises the risk of immune absconds. During the last few months, several RBD (receptor-binding domain) variants have been reported to affect the vaccine efficacy considerably. Soon after reporting of a new double mutant variant (L452R & E484Q) in India, the country facing a deadlier second wave of infections which prompts researchers to suspects this variant to be accountable. To address the relevant concerns about this new variant affecting vaccine efficacy, we performed molecular simulation dynamics based structural analysis of spike protein of double mutant (L452R & E484Q) along with K417G variants and earlier reported RBD variants and found structural changes in RBD region after comparing with the wild type. Comparison of the binding affinity of the double mutant and earlier reported RBD variant for ACE2 (angiotensin 2 altered enzymes) receptor and CR3022 antibody with the wild-type strain revealed the lowest binding affinity of the double mutant for CR3022 among all other variants. These findings suggest that the newly emerged double mutant could significantly reduce the impact of the current vaccine which threatens the protective efficacy of current vaccine therapy. This new variant was found in >200 samples from Maharashtra only, which became the first hot spot region during the second national wave that started in the last few months. By around 7 April, Maharashtra alone accounted for more than half of the new cases filed in the country, convincing experts to doubt that the variant might be blamed. Approximately, more than half of the districts in Maharashtra now have a large no. of cases than the high rate in September. Nagpur, which has returned to lockdown, records 67 new cases over 100,000 people per day, more than thrice the statewide rate. These cases are doubling every 10 days. In India, over 180,000 new infections occurred in a 24-hour period in the previous week, taking the total number of cases to over 13.9 million. For better management of this second wave, we need to re-evaluate the threshold efficacy of the vaccine explore the functional aspects or potential efficacy of vaccine therapy currently Based on the up to date literature survey, we retrieved 28 different spike protein variants and out of these 28 variants, 12 variants belong to RBD region only. Here, we report RBD variants that affect the ability of CR3022 and ACE2 to bind with the SARS-CoV-2 RBD through insilico analysis. Crystalstructuresof spike protein (PDBID-7AD1), ACE2 (PDBID-6ACG) and antibody CR3022 (PDBID 6YLA) were retrieved from PDB RCSB (https://www.rcsb.org/). All water molecules and hetro-atoms were removed by using Discovery studio visualization software (BIOVIA 2020). (http://accelrys.com/products/collaborative-science/biovia-discoverystudio/visualization-download.php). Based on high similarity, 7AD1 (crystal structure of SARS-CoV-2) was selected as template for The equilibrium and the dynamic behavior of wild and mutant variants of RBD Spike protein was studied by using GROMACS (Hess, et al., 2008 To Continuing emerging variant of SARS-Cov-2 resulting compromised vaccine induced immunity. Figure2. 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